From Sharks to Soybeans-- Squalamine as an antiviral

File this under "Maybe Nifty, Maybe Nothing"--

A couple decades ago, scientists found a compound in the liver of sharks that turned out to be anti-cancer and anti-microbial-- squalamine. Though its not the most popular component of the 'SHARKS DONT GET CANCER!!!!' myth you might have heard of, it is a part of it. Just Google 'shark liver oil' to see the wooers eat it up (literally).

Pharmaceutical grade squalamine (artificially synthesized in a lab from soybeans, not squeezed out of a thousand shark livers) might, at some point, be a useful antiviral:

Squalamine as a broad-spectrum systemic antiviral agent with therapeutic potential

This paper is a lot like the DRACO paper, actually. Neat data from tissue culture, plus some neat data from animal models, but still a long way from any kind of human therapy.

Squalamine might work by changing the static charge of cell membranes. Change the charge, change a viruses ability to interact with proteins in the cell membrane, and to assemble babby viruses at the cell membrane, theoretically.

Because this drug would, most likely, be introduced IV, and anything in your blood gets run through your liver, these scientists focused on viruses that infect the cells lining your blood vessels and the liver-- dengue, yellow fever, eastern equine encephalitis virus, CMV (mouse version), and Hepatitis B and D.

Their tissue culture work looked promising, so they moved to animal models, which also look promising. They actually look very promising, because they arent perfect. They dont look 'too-good-to-be-true'. It kinda looks like real data that we could improve upon with further research, or further interventions in a human setting.

For instance, EEEV:

EEEV is an enveloped RNA virus of the Alphavirus family genus in the family Togaviridae for which neither an effective antiviral drug nor a licensed human vaccine is available (50). The case fatality rate is between 30% and 80% for humans and up to 95% for horses, and EEEV is regarded as a potential biodefense threat (51).

EEEV causes widespread vascular disease in the hamster, involving all of the major organs (42). Infection of the vasculature of the brain followed by direct infection of neuronal cells results in fatal encephalitis.

You might not have heard of EEEV before unless you are a horse person, but it is no joke in humans. And its not this mystical magical disease that you only get in some scary jungle in South East Asia or from some scary bug in Africa-- it kills right here in the good 'ol USofA.

In their animal model, all of the hamsters infected with EEEV died. You could take that as 'Shit. Didnt work.' Or, you could take it as 'The EEEV + squalamine hamsters lived twice as long as the hamsters that didnt get squalamine. In the real world, a horse or a human infected with EEEV would have a lot of external medical support not provided to the hamsters. Considering we have nothing to help EEEV infected humans and horses, squalamine might actually give us a snowballs chance in hell of saving someone/thing.'

Rarely does one thing work in isolation from all other things, especially when you are dealing with severe/violent illnesses. We need lots of things working together to save people. Squalamine might be part of the equation in ten years. Or it might be just one of those things that looked promising and never panned out.

But it is pretty cool we originally found this chemical in shark guts, and now we can make it from soybean guts. Whoda thunk it?

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I was at a NERCE conference today and saw one of the DRACO guys was giving a poster. Cool data - works at low concentration and for tons of viruses.

But somehow the idea of using an enormous recombinant protein at the dose needed for a systemic injection strikes me as a long shot - though it could be great for hospitals to have in their toolkit as a last-ditch method.

The fact that the word "Panacea" was used in the poster title without any sense of irony was a bit of a turn off though.

Triple e is always a threat here in MA during warm weather...

I hope alot of this pans out..but I have a nagging doubt about it all...probably because of my lack of education tho!

Having used squalamine in the past, for the purpose of screwing up membrane charge, I'm dubious about its use as a therapeutic. Its horrifically non-specific, and to date every clinical trial using it has been ended - often early, due to side effects.

AFAIK, the only trials with success are ones using it locally - i.e. the on-going trials for ocular degeneration.

Its a cool compound from a research point of view, but any drug which knocks dozens of intracellular proteins off of the PM in every cell it encounters is bound to be problematic. You should see the cells squirm, under the scope, when you drop squalamine on then.

Bryan

Hmph, my original post is pending moderation. The above link is to a piece in Science talking about the XMRV saga and a 9-lab collaboration which (not surprisingly) failed to find XMRV. Anyway, I figured since one of the authors retracted his part of the original paper, I figured it'd be worth sharing. Hopefully this will make my above post make more sense until the previous one is OK'd

By Poodle Stomper (not verified) on 23 Sep 2011 #permalink

Oh, this is helpful. I've been trying to find an article on squalamine and how it works as an antiviral. I'm still interested in it even though it's yet to be potential for human therapeutic use. Thanks ERV