Guests: Dr. Charlie Elrod, Natural Biologics and Dr. Josh Jackman, Tropical Innovations/Sungkyunkwan University Today’s podcast tackles a big topic in the global swine industry - African Swine Fever Virus (ASFV). This virus has recently been reported in Thailand and continues to spread throughout the globe. While North America looks for any sign of ASFV, it continues to struggle with other lipid-enveloped viruses as well.
Guests: Dr. Charlie Elrod, Natural Biologics and Dr. Josh Jackman, Tropical Innovations/Sungkyunkwan University
Co-host: Dr. Ken Sanderson, Balchem
Today’s podcast tackles a big topic in the global swine industry - African Swine Fever Virus (ASFV). This virus has recently been reported in Thailand and continues to spread throughout the globe. While North America looks for any sign of ASFV, it continues to struggle with other lipid-enveloped viruses as well.
Dr. Josh Jackman states that over 80% of livestock and human population epidemics and pandemics are caused by lipid enveloped viruses, making it of huge economic significance. (14:31)
Dr. Charlie Elrod spoke of balancing the need for that macrophage recruitment and fighting the infection versus keeping them away. By tamping the virus down, or reducing the viral load that results in fewer macrophages getting infected, and fewer virus particles surviving in the mucosal environment, then you’ve improved. (27:02)
Dr. Josh Jackman explains that you need more than one hole in a virus membrane to become inactive or broken down. The structural damage is really important to break the structural integrity of the virus particle. Another mode to prevent infection is with compounds that prevent the viral membranes from fusing with cellular membranes. (33:09)
Dr. Charlie Elrod mentions that when feeding GML to sows, it does get into the milk circulation and can have a positive effect on piglets in the form of antimicrobial, antiviral and anti-inflammatory activity. Being able to mitigate risks to the most susceptible neonatal animals would be a good thing. (47:01)
Dr. Josh Jackman adds that there is an association between higher GML levels and reduced disease severity. The potential is huge because GML targets lipid enveloped viruses broadly. Since you can’t predict which virus will cause the next outbreak, GML is something that has the potential to be a first-line counter measure to the next pandemic. (57:27)
Dr. Charlie Elrod closes by saying there is a lot of potential discoveries out there.We need to continue exploring and bring in different sources of genetic mechanisms or more specific mechanisms like a flavonoid. This is really just the first chapter. (1:14:37)
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Scott Sorrell (00:00:07):
Good evening everyone. And welcome to the real science exchange. The pub cast we're leading scientists and industry professionals to meet over a few drinks to discuss the latest ideas and trends in animal agriculture. Tonight, we're taking on another big topic in the global swine industry and continuing a conversation started during one of our real science lecture series webinars. African swine fever virus has recently been reported in Thailand and continues to spread around the globe as North America braces for any sign of SD and continues to struggle with other lipid enveloped viruses, such as per and P E D V. We all look for ways to mitigate the impact. Hi, I'm Scott. Sorell is one of your hosts at the real science exchange tonight. We welcome Dr. Charlie Elrod from natural biologics. Charlie is an adjunct associate professor with Cornell University and president of natural biologics. Welcome to the exchange, Charlie. Thanks.
Dr. Charlie Elrod (00:01:01):
Glad to be here
Scott Sorrell (00:01:02):
Well, it's good to have you here. Can you tell us a little bit about natural biologics and then introduce your guest and that you brought to the pub tonight? Sure.
Dr. Charlie Elrod (00:01:12):
So natural biologics is a company I founded. It's about seven years old. We were founded basically as an animal health company, but want to tap into the power of natural compounds that are biologically active and can bring with them specific modes of action or activity perhaps it's antimicrobial, antiviral immune enhancing or whatever ever, and then combine those into products which address the specific challenges faced by typically livestock or production animals. So you know, we use several compounds from all around the world, naturally sourced and, and again, but those to work, to support you know, basically lower the level of challenge to the animals and then also reincrease their capacity to respond to a disease challenge.
Dr. Charlie Elrod (00:02:15):
We work hard, to validate these compounds and understand their modes of action and you know, then, publish our work and get it out there for the world to see so that you know, we have the credibility to bring these solutions to market. We also try to engage with the world's top experts in, in given fields to tap into the best expertise, to either help us validate or a, or even explore new areas that we may not be as familiar with. And it's along those lines that I became associated with Dr. Josh Jackman several years ago. And initially, I reached out to Josh. I was on the planning committee for one of the discovery conferences on natural bioactive. And I had recently read a review of Josh's in which he was looking at medium-chain fatty acids and monoglycerides as antimicrobial compounds.
Dr. Charlie Elrod (00:03:19):
And I thought it would be really interesting to bring to that natural bioactive conference, this perspective on bioactive lipids and how they might be you know, useful in, in deploying in, in livestock agriculture. Unfortunately for the conference, Josh was just even in that month leaving us and taking up a faculty position at sun young Quan university in Korea. So he wouldn't be able to join us for the conference, but we, we struck up a friendship and a collaboration he has since been a consultant of ours and has more recently joined our board of directors as an important scientific advisor. And, and so we've enjoyed a wide-ranging relationship over the last four years. I think it has been Josh and you know, we've had a lot of fun exploring a lot of different areas together.
Dr. Charlie Elrod (00:04:20):
Josh's background is largely in human fields. He's studied gastroenterology chemical engineering biophysics, all kinds of different fields. Josh holds a couple of patents for antiviral peptides, again against Ze and Dinga viruses. So, and has, has spun those off into, into commercial commercialization. So we're really lucky, to kind of drag him into agriculture and, and help him address some of the challenges facing livestock. And in particular, these viruses are pigs all around the world. And with that, I would turn it back over to Josh. If you wanna fill in any of the gaps, which I only covered the 30,000-foot view of
Dr. Josh Jackman (00:05:11):
Yeah. First of all, thanks to Scott and Charlie for, you know, inviting me to join you today. And, you know, one thing that's kind of funny, you know, a physical onsite meeting that got kind of, you know, I wasn't able to attend couple years ago, turned into four years of virtual collaboration now with COVID and everything. So, you know, it's been kind of an ironic twist, but, you know, we had a lot of great fun over the last couple years doing great science combining disciplines that normally people don't think about, you know, combining, you know things like chemical engineering and physics and different type of sensors with, you know, agriculture, livestock production, and, you know, it's been a kind of a creative fun journey. And I think it's just you know, really beginning there, there's so much more you know, ahead of us. But you know, a lot of great questions are, you know, coming up every day when we kind of find an answer to one question, 10 new questions emerge. So, you know, it's just kind of a journey and I, I think it's, you know, been quite fun to kind of, you know, go this way. So I'm really happy Charlie reached out to me. It was probably the least expected email I've gotten in a long time and opened a whole new world to me.
Scott Sorrell (00:06:18):
Well, Josh, we're looking forward to the conversation tonight. You bring, you're gonna bring quite a bit to the party. Tonight my co-host is Dr. Ken Sanderson. Ken is a veterinarian and I'm sure has a great interest in the on-farm application of these new technologies you guys have been researching Ken you've joined us here a couple of times before at the real science exchange. And so I look forward to your veterinary perspective to get us started here tonight. Charlie, can you tell us how you got started down the path at looking at lipid lop viruses?
