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Many drugs go after the unique viral enzymes but do any target their lipids? Viral membranes are of course similar to the host membrane but might have a different composition and do have a different curvature and protein composition. Is anybody aware of research or even existing drugs that attempt to hit the lipid envelope of viruses to limit them?

There are evolved molecules that target the lipid membrane, for example. A subgroup of those pore-forming toxins are cholesterol-dependent, so they might target a membrane high in cholesterol over one low in it. I'm trying to think out of the box here whether properties of the viral lipid membrane could be exploited in a similar way.

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  • $\begingroup$ For sarscov2 it would be more about S than E and M proteins. Otherwise there are molecular patterns in the lipid membranes that can serve to distinguish between self and invaders (this is more about bacteria than viruses for which double stranded RNA is a more common recognition target) but the exact recognition process is not understood enough to produce some drugs. $\endgroup$ – reuns Apr 23 at 7:55
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    $\begingroup$ Soapification is the process by which detergents break down the lipid envelope. Are you asking about soapification specific to viruses, or are you thinking more along small molecule targetting of lipis? $\endgroup$ – James Apr 23 at 14:31
  • $\begingroup$ Thanks, James. Most detergents would dissolve the virus and host cell membrane equally, don't they. If only we could make them more specific to the virus to also use inside the body? $\endgroup$ – SeanJ Apr 23 at 14:35
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The lipids in the viral envelope come from chunks of the host cell membrane. Therefore, something targeting those lipids is unlikely to be virus-specific, and not suitable for use in a living animal.

Out in the environment where the virus is found in surfaces and such, sure, one can target the lipid envelope using soaps/detergents and such, but you wouldn't want to take those internally.

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  • $\begingroup$ Thanks Bryan for weighing in. You think there's no way to make those prefer the viral membrane over host membrane using the lipid composition if different, the higher curvature or the unique membrane protein mix? $\endgroup$ – SeanJ Apr 23 at 14:39
  • $\begingroup$ @SeanJ It's not really a different lipid composition, it's ripped right from the host - even if there were measurable differences it's not really plausible biologically to sit and count them to start getting suspicious from a slightly different ratio. If you're targeting membrane proteins you're not after the lipids anymore :) - MaxB's answer covers this but you said in a comment there you were thinking of the lipids themselves, so I added this answer. $\endgroup$ – Bryan Krause Apr 23 at 14:59
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If you are talking about the proteins in the envelope, then yes: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6259279/

But if you are talking about the actual lipids, I don't think it's feasible: First, a drug molecule has to bind a lipid while not binding the host's lipids (seems unlikely, since they don't have well-defined pockets) Second, even if you could find a drug molecule that binds a lipid molecule strongly, there are just way more lipid molecules than protein molecules, so you'd need a lot more drug molecules than usual (protein-targeting drugs)

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  • $\begingroup$ I was thinking about the lipids themselves. Proteins are of course the usual target. It just struck me that I hadn't thought about whether targeting the lipid membrane is a possibility. $\endgroup$ – SeanJ Apr 23 at 14:19
  • $\begingroup$ If there was a molecule that could selectively bind the virus lipid membrane and punch a hole in it like in human complement defense or like the bacteriocin nisin, you would need only one of those. $\endgroup$ – SeanJ Apr 23 at 14:34
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Short answer: no in vivo drugs; yes for disinfectants. Most detergents and solvents would deactivate the virus at least partly by means of breaking up (emulsifying) the lipid membrane (as well as possibly by denaturing proteins).

Targetting the membrane is hard in vivo since it comes from the host cells; most possible drugs (eg snake venom phospholipases) would affect both equally. However, the host cell membrane has a strongly assymetric composition ("leaflet asymmetry") due to the action of enzymes that maintain it (flippases), otherwise the inside vs outside lipids would tend to equilibrate over time. This is used a recognition signal, and there may be some natural compounds that recognize specifically inside-out membranes eg lysenin. It is likely that the viral membrane is equilibrated, and so may be targetted by compounds like lysenin (although I haven't been able to find any experiments or published results along those lines).

I haven't been able to find much detailed info on the virus lipid membrane, so I asked a somewhat related question here before I found yours: What is the lipid membrane of SARS-CoV-2 made of?

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