Scientist James Lyons-Weiler Weighs in on Snake Venom Theory

Guest Post by James Lyons-Weiler, Ph.D.

Scientist James Lyons-Weiler, Ph.D., said at least 10 people asked him about the snake venom proteins in relation to COVID-19. He proposed two possible explanations, one of which he favors over the other.

Dr. Meryl Nass said the snake venom stuff is “hooey.” My analysis says yes, let’s move on to more productive pathways.

I share two possible explanations for their presence in COVID-19 patients, one of which I favor over the other.

Snakes were first floated as a potential intermediate host organism by a very early speculative report covered by SciAm in Jan 2020 that found codon usage bias most similar to snakes of all things.

Codon usage bias is determined by the percentage of times specific codons (triplet nucleotides) are used to bring specific amino acids in place in protein sequences.

It’s suggestive, but very, very weak and has not been taken seriously by anyone as sufficient evidence indicating snakes were the intermediate hosts.

Reading the 2021 venom paper cited by Bryan Ardis, here is my breakdown:

In Italy, with 20 COVID-19 samples and 10 control (non-COVID-19 patients), 5 plasma samples from COVID-19 patients and 3 fecal samples had evidence of proteins of unknown origin detected using a protein assay that led to the finding of animal venom proteins in their blood or feces.

They sequenced the proteins and found multiple types of venoms, including snake venom proteins.

That’s it. It’s a small study.

Here’s one amino sequence from their study that seems to share similarities across many of the venom types from different animal species:

MKLVLAIVLILMLVSLSTGAEESGQEISMVGPPLYIWDPIPPCKQLDEDCGYGYSCCEDLSCQPLIEPDTMEITALVCQIESA

(Learn how to analyze DNA and RNA sequences this summer in our Bioinformatics class at IPAK-EDU taught by yours truly.)

This polypeptide has only a single match in all of the trees of life. It matches a toxin from Conus pulicarius. Here’s a photo:

Conus pulicarius, a common name the flea-bitten cone, is a species of sea snail, a marine gastropod mollusk in the family Conidae, the cone snails and their allies. (Source: Wikipedia).

The distribution of this sea snail is: Central and Western Pacific; Polynesia (not Marquesas); Cocos (Keeling) Island, New Guinea and Australia (Northern Territory, Queensland and Western Australia).

So the study found venom proteins in patients in Italy from animals other than snakes, and those in snakes and the sequences of these venoms are all pretty similar to each other.

The match is 100% and extends over the full length of the sequence.

Pretty good match, I’d say.

But — that’s because it’s a match — to itself.

This protein does not match any SARS-CoV-2 proteins. Neither do any of the other venom proteins.

The study actually has no evidence and makes no claim of these polypeptides being encoded by the SARS-CoV-2 virus. It only reports that the venom proteins were found in SARS-CoV-2 patients, but not controls.

Metabolites?

Here’s a link to a news article about a study that says that metabolites in COVID-19 patients — products of the human body — can be toxic and can be like snake venom.

Here’s a link to the same story, but from a different source.

And, here’s a link to the study they reference on the human secretory phospholipase A2.

Does this mean the human body produces venom in response to SARS-CoV-2 infection?

There is no match between the human secretory phospholipase A2 protein.

Animal venoms as treatments for autoimmunity?

Now check this out, some studies are finding venoms, including snake venoms, can reset the CD4/CD8 imbalance seen in serious cases of COVID-19:

“Many toxins are multifunctional and have several biological targets which may have no relation with their toxic role. Some toxin-derived peptides are now being used to treat type 2 diabetes, hypertension, neuropathic pain, and other medical disorders.

“Some data confirm the effect of bee venom (BV) on preventing COVID-19 and improving it [1]. Some other data ignore the BV effect on preventing COVID-19 and hypothesize that less SARS-CoV-2 infection in beekeepers is due to their less exposure to other people [3].

“A low dose of botulinum neurotoxin (BoNT) can reduce the symptoms of COVID-19, and so, it could be used in treatment lines [14]. It has demonstrated that the rate of DTP vaccination has an inverse correlation with COVID-19 prevalence [15].

“Cobrotoxin has an anti-inflammatory effect and also can restore the CD4/CD8 ratio and perform immunoprotective activity against SARS-CoV-2 [16]. Tetrodotoxin is an inhibitor of MPro of SARS-CoV-2 and so can affect the virus [17].”

Some relevant questions:

1. Five control samples are too few. How many people w/out COVID-19 have the protein in their blood or feces?
2. Were these patients treating themselves (or under the care of doctors) for COVID-19 (or another autoimmunity) with animal venoms?

We know that patients with severe COVID-19 most likely already had autoimmunity. It’s about 80% in severe COVID-19 with autoimmunity compared to about 8% in mild COVID-19. That’s a huge difference in the prevalence of autoimmunity associated with COVID-19 outcomes.

My favored hypothesis is that autoimmune patients in Italy using animal venoms to treat their autoimmunity — or to ward off COVID-19 — have confused the heck out of scientists who find those venoms or metabolites thereof in their feces and blood.

But it’s also possible that we produce proteins in response to SARS-CoV-2 infection that match venom in other species. Unlikely, but I can’t rule it out.

Here’s an article on Venom Immunotherapy from Brazil with extensive citations of studies of venom proteins to treat autoimmunity.

Remember, SARS-CoV-2 was touted as “everyone is going to die” — and the link between prior autoimmunity and serious SARS-CoV-2 is very, very strong.

I’d be curious to learn if anyone has any leads on the prevalence of animal venom injections in use to either treat autoimmunity or attempts to treat COVID-19 in Italy.

If you consume snake venom… well, it’s a protein, and knowing what happens to proteins in our stomachs is just an internet search away.

I don’t have a definitive answer but I know the venom has to be injected or produced endogenously to be found in the blood or feces of anyone.