Dr. Charlie Elrod (00:06:54):
Yeah, so it's, it's probably been five years ago or so that you know, we, we started as largely a ruminant focused company, but I knew we didn't want to keep all our eggs in that basket. And at the time, as I talked to some of my friends in the swine industry P E D had recently swept through North America and us pers was a, a consistent and, and annual problem for swine producers across the country, you know, costing, you know, over half a billion dollars in, in losses every year. And so I just wanted to, to kind of reach out and, and try and find some new technologies in a new species so that it, you know, broadened our, our product development pipeline, but also broadened our species interest just in a, in a matter of diversification.
Dr. Charlie Elrod (00:07:49):
So, I saw some anecdotal data out of Europe about the use of glycerol Monolo eight in combating pers infections or, rather in preventing pers infections. And so based on, you know, those few reports I started digging into the scientific literature and there was, you know, a pretty good body of evidence that these Mon glycerides and, and medium-chain fatty acids could be antimicrobial. And some evidence of there being antiviral against some specific viruses S stomatitis viruses is one that I came up with or, or rather was, you know, I found in the literature, but then where the most work had been done was actually to be found in the human aids-related research literature. So human immunodeficiency virus, research literature, and there were a couple of papers, several papers, one of which was in nature, which described how transmission of aids could be prevented with the application topical application of glycerol Monolo.
Dr. Charlie Elrod (00:09:10):
And so digging into that sum you know, I, I, I just came to understand that, you know this monoglyceride has several very interesting properties it's antimicrobial, as I've said, it was also antiviral against the HIV, and it was also anti-inflammatory. And so these authors in that nature paper hypothe that part of the way that GML could prevent aids transmission was upon exposure of epithelial tissue to the virus. It would typically raise an inflammatory response and that inflammatory response, in turn, you know, recruited macrophages to the side of the infection to help fight the infection as they're, as they're supposed to do in a, in a typical infection, though, those macrophages are the target for the virus. And once the virus enters those macro Fages, then it begins replicating. And those macrophages circulate throughout the body and spew virus as they go, excuse me.
Dr. Charlie Elrod (00:10:28):
So if the GML tamps down that initial inflammatory response, it precludes the recruitment of macrophages or certainly reduces the recruitment of macrophages. So they don't then become infected and go spread around the body at the same time, the GML is antiviral. So it's reducing the viral load there at the site of infection at the same time, it's leading to these anti-inflammatory reactivities. And so in essence, what they found, and this was done in a, a monkey model. So it was the Simeon immunodeficiency virus, not human but they found that it could practically eliminate the transmission of aids, but again, through a topical application of GML, you know, at the, of, of the infection or transmission. So
Dr. Charlie Elrod (00:11:44):
Most of the rest of it was you know, aids-related data, but kind of showing proof of concept that with a lipid envelope virus, maybe this could be effective against pers and you know, they listened respectfully and it, you know, actually the call went on for about two hours cuz there was great conversation around it, but we took it from there and just began kind of chipping away at the different pieces of that story to see if we could build the monoglyceride antiviral anti-inflammatory story until we had a pretty comprehensive portfolio, if you will, of data to support its use in this kind of application,
Scott Sorrell (00:12:26):
Just kind of a point of clarification. So being antivirals that against all viruses are only the lipid encapsulated or, or envelope viruses
Dr. Charlie Elrod (00:12:35):
Yeah. At, at this point and, and Josh, please chime in at this point we, we believe it to be primarily against the lipid envelope. Yeah. Viruses. So that would include P E D pers African swine fever some of the poultry viruses per, you know, coronavirus rotavirus, two that afflict calves you know, there could be applications there too.
Scott Sorrell (00:13:01):
Sorry. I was just gonna ask real quick. Is there a sense of what percent of the viruses economically important viruses are lipid envelope? It sounds like a lot of them
Dr. Charlie Elrod (00:13:15):
Josh published another review just a year ago, right?
Dr. Josh Jackman (00:13:20):
Yeah. That's actually what I was gonna bring up, Scott, your questions perfect. No, no, no, no. Perfect. sorry. Do you wanna go first? I
Dr. Charlie Elrod (00:13:25):
Mean, I was just gonna say that in this review, Josh points out that most of the great human pandemics of the last hundred years, I think you, you documented almost all of those were caused by lipid enveloped viruses. I'll let you elaborate Josh.
Dr. Josh Jackman (00:13:42):
Yeah, no, Scott, your question's a really good one. Cuz one thing, you know, this field of kind of targeting lipid envelope in the viruses we've been doing it for human applications, even myself from about 2008, two and 10 range. Researchers in general, maybe two, three decades, but always one question comes up, you know, oh what, well, you can stop some of the viruses, but there are non enveloped viruses too that don't have this envelope. What about them? For example and, and the thing is about a year, year and a half ago, we, we started thinking about, okay, there's nonenveloped viruses, there are these lipid envelope viruses, you know, how important are these two groups, no one really, you know, thought about it. So what we did is we looked at kind of what were the all the epidemics pandemics over the last 10 years how many have been caused by lipid enveloped viruses?
Dr. Josh Jackman (00:14:31):
How many have been caused by nonenveloped viruses, and what we saw is that about over 80% and all the big ones have been caused by lipid envelope viruses for human populations? And also even for animal populations all have been caused by lipid envelope viruses too. So we just saw that there's huge economic significance, huge significance in terms of what's affecting people. What's affecting livestock. With these lipid enveloped viruses, it's not to say non enveloped viruses are, are not important, but really when it comes to outbreaks pandemics epidemics nearly everything's been caused by lipid Vil, low viruses. So huge significance in this. And you know, this is really where, you know, meeting Charlie a couple of years ago, really right before COVID 19 or a year or two before, it was a fortuitous timing in terms of really taking this technology that's been developed for human populations for a long time. Combining it with, you know, Charlie's scientific curiosity and really kind of merging the human and livestock challenges of viruses and, you know, building a research program that can potentially address, you know, all these different types of the envelope, viruses, economic importance, as you mentioned.
Scott Sorrell (00:15:46):
Yeah. Can you guys kinda give us an overview of some of the research that you've done with the GML to date, and what are some of the key findings and maybe some of the applications that you might have discovered?
Dr. Charlie Elrod (00:16:01):
Yeah, so you know, as I said, we started with, a search more oriented towards pers because it was the most prevalent challenge facing swine producers at the time. We made a few stabs, at determining whether GML was antiviral. We didn't have the protocols down. Right. And so, but then ASF burst onto the scene. And, and by that time, Josh and I, I had been working together for six or eight months or so. And so, you know, Josh doing his due diligence came across this lab in Armenia that had been publishing on ASF for about a decade because they had had endemic ASFs circulating in their swine population for that length of time. This group was, it was an antiviral defense group, which is part of the Institute of molecular biology at the national academy of science in Armenia.
