Day 123: Made in a Lab

In a fortunate moment of insomnia, one of PlagueBlog's vast team of reporters spotted a 338-page preprint on Reddit about how SARS-CoV-2 was engineered in a lab. The reporter was only a few pages into this fascinating read when the moderators found it and scrubbed it from Reddit—but not from viXra.org, an unmoderated preprint server set up to avoid censorship at arXiv.org. The paper, by graduate student Murat Seyran, is titled Host Change -Tropism [sic] Pattern of Human Coronaviruses Suggesting the Engineered Nature of Severe Acute Respiratory Syndrome Coronavirus 2.

Most of the 338 pages are the supplementary materials, including some nice tables comparing various coronavirus sequences, plus 7 less approachable sets of sequence alignment results that don't really fit the page format. The text itself is quite readable at only 15 pages, and nicely summarizes the seven known human coronaviruses and the (ongoing) changes from their animal sources that make them infective in humans. It's worth a read just for that, even if you're uninterested in the question of whether SARS-CoV-2 was bioengineered.

So what is suspicious about SARS-CoV-2? One issue is a change that didn't happen that normally does during coronavirus adaptation to humans:

[The] N-terminal domain (NTD) of CoVs Spike (S) Protein contains a specific glycan-binding region as the first contact area with the new host. Specific glycan-binding immune receptors e.g. C-type lectins recognize NTD of S Protein of CoV and exterminate the virus before its adaptation. [...] Strikingly, SARS-CoV-2 does not have a single amino acid (aa.) alteration or deletion on its glycan-binding region NTD of its S Protein compares to its parent virus BatCoV RaTG13. The flat and unsunken surface of SARS-CoV-2 NTD S Protein conflicting with the general adaptation and survival pattern of all CoVs.

And that's only the first difference of three. The second is that a "template-switching" model of coronavirus replication restricts mutations to certain sites. ("CoVs pause their replication on certain domains and have recombinations on these specific sites.") However, the second major mutation of SARS-CoV-2 involving the virus' use of host cell furin protease is not at one of these sites, and that suspiciously altered site continues to stubbornly not mutate in the wild:

However, other betacoronavirus lineage B members and the clinical strains of SARS-CoV-2 do not have any alterations on S Protein S1/S2 suggesting SARS-CoV-2 obtained this trait with a one-time unique event.

The third suspicious trait is similar; coronaviruses generally continue to adapt to the host in certain positive selection sites, including the receptor binding domain (RBD).

However, despite millions of SARS-CoV-2 infections, RBD has not indicated a single high-frequency aa. substitution suggesting the too-perfect angiotensin-converting enzyme 2 (ACE2) binding that was gained with a one-time alteration. Unlike the RBDs of other CoVs, SARS-CoV-2 RBD is not a positive selection site.

Besides the purely biological arguments, the author has some other evidence to bring to bear for bioengineering. Firstly, engineering coronaviruses was all the rage before a US moratorium on such research, and, possibly, afterwards. Secondly, coronaviruses are postulated to spread to humans through bat and camel droppings polluting the water supply, but China's bat diversity is relatively low and its water supply relatively safe from such issues.

The author concludes with a series of rhetorical questions reflecting what has come before:

The engineered origin of the SARS-CoV-2 was mainly rejected (Andersen 2020) the question is how SARS-CoV-2 survived the immunity of pangolins or humans during the very first interaction with its flat easy-target sialic acid-binding domain? SARS-CoV-2 indicate the low frequency of mutations on its RBD and how the virus obtained such effective RBD compositions without destroyed by pangolin or human immunity due to its easy target sialic acid-binding domain? Why only the RBD had mutations meanwhile the rest of the genome was almost unaltered? Betacoronavirus lineage B CoVs including SARS-CoV S Protein does not have a pattern of recombination on S1/S2 region how SARS-CoV-2 obtained that ability and how we do not see any further recombinations in the clinic SARS-CoV-2 strains? SARS-CoV-2 clinic strains do not have any high-frequency mutations on NTD and RBD how the virus obtained such perfect and precise host cell membrane interaction capacity, unlike SARS-CoV, perished due to its failed adaptation? Why we have not seen any pandemic caused by CoVs before? Why these pandemics did not emerge in places where people rely on water sources shared with bats or bats consumed as bushmeat? In summary, if SARS-CoV-2 is not an engineered Bat CoVs RaTG13, its unnatural host tropism pattern and pandemic potential compare to other human pathogenic CoVs raising those questions.

It's interesting that the author is suspicious of SARS-CoV-2 despite accepting the bat coronavirus BatCoV RaTG13 as its natural ancestor, because other made-in-a-lab theories are equally, if not more, suspicious of RaTG13 itself.

If you follow the conspiracy theories, you have probably heard of "batwoman" Zhengli Shi, a researcher from the Wuhan Institute of Virology who allegedly discovered RatG13 in 2013, although the sequence was not published until this January as part of a COVID-19 paper and (so the conspiracy theory goes) the samples may not be extant, if they ever were. (The alternative hypothesis is that the sequence was invented as a missing link to conceal the engineered nature of SARS-CoV-2.) Instead, the postulated ancestors of SARS-CoV-2 are BatCoV ZC45 and BatCoV ZXC21, plus Zhengli Shi. The similarities are explained at both the link above and in the related blog post.

If you're interested in more mainstream reporting on viral origins, ArsTechnica investigates a two-species origin theory, in which a pangolin takes on the role of Zhengli Shi. The source paper is here, with plenty of analysis of BatCoVs RaTG13, ZC45 and ZXC21, plus some PanCoVs.

PlagueBlog does not endorse any particular origin theory for SARS-CoV-2.

P.S. Massachusetts cases are up 0.36% today (probable cases included).

On the tin-pot mayors vs. state and federal constitutions front, a New Hampshire resident is suing the city of Nashua in Hillsborough County Superior Court South over face mask requirements exceeding those of the state.

In the lawsuit, Fojo argues that the city has failed to explain why its health officials are not heeding the guidance of the World Health Organization.

"The ordinance’s justification that 'slowing the spread' of the coronavirus is somehow still a societal objective also ignores the fact that the entire state of New Hampshire has been wildly successful at 'flattening the curve' since it never came close to reaching the capacity of its health care system," the complaint states.