A picture that shows the SARS-CoV-2 spike and cell attachment cell

The dinner party bores who once so confidently proclaimed hanging chads (2000) and subprime mortgages (2008) now have a new way of proclaiming their sagacity: “Ah, but what about the furin cleavage site? A smoking gun, if you ask me. ‘

It would be as if the Chatterati were suddenly obsessed with the intricacies of aromatic substitution or heterogeneous catalysis. I admit that I would have previously thought furin was a derivative of the furan molecule when in reality it is an enzyme that does the job of converting freshly synthesized proteins into their active form – a job done by splitting off bits of the precursor proteins is carried out.

Here, of course, everything revolves around Covid – specifically, the point in the spike protein of the Sars-CoV-2 coronavirus that has been cut off by furin (or related protease enzymes). This transformation enables the spike protein to bind to the ACE2 receptor of human cells, thereby initiating viral attachment and infection.

A controversial side

It has been known for about a year that this step is central to the way the virus attacks.1-3 But what has brought this biochemical reaction to public awareness is the suggestion that something looks rotten at this furin cleavage site (FCS) – or rather, it doesn’t look good enough. The original view was that the causative agent of the pandemic was a natural virus that spread from bats to humans in China, possibly via Wuhan’s meat markets. However, some now suspect that one or the other FCS from Sars-CoV-2 was developed in a laboratory – most likely in the Wuhan Institute of Virology. American biologist David Baltimore, who received the Nobel Prize in 1975 for his work on the virology of cancer, put the cat among the pigeons by saying: New York Times Reporter Nicholas Wade that the coronavirus FCS is a “smoking weapon” due to its laboratory origins.

This laboratory leak hypothesis suggests that the virus could have been either an innocent but risky experiment that went wrong or a virus deliberately tailored to infect and kill people. However, such gain-of-function experiments, which give viruses new, manipulated capabilities, are known to be carried out in many countries. All the more explosive about the laboratory leak hypothesis is that some gain-of-function studies in Wuhan appear to have been funded in part in collaboration with researchers in the United States – which may make the idea embarrassing for both China and its global economic rival.

As if that weren’t bad enough, at the start of the pandemic, the Trump administration pushed the lab leak theory, initially without credible evidence, to divert attention by fueling xenophobic anti-Chinese sentiments. It likely helped provoke anti-Asian abuse and attacks and tarnished the idea as a racist conspiracy theory. Chris Ford, former assistant secretary of state for international security, has indicated that Trump’s State Department was not so much investigating the argument that Sars-CoV-2 was a Chinese bio-weapon that had escaped, but was actively constructing this case.

It is one of the few divisive controversies of the pandemic that has not split neatly along politically partisan lines

This explains in part why the resurgence of the lab leak theory has become poisonous through and through – despite being one of the few divisive controversies of the pandemic that has politically not split cleanly. Lab-leak advocates accuse both China and some in the US of suppressing any serious investigation, either out of self-interest or out of political correctness; their opponents continue to see the idea as fundamentally racist and without solid evidence.

What is special about the FCS? Such a trait is found in other coronaviruses isolated from the wild4th – but apparently not in all where there is more than 40% sequence agreement with the Sars-CoV-2 spike protein.5 It has other unusual structural features and, in addition, the modification of the FCS is a common place for functional reinforcement experiments.6.7 But who are we to say what evolution could bring about? Isn’t this an argument out of disbelief, like the intelligent design view that the eye or the flagellar motor are improbable products of natural selection?

Baltimore has now withdrawn its comment on the “smoking gun”, saying that it has not yet disregarded the laboratory leak theory.8th Neither do US President Joe Biden – and neither do we. However, an honest assessment must also recognize that there is no direct evidence for this either. We may never know the truth for sure, especially given China’s reluctance to allow international control. That an international scandal – perhaps even a crime – of such dire proportions should be imputed to a quartet of amino acid residues is one of the more bizarre facets of the pandemic. Perhaps it is more productive to look at the FCS not as a window to the origins of the pandemic but to the virus itself: how it works and how we could thwart it.9

References

1 S Xia et al, Signal converter. Aim. There.,2020.5, 92 (DOI: 10.1038 / s41392-020-0184-0)

2 TP peacock et al, Nat. Microbiol., 2021, DOI: 10.1038 / s41564-021-00908-w

3 BA Johnson et al, bioRXiv, 2020, DOI: 10.1101 / 2020.08.26.268854

4 Y Wu and S Zhao, Stem cell res., 2021,50, 102115 (DOI: 10.1016 / j.scr.2020.102115)

5 D Wang et al., Anal. Chem. No., 2020,92, 14730 (DOI: 10.1021 / acs.analchem.0c03301)

6 R Segreto et al., Environment Chem. No. Latvian.,2021, DOI: 10.1007 / s10311-021-01211-0

7 AR Romeu and E. Ollé, Forms, 2021, 2021020264 (DOI: 10.20944 / preprints202102.0264.v1)

8 A Maxmen and S Mallapaty, nature, 2021, 594, 313 (DOI: 10.1038 / d41586-021-01529-3)

9 BA Johnson et al., nature, 2021,591, 293 (DOI: 10.1038 / s41586-021-03237-4)

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