Dr. Charlie Elrod (00:17:08):
So the head of that antiviral defense group Hova came car we embasicallyim, set up a call, and established a collaboration. And so we've done, several studies with him, both with the medium-chain fatty acids and monoglycerides, but also then subsequently with some other classes of compounds. And so we kind of started at the time. There was a, a whole lot of you know, publicity and, and awareness of medium-chain, fatty acids as potential feed litigants. And so we, we started with that just a, you know, simple in vitro assays, looking at individual medium-chain fatty acids, and some of the monoglycerides to determine whether they were Vertical. And then if they also had additional effects, which would prevent viral rep application. And I, I try to distinguish those because they're kind of two different levels of activity.
Dr. Charlie Elrod (00:18:15):
So virus, I would be directly inactivating the virus. Whereas then what we call antiviral could include, you know, inactivation of the virus, or it could include some other D disruption of that, either viral entry, attachment, or entry unpacking replication rebundling and then exocytosis from the host cell. So any of those steps are prone to disruption, but we've kind of dumped them into, you know, the VI, a recital, and the antiviral as two different kinds of buckets, if you will. So we found that at I'll say fairly high concentrations, five millimolar all of the medium-chain, fatty acids, and GML that we tested had roughly similar virus modal. So direct inactivation of the virus activity. So 1.1 to 1.7 log reductions in the amount of infected ASF virus. Okay. When we tested lower concentrations of the fatty acid it's in GML.
Dr. Charlie Elrod (00:19:31):
So about 20 times lower concentration, we found that only GML had that virus IAL activity. So the medium-chain fatty acid did not, and, and GML did so. And then, you know, the work that Josh has done in terms of these and their interactions with membranes on, you know, in vitro supported lipid by layers is the system he uses that there are certain physical characteristics, which would,inessence, dictate why or why not these different compounds would have the effects that they do in Josh. You wanna elaborate on that? You know, why are the M CFAs here and, and GML there in terms of yeah.
Dr. Josh Jackman (00:20:19):
Efficacy? Yeah, no, it's a great question and point. So, you know, one thing with these biology assays, when you study ASF or a lot of these viruses, you know, they, they take time, they require a lot of safety requirements, a lot of really high technical expertise. And, and you mainly looking at the output, like, does it kill a virus? Does it not? But what we do in, in our research group, and one of the collaborations we do with Charlie too, is really from more of a kind of engineering, chemistry perspective, understanding, you know, why these compounds not work, not only do they kill a virus, but why do they kill a virus? You know, how can we compare, how do we judge, why M CFA or GML is better or worse for a certain application or comparatively, how do they work? So what we've done is developed more simplified experimental tools where we mimic a kind of viral membrane but using safe materials that we can use in any lab.
Dr. Josh Jackman (00:21:15):
You know, I, I'm in my, my parents' house in Florida visiting. Now I could experiment here, you know, for example, you know, it's quite safe. I don't need to be in some special laboratory, you know, in the middle of nowhere, you know, in a real I secure facility, no I can do anywhere. So it increases accessibility. But the really powerful thing is that we can look at the interactions themselves, not only if something happens the effect, but we can look at the cause so we can understand why a compound works, why one may be working at 10 times, lower dose than another compound. We can understand the basic principles using these kindel membranes. We call them kind of virus mimicking platforms, and we can rave a lot of different types of scientific measurement techniques that we can study these processes in a very detailed manner.
Dr. Josh Jackman (00:22:05):
For a long time, you know, people have done these kinds of in various contexts, usually fundamental kind of chemistry labs, but one thing cool about this ASF work is that we saw for the first time a connection between these laboratory results, what we call kind of biophysical chemistry studies in actually the the implications for antiviral activity and ASF. We saw a kind of a perfect correlation between how a compound would work in terms of antiviral activity against ASF versus the concentrations we predicted would work from the past 10 years of engineering research. So really it's been a helpful approach to kind of complement the biological studies and build, a better understanding of what's going on. Not only for fundamental understanding but also the application because we can understand, okay, if we take this compound, how will it probably work against ASF or pers or P E D V which one's the best to pick? How can we maybe take two compounds and make them work better together than one compound alone? So really gives us a lot of kind of chemical knowledge that we can use for practical purposes.
Dr. Charlie Elrod (00:23:16):
So the ability, I, I think maybe part of the reward for you has been that translational step that, yeah, definitely that takes it from, you know, you've been in the lab and, and doing all this great work and, and know as so many graduate students do at, at some point, they're gonna ask, what do I do with this
Dr. Josh Jackman (00:23:36):
What's exactly. I've been able to incentivize my students with meaning much better. So my students,
Dr. Ken Sanderson (00:23:46):
So, Charlie and Josh, you talked about camping down the inflammatory response. Mm-Hmm,
Dr. Charlie Elrod (00:24:26):
Yeah. And, and Ken, if I can't answer that completely it's because I haven't read that nature paper here in the last few weeks, to understand, but so, so in, in that nature paper, they used cultured human vaginal EPIT cells. And then they looked at inflammatory cytokine expression. I P three alpha and, and others and b they could in vitro reduce the level of those inflammatory cytokines in the face of n exposure this virus. Okay. I think then in this, in the monkey model of action and preventing transmission, they did do some tissue measurements of macrophage infiltration and, and you as a veterinarian would know better than I, how one might do that. But you know, they could, my recollection of it is that they, they could he recruitment of macrophages and infiltration and inflammation into that tissue into the vaginal tissue, where they were applying the treatments both the GML, as well as the virus exposure.
Dr. Charlie Elrod (00:25:50):
We wanted to follow that through and just in a sense update and validate it then a different system to see if we got a similar type of response. So we worked with Barry Bradford and one of his graduate students, Sarah Suski when Barry was at the case to eight and they had developed a mirroring cell model that measured the expression of NF CAPA beta, which is kind of a master signaling cytokine that kind of sits on top of the whole inflammatory chain in response to some stimulus in, this case, LPs exposure. And, and so what we were testing, not only glycerol Monolo but also straight laic acid and the Methodist of laic acid. And we saw a very nice dose-wise reduction in the expression of NF CAPA beta, you know, in response to LPs. So the lower acid or its analogs that were in the system, the lower, the expression of NF CAPA beta.
Dr. Charlie Elrod (00:27:02):
So that may be part of your question. I think the other part is how to do you kind of balance the, need for that macrophage recruitment and fighting the infection versus keeping 'em away. And I, I think it's, it's probably some kind of biological balance act that, that not totally within our control, certainly. So, you know, tamping it down some also reducing the viral load at the end of the day, if that results in fewer macrophages getting infected and fewer virus particles surviving in that mucosal environment, you know, whether it's nasal or old wherever then you've, you've improved. The chances of that host animal are kind of, kind of a mass balance type of
Dr. Ken Sanderson (00:27:54):
Yeah, it's a really interesting concept, I guess I'm kind of curious, were, were you able to line in some kind of quantitative manner, the macro FA activity or camping it down against the I'm gonna call it the hole punching technique within the viral membrane so that you had this endpoint that was a bow or is that, is that almost, and does that depend on which fatty acid you're using?
