YEAH, BUT HUNTER'S LAPTOP!:

SARS-CoV-2 is a member of a subgenus of the betacoronaviruses called the sarbecoviruses, named after their prototype member, SARS-CoV-1, which caused the SARS epidemic in 2002 and 2003. The zoonotic origin of SARS-CoV-1 has been firmly established by research that also showed that the bat sarbecoviruses pose a clear and present danger of pandemic overspill from bats to humans.

One key feature of sarbecoviruses is that they undergo extensive amounts of recombination. Parts of their genomes are being regularly swapped at a rate that implies a vast ecosystem of these viruses is circulating, most of which have not been discovered. The area of the genome that is most likely to recombine is also the area that encodes the "spike" proteins--the very proteins that play a crucial role in initiating an infection. Many sarbecoviruses encode spike proteins that can bind to a wide range of mammalian cells, suggesting that these viruses can easily move back and forth between different species of mammals, including humans.

SARS-CoV-2 is not as virulent as SARS-CoV-1, but it is transmitted far more easily between people. Two of the most prominent features of the SARS-CoV-2 spike are its receptor-binding domain (RBD), which binds very tightly to human ACE2, the protein that allows it to enter lung cells, and the so-called furin cleavage site (FCS). This site divides the spike protein into subunits. The FCS is present in many other coronaviruses, but so far SARS-CoV-2 is the only sarbecovirus known to include it. It allows the viral spike protein to be cut in half during its release from an infected cell, priming the virus to spread to new cells more efficiently.

The RBD and FCS are central to initial virological arguments by expert proponents of the lab-leak hypothesis. Such arguments are based on the supposition that neither the RBD nor the FCS "appears natural" and therefore that they can only be the product of lab-based engineering or selection. Nobel laureate David Baltimore, an early proponent of the lab-leak hypothesis, referred to the FCS as a "smoking gun" that points to a lab origin. [...]

Recently, for example, bat colonies on the border between Laos and China were discovered to carry sarbecoviruses that have RBDs almost identical to those of SARS-CoV-2 in both sequence and ability to enter human cells. This finding refutes the claim that SARS-CoV-2's binding affinity in humans is unlikely to have a natural origin.

Similarly, although some lab-leak proponents contend that the lack of an FCS in the closest relatives of SARS-CoV-2 is indicative of its manual insertion in a lab, very recent evidence from SARS-CoV-2 population sequencing suggests that the insertion of new sequences from human genes next to the FCS can be detected. Moreover, the closest relative of the SARS-CoV-2 spike in the Laotian bat viruses would require the addition of only a single amino acid to generate a putative FCS. Thus, in a species where it would have a major selective advantage, it would probably be very easy for some of these bat coronaviruses to rapidly evolve an FCS.

This research sketches a clear zoonotic path to the emergence of the RBD and FCS. Although some evolutionary gaps along this path persist, their number and size have been dwindling. A detailed analysis in late 2021 further strengthened the link to the Huanan markets as the point of origin of the virus and the initial source of community transmission. This rapidly growing body of evidence for a zoonotic origin of SARS-CoV-2 creates increasing difficulties for the lab-engineering hypothesis.

In normal scientific inquiry, as evidence emerges, the remaining space for plausible hypotheses narrows. Some facets continue to be supported, and others are contradicted and eventually precluded altogether. Some of the strongest advocates for a lab origin for SARS-CoV-2 changed their views as they learned more. Baltimore, for instance, withdrew his "smoking gun" comment when challenged by additional evidence, conceding that a natural origin was also possible. Revising or rejecting failed hypotheses in light of refuting evidence is central to the scientific process. Not so with conspiracy theories and pseudoscience. One of their hallmarks is that they are self-sealing: as more evidence against the conspiracy emerges, adherents keep the theory alive by dismissing contrary evidence as further proof of the conspiracy, creating an ever more elaborate and complicated theory.

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