Dr. Charlie Elrod (00:28:33):
Yeah, so, we have not done the InVivo studies to, in a sense replicate that work from the nature paper with an SIV. That would be interesting. We have through, for instance, this Pipestone challenge with the pers virus, you know, the GML was fed at a level that allowed the treated pigs to maintain normal growth rates maintain normal you know, mortality morbidity but also not have any well, very few positive oral swabs, no zero conversion and, and no clinical signs of disease. So at that kind of a level and, admittedly crude kind of study in the grand scheme of things, it was effective. So I'm not sure that we'll ever need to get to kind of the, te, the pharmacological level of, okay, we want, we want a 10% reduction in macrophages and we want a 90% reduction in, in virus load. And, and then we, we've kind of tuned the perfect balance for maintaining health and, and, and responsiveness to other check challenges, because at the same time that, you know, there's that potential exposure to pers or P E D they're also affected with, you know, bacterial respiratory challenges and, and whatever else. So, you know, you don't want to completely tamp down the inflammatory or innate immune response,
Dr. Ken Sanderson (00:30:20):
Right? No, that's, that's a great answer. I, I was wondering about whether there was a spillover effect in inadvertent depression if you like against other things that the animals are going to be exposed to.
Dr. Charlie Elrod (00:30:36):
Yeah. You, I mean, like anything too much of anything can, can be a bad thing. Sure. So yeah, I think we certainly could GML has been used in Australia at higher levels and, and Josh, you may remember, I think it's when they get to the one to one and a half or 2% of the feed, they can reduce feed intake and, and their fi their, or four retard maturation in the finishing phase so that they can delay delivery to market say market timing isn't right. Or feed supplies isn't right. Or whatever. And they need to, to s some animals down GML, I believe the author was Closky a researcher in Australia do a lot of work on that in terms of kind of timing pigs and using GML as a, almost a to, to reduce feed intake and just slow 'em down. So it certainly has that capability.
Dr. Ken Sanderson (00:31:38):
I, I, one more question of Scott will let me, but the
Dr. Josh Jackman (00:32:14):
Oh, it makes a lot of sense. It's not a simplistic question. It's an excellent question. You know, this is a tie in a lot with researchers generally when they study active compounds to inhibit pathogens. A lot of people looked in in terms of bacterial pathogens in, in, in historically, and, and with bacterial pathogens, you can imagine one hole in the bacterial cell membrane would be enough to disrupt a lot of things going on bacterial. So is living it needs to have, you know, ion gradients concentration gradients across this membrane and so forth. So, theoretically, one hole in a bacteria can cause a lot of damage. When you go to viruses they're quite different. So actually at least in, in really aid research for other types of compounds, like antiviral peptides, which make holes in, in viral membranes what we've seen is one hole is not enough.
Dr. Josh Jackman (00:33:09):
So actually you need to make a critical density of holes in this virus membrane to C cause it to kind of collapse. So are a working model of this. And that was for peptides, but, we generalize it a bit just conceptually. But, but it, it seems that in general, more than one hole is necessary for a virus membrane to become inactive or in ken down. And, and we, we think that that structural damage is really important, not just poking a hole to damage like, or to affect concentration gradients and so forth, like with bacterial cells, but, but pretty significantly damaging it to now, break the structural integrity of the virus particle. So I'd say multiple holes. Now, the one flip side is that there, there is a there's caveat to this. That doesn't seem that it's necessary to break the virus particle to stop it from causing infection.
Dr. Josh Jackman (00:34:08):
So the thing is usually when virus particles infect a cell, what they do is they need to the cell, which means that the human cell or animal membrane and this virus particle membrane, they kind of fuse together. And then this is a kind of dynamic process where shapes are changing and things need to kind of merge together and we call this fusion. So actually sometimes before you start damaging the membrane and making it like Swiss cheese you can, some, we think that these compounds at little bit lower doses can already start preventing the viral membranes from fusing with cellular membranes so we can prevent infection. So there's some, depending on the exact compound depending on the exact environment conditions we think that you can have at least two kinds of modes of action that are kind of related, a little bit nuanced.
Dr. Josh Jackman (00:35:07):
One is kind of preventing the virus from actually fusing with cell membranes where, where maybe it doesn't make a whole per se, but it, it kind of, this compound might kind of wedge itself into this virus membrane, and it kind of change the properties of this virus membrane in and there's been a lot of research into these areas for various types of compounds that can co stop fusion. The more extreme case is when a compound cay kind of rupture or make a hole in this membrane and break it. So, it's an evolving landscape with a lot of mechanistic findings well with a lot of MIS mechanistic possibilities, but what we think that you know, your simplistic question is, is nothing but nothing simplistic at all. It's you know, as I said, an excellent question, it really comes to the kind of the heart of this kind of research in terms of the mechanism and, and, and what context do things work and, and how do we define the potency and so forth. But it's a great point.
Dr. Charlie Elrod (00:36:04):
And, and Josh, in, in terms of what we all know way too much about in terms of the membrane bound proteins. Yes. Whether, whether they're, you know, a spike protein that's used for receptor-mediated attachment and infusion with the host cell or whatever destabilizing that lipid envelope around those surface, or those membrane-bound proteins can destabilize the protein confirmation themselves and break down that, that process, or, you know, kind of set 'em low, or as we found in the work with ASF that P 72 capsid protein, we saw a very significant dose dose-dependent radiation of confirmation intact P 72 protein. So yeah, I think, it can have a lot of different means, of disrupting those critical early steps and viral infections.
Dr. Josh Jackman (00:37:06):
Yeah. Megan, add one thing to that, Terry it's thanks for reminding me about, the protein effects. So these virus membranes, you know, we talk about them lipid envelope. That means lipid molecules are one type of kind of fat molecule in the virus particle membrane, but also they still have very important proteins in this membrane too. And the proteins in the virus membrane depend on the lipids being happy. So if you kind of make holes or you start damaging these lipids in the envelope, also the proteins can kind of stop working. So well, so we maybe can tweak the structure of the protein by interfering with these lipids. And these proteins are important, cause in some cases they're necessary to bind to the cells to infect them, for example. So there's a lot of downstream effects, but, you know, I guess even though the research sometimes sounds fancy and essentially it's how many different ways can we break a, you know, break lipid membrane, essentially, how many, how can we break stuff essentially, how many different ways can we do it?
Dr. Josh Jackman (00:38:03):
That's kind of the gist of it. But what we see is there's, there are other accessible ways, you know, as I said, you can kind of interfere with fusion. You can make holes in it. As Charlie mentioned, there's kind of maybe downstream effects. If you affect the lipid envelope, you also affect the related proteins. So this is kind of multi-face. You know, what seems simple in terms of just breaking the virus in one sense becomes, you know, quite more nuanced and complex very quickly. But that's why we also see many interesting opportunities to also utilize it in various application contexts in, in more selective manners based on this nuanced understanding of what's going on and you know, how we can utilize this for applications.
Dr. Charlie Elrod (00:38:45):
So for, well, two points to follow on that. One is a lot of these membrane disruptions happen in seconds. So Josh some great video in, in this artificial membrane, the supported lipid by layer membrane, where you add the monoglyceride or, or fatty acid or whatever. And within milliseconds, you're seeing these membranes just blow up, you'll see e tubular formation, you'll see bud formation. And then, and then they just blow apart. So really dramatic video of what happens literally within seconds. So very fast-acting. The second point, oh, is that you know, knowing this about this class of compounds, and then I'll just turn it quickly to the work we recently published on flavonoids we screened a library of close to a hundred different flavonoids, which we believed could have the potential for anti-ASF activity or antiviral activity. And we found a number that was had antiviral activity against ASF.
Dr. Charlie Elrod (00:39:59):
We found five with the significant activity that we explored a little deeper and then one which we, you know, chose to pursue more deeply. And it had no virus IAL or very little virus IAL act, but it did through various studies to look at the timing of entry and the timing of exit and, and various other means found that it wide the host cell and inhibited viral unpacking in the very earliest stages of viral replication in the host cell. So coupling some technologies that say had a high degree of virally activity with some other inhibition of say, viral unpacking, and replication, you know, could lead to some very robust types of antiviral. You know, mitigations,
Scott Sorrell (00:41:06):
Go ahead, Scott. Well, I was just gonna kind of drill down into how much do we know about dose rate and, where, where is the site of activity? Is, is it the plasma? Is it in the cytoplasm? And then how much do we know about, you know, what levels of TIS we need to maintain a follow-up question to that might be, you know, I'm, I'm assuming these or medium-chain fatty acids are being metabolized. And so how long what's the duration we have to maintain some of these TIS, there's just kind of a whole lot of questions in there. I know Charlie's laughing, but
Dr. Charlie Elrod (00:41:41):
Scott Sorrell (00:41:46):
Three hours. We'd be, we shut her down
Dr. Josh Jackman (00:41:48):
After three, you were not joking
Dr. Charlie Elrod (00:41:52):
Wow. So much there, Scott. You know, we, we did some of the dose titrations, at least in vitro and we, we haven't done this. We haven't done any InVivo studies with ASF and pigs where we have some underway with P E D and pers in pigs in which we hope to get at, at some of those dose titration kind of questions how much you need, you know, Josh has a friend that is a, a Russian mathematician who has modeled viral load and subsequent you know, expression of disease. And you know, we've talked about bringing him in any kind of modeling, okay. If we get this much reduction in viral load, what's the implication for that, or if we get this much or, you know, and, and what's the timing of that and frequency of exposure, just all kinds of questions around this, which, you know, Josh could maybe take me under his wing and I'll do a second Ph.D. or something, but
Dr. Josh Jackman (00:42:59):
More than welcome, anytime you'd be the best Ph.D. student
Dr. Charlie Elrod (00:43:05):
So boy, there's a lifetime of work in that, in that question, Scott, great
Dr. Josh Jackman (00:43:09):
Question. So maybe I can add a little bit to that as you know, Scott, you asked many excellent questions, and the simple answer is, you know, T BD you know, TB determined all of this. But I would say, you know, so far, you know, we, we have a very good understanding of kind of dose levels in terms of in vitro, meaning that we can understand what type of motor concentrations we need to see activity. And that's very correlated with between the engineering and the virology work. And, and also we can understand that in terms of even feed mitigation, for example, now I think the next frontier is taking things, you know, into the animal and, and understanding this in terms of more the pharmacology the, the input dose versus what is available amount of, let's say, GML in, in, in animal blood, let's say, or in, in various organs and, and so forth.
Dr. Josh Jackman (00:44:05):
I'm understanding that the pharmacology of that a bit more this is a new frontier for this kind of what we call antimicrobial lipids, whether it's CFA, which you might hear about sometimes the medium-chain fatty acids, whether it's GML. There's been a wealth of studies done in vitro in, in, you know, laboratory test tubes a lot of great work and, and feed mitigation over the past few years. But that's the next frontier to take it in animals to correlate the dosing with what we see in the animal. Even, you know retrospectively, you know, there's a lot to potentially learn from GML has been used as a dietary supplement or food supplement for, for, in humans for a long time. There there's can be some learn from the dosing from that kind of cases in terms of what's a recommended dose and, and so forth.
Dr. Josh Jackman (00:44:55):
But even where there's for human applications, livestock applications the, the pharmacology side of this is huge potential and, and just, it hasn't been achieved yet. I mean, it's really where the next level of studies needs to go. You know, as Charlie mentioned, we have one collaboration at Cornell University for doing some of this work with, with some viruses in terms of looking at really dose-response in a pig model and so forth. So I, I think, you know, a lot of this work will begin to become unraveled but, but, you know, huge potential cause cuz right now we've seen certain initial applications in terms of like feed mitigation and so forth where it's pretty validated that it can work. But really in what context can this be used preventatively therapeutically in animals is, I think the next level of this, Charlie, is there anything you wanna add to that?
Dr. Charlie Elrod (00:45:50):
Yeah. Thehenhe another part of Scott's question about metabolism and you know, so, so what we know now and what is out there in the literature now is that by feeding this monoglyceride, so, you know, it's one fatty acid hooked onto a glycerol molecule where it's hooked on matters. So if it's hooked on to the number two or the middle carbon of the glycerol backbone, it basically will be absorbed transported to the liver and a terrified into triglyceride. But what they've found is that if it's at the one or three carbon, if the fatty acid is attached at the one or three carbon, then it will bypass transport for whatever reason to the liver and will circulate in, in, you know, systemic circulation in the lymph and in the blood and, and whatnot. So, and it's a stereoisomer. So whether it's hooked to one of the three doesn't matter, it's the same either the way you flip it.
Dr. Charlie Elrod (00:47:01):
And so, you know, we, we did a, a crude proof of concept study in SALs to see if we could pick up GML in milk. So we fed the SALs, just, a whacking huge dose equivalent to something like 20 pounds per ton of feed, just brute force. Could we get into the milk? We did see about a sevenfold increase in the amount of GML in milk over the baseline. We went back to a, a more like maintenance level, two kilos per ton, four and a half pounds per ton of feed. And we saw about a fourfold increase in GML over baseline. So it does get into the milk it gets into circulation. Could this confer some benefits to the piglet? We think so there's some data out of the University of Iowa. Peter sliver, I believe his name is who's done a lot of studies on human breast milk and found that human breast milk has about 400 times more GML than cow or SALs milk. And he believes they believe that this confers some benefit to the babies in terms of antimicrobial, antiviral, and anti-inflammatory activity. So, you know, if we can translate some of that into livestock production practices and, and mitigate risks to these very most susceptible neonatal animals then, you know, that's a good
Scott Sorrell (00:48:42):
Thing kind of building on that. Josh had mentioned that you know, GMLs being used currently and, and human nutrition, I guess you can probably go get it at GNC. So what, what's the indication? Why are people taking it?
Dr. Josh Jackman (00:48:55):
Go ahead, Josh. Oh, okay. Then you know, that's, it's a great question. You know, the general thing, if you look at the product labels, you go to G if you go drive over to GNC, you look for it. What UFC is generally they say general immune support function. What does it mean?
Dr. Josh Jackman (00:49:45):
I, I think that there there's a lot to be done. But you know, anecdotally what, what we know is from, from a human perspective it's, it's safe to take in terms of the supplement it's been used for several decades. So it's safe from, from the animal studies, the haves been some studies from Australia that Charlie mentioned earlier, where G has been used in, in feed studies looking at growth performance so forth and had some positive effects. Also had some antibacterial effects if I remember correctly in terms of reducing some disease-causing pathogens, the exact name of the pathogen escapes me, even I study virology, I can forget the name very easily
Dr. Charlie Elrod (00:50:35):
Microbiome, like
Dr. Josh Jackman (00:50:36):
An away from yeah. Shifts in
Dr. Charlie Elrod (00:50:37):
Species and, and that kind of thing, and
Dr. Josh Jackman (00:50:40):
Exactly, and a broad scale and, and reduced pathogen levels kind of increases in healthy bacteria at this same time. So, there are positives there, but really, you know, still teasing out the molecular mechanisms and so forth, I think is the next frontier of this kind of research. And, you know, Charlie kind of filled in the one study that I had forgotten about the kind of bioavailability that he had mentioned for some of these animal studies, but, you know, as Charlie saw there, there is, there can be very high levels of GML that, that, you know, enter the, you know, animal milk and so forth that, that have been seen with some of these studies he's done. So I think there's, you know, potential there. And, and even in terms of metabolism, if you think about, well, what happens if GML becomes metabolized, for example, breaks down, you know, what is the breakdown product?
Dr. Josh Jackman (00:51:27):
How quickly does this occur in the body? Even one of the main metabolic products of GML is also antimicrobial. It's called Loic acid. If you break it down, it breaks down into the fatty acid we've ever seen in, in our lab in terms of biophysical, these chemistry findings, that if you have a mixture of LA and GML it can work better than in GML by itself. So even when you think about this, some kind of metabolic perspective, if GML goes into the body breaks down, let's say 50% degradation, let's say, and then that, that ends up being like a 50% GML, 50% LA mixture. This might be even better. So, you know, I think it's, it's an exciting area where we just need to keep doing studies and, you know just, you know, takes investment, I guess it's, you know, the one, one thing that, you know, animal studies are a big undertaking. But you know, as long as the momentum's there I see huge, you know, potential ahead.
Scott Sorrell (00:52:22):
Hmm. So my next question kind of falling up to that is one, we kind of touched on a little bit during the webinar, which is, you know, COVID team. We know that that is, a lipid envelope virus. We've all become many virologists during this whole
Dr. Charlie Elrod (00:53:04):
I'll neither confirm nor deny
Scott Sorrell (00:53:09):
Well, maybe a better question is, do you know if anybody he's looking into that, it would seem natural that they might,
Dr. Charlie Elrod (00:53:18):
I, I don't know of any structured research programs that are they're I would hope so. I will say that when I started running a fever last Thursday night and then got home on Friday, the first thing I did was took a good dose of GML.
Dr. Charlie Elrod (00:54:34):
And they identified about 26, which could be possible markers, but when they narrowed it down, the two that most differentiated the healthy from the infected people were the presence of GML and monomer state. So the C 14 fatty acids are hooked to, a glycerol molecule. So the mono glycerol of mono of Mesick acid. So those two monoglycerides were the ones that best distinguished healthy from infected patients. And those two could be picked up in much higher concentrations in the healthy patients than in the infected patients. So those authors hypothesize that it might be that the GM and Monte state had, some sort of protective effect and might in the future be used as you know, as a preventative against COVID. And, and the only reason we knew that that paper got published, they ended, they cited our work from the African swine fever virus work, as, you know, evidence of, you know, GMLs antiviral activity. So it, you know, we just got an alert through the system that our paper had been cited, and I went to look at it and came up with this stuff. So it's, I, I think it's could be a promising area, you know, for this and other future viral pandemics, epidemics.
Scott Sorrell (00:56:16):
Yeah. So is the assumption then that the healthy people had higher levels to begin with and therefore did not become sick, or perhaps the people that got sick they're somehow they're depleting their levels.
Dr. Charlie Elrod (00:56:28):
Yeah. And, and they couldn't tease that out from the data. They kind of hypothesized that the healthy people, even though some of them had had previously had COVID at the time of sampling, at least had higher levels of GML in their breath. To me, kind of the significance of that is that the GML was circulating in their mucosa in the respiratory tract and was there ready to be expelled in their breath. So to me, that, that, that gives CRE credence to the idea that perhaps feeding this will allow for its circulation wherever to whatever mucosal tissue might, you know, be the target of a virus, you know, exposure and then help in that whole, you know, inflammatory antiviral kind of
Scott Sorrell (00:57:25):
Mm-Hmm
Dr. Josh Jackman (00:57:27):
So I think one thing to add too, is, you know, you want product marketing claim, you know, of course, you need to be careful to say, you know, that it's working against COVID 19. I'm sure every supplement company that listened to this would love me to say that. But you know, there's a lot of studies that substantiate that, but, you know, based on Charlie's, you know, seen in terms of what he mentioned in terms of what's going on in terms of the scientific literature and these associations between higher GML levels and, and reduced disease severity and, and so forth, I think there's huge potential there, but you can also think that this type of technology whether it extends to kind of human applications or, and animal applications, it has huge potential because it's also targeted lipid envelope viruses broadly. So we don't know exactly which virus will cause the next outbreak. And then we don't know which population be affected. We don't know exactly which virus, but we'll have something that is potentially kind of a first-line countermeasure that could be used for stopping the next pandemic as well. So I, I think that's one of the huge values for this is not only stopping what exists now but also kind of preparing for the future mm-hmm
Dr. Charlie Elrod (00:58:35):
Dr. Josh Jackman (00:59:41):
Yeah. Then this is really one other unique aspect of this is it kind of runs counter to the kind of the traditional notion of how we develop antiviral compounds. Usually, we call it kind of one bug, one drug, or one drug, one bug we're kind of focused on developing an antiviral for specifically one virus, but this kind of, we can span the end of thinking to kind of one drug or many viruses and the human sensor, one compound many viruses in more of a broader sense. But having, you know, one CLA molecule class molecule that can work broadly against many important viruses is a kind of new thinking, a new paradigm in antiviral science in general, whether it's for animal populations, the human population. But, it has huge potential because it's not only addressing things now, which is, is how the one drug, one bug kind of concept works, but having compounds, having antiviral strategies that are potentially applicable to few sure. Challenges and having them ready from the get-go.
Dr. Ken Sanderson (01:00:47):
So that's intriguing at one point you talked about this disruption of fusion and, and that to me would seem sort of putting on a very old hat related to resistance development might have precipitated the idea that you could see some resistance develop because you haven't it's not ay activity you've changed the adhesion characteristics, but the virus is still surviving as it were it just, so does that change the opportunity for resistance
Dr. Josh Jackman (01:01:30):
Development? Yeah, that's a great point. So, we just put out a review paper and had a reviewer ask a similar question. Exactly. so it's a really good point. A lot of that early kinds of fusion inhibitors, these kinds of therapeutic drugs, and the human space, that's the virus fusion. They were typically kind of peptides that bind to the viral proteins on the surface to prevent them from making certain changes that are necessary for fusion. When you bind to the viral when your, your target is a viral protein resistance can develop relatively easy compared to targeting viral lipids because these proteins are encoded in the viral genome, how they're produced and, and it's more mutation prone, but by kind of evolution, the viral genome when it's reproduced it's it, the errors can be introduced more easily. And this allows the virus to kind of escape new drugs being developed to stop it in some sense with viral proteins.
Dr. Josh Jackman (01:02:28):
, this can be a big issue, especially, for certain classes of classical peptides targeting them. Now, recent more recently though, there are other types of fusion inhibitors, small molecules, and also things called Lippi peptides that associate with the membrane. These compounds they're either target the lipid envelope, or they are so potent because they associate with the lipid envelope to bind to the viral protein. So potently that VI resistance is, not such an issue with the latest classes of fusion inhibitors. So especially the main reason is cuz the lipid envelope really cannot evolve resistance so easily cuz the lipids in this envelope they're, they're not in the viral genome. So it's, it's a bit actually kind of maybe not so obvious that first glance, but the viral lipids are from the whole-cell membranes they're derived.
Dr. Josh Jackman (01:03:22):
Yeah. So they're not encoded in the viral genome. So, the virus can't mutate to kind of stop it. So, this is an issue that has, you know, really many people have asked this kind of question, you know, fusion inhibitors or resistance development. You put it very nicely and it is been a big problem, but for the latest generation, it appears less of a problem. And, and we've gone through the literature recently, and it appears that fusion inhibitors are targeting this membrane to date. And to my knowledge, there's been no clear evidence of resistance developing. Part of that, you know is just based on the, there haven't been so many long-term studies to do this, but even in the cases where they have kind of massaged the virus in presence of the drug, for many cycles, you don't see resistance development. We need to keep testing that over longer periods. Once things start reaching clinical trials or, and so forth, really seeing it in larger populations to validate that. But based on all the evidence to date, which is growing and accumulating it looks very promising that resistance development at least has a very high barrier if it's possible at all. And I think that's one of the big potentials for the future. I think a great point. You mentioned Charlie, did you wanna add anything to that?
Dr. Charlie Elrod (01:04:37):
Oh, I, I was just gonna say for maybe broad understanding that as a virus particle replicates inside the host cell, then buds of that DNA or RNA will repackage and reassemble and they exit the cell through the membrane exit the host cell through the membrane taking bits of that membrane with it. And that's what it's enveloped in is the host sells membrane. So that's why you know, it's, it's very generic. It's not encoded, in the viral genome. So, you know, very generic it's whatever host cell it came out of. That's kind of the constituents of its membrane. So again, very, very generic and, as Josh said, I think makes it easier to target.
Dr. Ken Sanderson (01:05:32):
So, having said that, what is protective of the host cell membrane from the activity of this fatty acid or the Monolo? So does that question make sense?
Dr. Charlie Elrod (01:05:51):
Yeah. Yeah. I had that question. I, I did a grad student symposium or seminar rather yeah. Up at Cornell a month or two ago. And a student asked that, well, you know, if this stuff just disrupts membranes, what about if you consume some and is it gonna just start, you know, opening up all the cells of your, you know, your gut lining and disrupting all those membranes and may have a better biophysical explanation for why it doesn't, it could just be a dose-response. I, I honestly don't know. You know, as I, as I did point out, it has been through grass certification. There's the whole dossier on the safety studies done as part of that grass certification with the FDA. We have that portfolio of documents. We haven't
Dr. Josh Jackman (01:06:48):
I can maybe add one more thing too. It's a, you know, another question because people are wondering, you know, okay, as you mentioned, you know, how can it target the pathogen membranes, not human membranes or what is this balance and so forth? One, you know, as Charlie mentioned, you know, it kind of depends on, on the context of, you know, the dose and so forth, but also me biochemical mechanisms of viral part membranes of virus particles versus human cell membranes are quite different. And one key aspect, which is kind of repair or mechanisms, virus membrane, if it's damaged, there's no way to kind of repair the membrane in human cells. There there's a wide range of biochemical mechanisms machinery that can repair the membrane, even if it's slightly damaged, let's say. So actually what researchers have seen is that some of these membrane-active compounds, study the mechanism very deeply in terms of some of the small molecule antivirals, not, not so much for, for GML and so forth, but some small molecules.
Dr. Josh Jackman (01:07:48):
They've seen how actually virus membranes can be damaged, but not repaired because the virus essentially is just a parasite. It's not a living cell. It has a very primitive structure in some sense. But cells mammalian cells, they're, they're quite sophisticated and, and they always, you know, encounter some type of damage is just normal operation. But they, they have quite stress or whatever. Yeah, exactly. I mean, a native of, and various types of, you know, damage to, to their, their structures. But they've evolved quite sophisticated machinery, to also repair membranes lipid synthesis, lipid maintenance, and so forth. So there's also a lot of discussion about these mechanisms to also better understand how these compounds can be used effectively against saying viral membranes, lip
Dr. Ken Sanderson (01:08:54):
All right, Ken, what he, he said, yeah,
Dr. Josh Jackman (01:08:58):
Very, it's still, it's still quite empirical too. Even with that kind of fancy talking, you know, as Charlie said, too, you know, there's still empirically, we see kind of concentration differences in terms of potency and so forth. So, you know, I can talk for, you know, three hours as, as Scott's hoping, you know, for all the detailed mechanisms, but at the same time empirically, we see this. And we just keep trying to understand the mechanisms behind it, but from an empirical perspective, it also looks very promising
Dr. Ken Sanderson (01:09:22):
Curious about the lipid nanoparticle aspect of the delivery mechanism for mRNA, how that connects into
Dr. Josh Jackman (01:09:33):
This. So, so, you know, really a great question that we, of the, you know, lipid nanoparticle technology in terms of just fatty acids, monoglycerides incorporating them can be important. You know, a lot of the delivery aspects that you mentioned earlier, you know, one of the needs for future research. So we've been discussing that a lot in terms of how nanoparticles can be useful for delivering, these compounds in terms of making them more biologically active, even after they're kind of diluted in physiological medium. So, you know, once you kind of administer fatty acid or monoglyceride to an animal, the concentration inherently becomes diluted as it enters the body. But how can we maintain high activity even upon dilution? So I think this is another huge area, for research in terms of nanoparticle technology and so forth.
Dr. Josh Jackman (01:10:20):
And, you know, as you mentioned, you know, the vaccine delivery, mRNA delivery, and all these things, it's kind of the first example highlighting how much potential this kind of lipid nanoparticles have. You know, it's one of, it's probably of the first example that validates it in the public eye of why we need to do this type of research. It, it builds on maybe 20, 30, 40 years of research in terms of lipid nanoparticles in general, but, and they were used for cancer studies and so forth, but really on a broad impact and, and, and, you know, COVID 19 vaccine delivery and so forth was the first example. But in terms of agricultural potential and so forth you know, Charlie and I discussed, you know, there there's huge potential for this kind of areas in terms of delivery and so forth. So I think that also falls within the kind of the next frontier of what is possible
Dr. Ken Sanderson (01:11:08):
The actual nanoparticle technology is got, I would've thought and sounded like a, you know, it does some crossover to some of this discussion and how else can we look at it in ways of delivering active molecules that we're interested in and what should we be thinking about? So that was part of something that, you know, as I read about the construct of the COVID vaccine, I, I was struck by the fact that until the lipid nanoparticle was incorporated into that, we had no way of putting the mRNA information in, into the host cell. So that, that was intriguing a, I guess one other part of this was to, you know, and I'm back to the I'm gonna call it the nondiscretionary disruption of the lipid membrane. So I don't know if that's the right way to say it or not, but, but, you know, we're in the calling business and, and phosphate colon being such a key component of lipid membrane construction. And, and so it's kind of interesting, you know, do you wanna be looking at things that actually help the host membrane preservation while letting the virus be a, or would you still, or would that just have this sort of generic ability to support the membrane cuz the virus can't reconstruct your point, right? Yeah. So it hasn't got the tools to do that, but our wholesales do so do we want to adjunct that repair if it, that makes sense what I'm saying? Yeah. At the same time
Dr. Charlie Elrod (01:12:57):
With something like Coline as a yeah, yeah. Donor for phospho Coline
Dr. Josh Jackman (01:13:04):
Yeah. I mean, I think the more we think about these questions from not only the effect, but you know, as you're starting to get into kind of what are the mechanisms, how can we use, you know, nanoparticle technology or these type of compounds to kind of do it the more we think about these things from kind of a physical perspective, you know, really kind of what's happening tangibly. I think there's a huge number of applications like that that can begin to emerge and really into the COVID 19, you know, vaccine kind of example you mentioned, I think it's a kind of serves as a really important foundation to motivate further studies for, for seeing lipids in a new light. So seeing the potential of lipid technologies and in many applications that maybe five years ago would've been less interesting, but you know, really seeing there, there is the potential there, we need to keep asking these questions, you know, we need to keep doing the kind of molecular-level understanding, as you know, Charlie and I have been doing it and some applications but we can, you know, keep growing that and, and see, you know, many new opportunities.
Scott Sorrell (01:14:08):
Yeah. So, sorry, Ken speaking, the three hours we're well, over one, which means a couple of things could mean we've got two hours to go
Dr. Charlie Elrod (01:14:37):
You know, I, I guess I would, I would say that just, you know, we started with kind of this there was some direction to it and exploring these medium-chain fatty acids and monoglycerides we've moved on to, to the fly adenoids and found some promising things there, you know, we've, we've just commissioned another series of work with a different class of compounds. So, you know, continuing to explore and, and bring in those different sources of, of whether it's this kind of generic mechanisms or more specific mechanisms as we found with the flavonoid was you know, there, there are lots of more discoveries out there and, and we hope to keep bringing some of those in doing what we can to, to understand them, publish that data you know, as, as openly as can and then, and then, you know, hopefully, bring new solutions to the livestock market. So this is, this is just a first chapter for us. Yeah.
Scott Sorrell (01:15:44):
Nice wrap-up Charlie. And with that, we'll flicker the lights and call the last call. And what I'd like to ask each of you guys is to give me you know, two key takeaways that our audience can take back to their, their facilities, their customers, and, and perhaps consider or start implementing. And Ken, why don't I start with you?
Dr. Ken Sanderson (01:16:11):
You know, I, I'm not sure I have key takeaways, but a couple of things that come to mind as you ask the question, the first one probably is, man, there's still a lot to learn, and I'm a bit, I'm more than a bit intrigued about, you know, cuz this idea of using these fatty acid has been around a long time, but the tools I guest understanding more about what we're seeing and why, why they're having some impact have been rapidly evolving. And so there are things, you know, that circulate from this conversation around whether or not we, we didn't talk about the
Dr. Ken Sanderson (01:17:37):
So it's a fine line, lots of discovery, lots of neat things. And, and yet I, I'm curious how we learn more and yet continue to have access to the tools as we go. Mm-Hmm
Scott Sorrell (01:17:53):
Josh appreciates your participation today. You brought a lot of very interesting information. What kind of takeaways do you have for our audience?
Dr. Josh Jackman (01:18:01):
Yeah. You know, first of all, you know, thank you for, you know, including me today. And you know, I think, you know, one of the main takeaways that I would see in this is to think about GML and, and fatty acids. Monoglycerides this kind of new classic compounds are evolving, emerging classic compounds. You know, they've been well studied for a long time but really to view them in a new light in terms of what we understand from the mechanisms have the potential to solve some of the major viruses, bacterial challenges of our time, and potential of the future. And so while kind of, you know, considering that kind of regulatory positions as was just mentioned, but viewing them as, you know, having huge potential for the future to stop the future virus and, and bacterial challenges. You know, we don't know what issue will come up, you know, one year from now, five years from now.
Dr. Josh Jackman (01:18:54):
But if it's a bacteria or viral pathogen, there's a good chance that it's a lipid envelope one. And you know, this is, you know, an emerging tool that we can use to potentially stop them. I would say is number one number two take-home point is this type of it, it cannot come from my lab alone. You know, it cannot come from an animal science facility alone. It cannot come from a virology lab alone. This is kind of shows the power of doing work and the feed additive nutrition research, agricultural research, more broadly speaking by really creating multidisciplinary teams of, of researchers from around the world best fits this, fits the need. But shows the power of collaboration across traditional disciplines to bring new insight to problems potential solutions, and drive innovation forward.
Scott Sorrell (01:19:46):
Yeah. Thank you, Josh and Charlie, for two things. And then also, can you tell the audience where they can find you and natural biologics?
Dr. Charlie Elrod (01:19:54):
Yeah. so I would, I would echo Josh's last point. I mean the cross-fertilization of ideas between saying Hoki, the virologist, Jeff, the Jeff
Scott Sorrell (01:21:12):
And where can they find you?
Dr. Charlie Elrod (01:21:14):
They can find me at our website would be the easiest place. So that's natural biologics.com and there are contact sheets and links to all of us and links to our research bulletins, which are freely available. All of the work that, that we've published we've made the, you know, we've made the decision and paid the fees so that it's all open access, so anybody can access at any time. So again, it's, we, we try to make us, our science an open book so that others can participate and learn from it and, hopefully, help push the industry forward. All
Scott Sorrell (01:21:54):
Right, well, thank you, Josh, Charlie, Ken, this has been immensely entertaining and interesting, and there's no doubt in my mind, we could have gone a full three hours. And with that, you guys have a standing invitation to the exchange. So anytime you want to come back, you've got some new information we're here for you. Even if you don't have new information, Charlie, Josh, you guys can come on back. So I, I, I thank you for the great information today. I also wanna thank our loyal listeners for stopping by once again, here at the exchange to get to know our guests a little bit better, and hopefully, you can take so home that will help you impact your business as a reminder, our real science exchange or our real science lecture series continues with monthly topics for both the ruminant and monogastric audiences and quarterly topics for companion animal audiences to register, visit val.com/real science. If you like what you heard, please remember to hit the five-star rating on your way out. Don't forget to request your real science exchange. The T-Shirt you just need the like, or subscribe to the real science exchange and send us a screenshot along with your address and size two an h.marketing at bache.com. I hope to see you next time here at the real science exchange, where it's always a happy hour and you're always among friends.