The Origins of Sars-CoV-2

August, 2023

The key issue is the origin of SARS-CoV-2, the virus that causes COVID-19, and whether it evolved naturally or was the result of laboratory manipulation.

Endonuclease fingerprint indicates a synthetic origin of SARS-CoV-2

Scientists can make a copy of a virus in a lab, sort of like how you can build something with LEGO blocks. To do this, they use special tools called enzymes, which are like tiny LEGO separators, to cut up the DNA, which are like the instruction manuals for building a virus. Once they have the pieces, they can put them together to make a new virus. These pieces have special markers, kind of like labels, which can show if a virus was made in a lab or if it comes from nature.

The Endonuclease fingerprint study is saying that the coronavirus, SARS-CoV-2, has these special labels that usually only show up in viruses made in a lab. The way these labels look in SARS-CoV-2 is not how they usually look in viruses found in nature. So, the researchers think it's very likely that this virus was made in a lab, not something that occurred naturally.

But other people said, "Wait a minute, let's test if these special Lego pieces are really that special." They suggested a way to check and found that these 'special' Lego pieces actually appear in other Lego castles that we know weren't tinkered with. So, the original idea that these were 'special' clues pointing to a lab-made virus might be wrong.

The proximal origin of SARS-CoV-2

• Point: All previous human coronaviruses have zoonotic origins, and SARS-CoV-2 bears several signatures of these prior zoonotic events.
  • Strength: It uses historical evidence and patterns of other coronaviruses as a foundation, providing strong circumstantial support for a zoonotic origin of SARS-CoV-2.
  • Weakness: This argument is based on precedent and does not provide direct evidence specifically regarding the origin of SARS-CoV-2.
• Point: SARS-CoV-2 displays clear similarities to SARS-CoV that spilled over into humans from markets selling live animals.
  • Strength: Establishes a parallel with another known zoonotic transmission event, lending credence to a similar pathway for SARS-CoV-2.
  • Weakness: Again, this argument relies on comparison rather than providing direct evidence for SARS-CoV-2’s zoonotic origin.
• Point: Epidemiological data link the Huanan market in Wuhan to early and major epicenter of SARS-CoV-2 infection.
  • Strength: This point provides direct, geographic evidence linking the early spread of the virus to a known wildlife market.
  • Weakness: It does not prove that the virus originated at the market, only that it was a significant site of spread. Early cases with no direct link to the market are not fully explained.
• Point: SARS-CoV-2 was detected in environmental samples at the Huanan market, primarily in sections trading in wildlife and domestic animal products.
  • Strength: This evidence directly connects the virus to a location where wildlife and domestic animals were sold, supporting a zoonotic hypothesis.
  • Weakness: It's possible that the virus was brought to the market by infected people rather than originating from animals at the market.
• Point: The earliest split in the SARS-CoV-2 phylogeny defines two lineages that likely circulated contemporaneously, suggesting multiple spill-over events.
  • Strength: Genetic evidence like this can provide very strong support for the hypotheses about the emergence and initial spread of the virus.
  • Weakness: Without further evidence, it's hard to determine whether the split represents different zoonotic events, adaptation to human hosts, or other factors.
• Point: Viruses closely related to SARS-CoV-2 have been documented in bats and pangolins in multiple localities in South-East Asia.
  • Strength: This evidence connects the virus to specific animals and regions, providing a potential pathway for zoonotic transfer.
  • Weakness: The genetic distance between these viruses and SARS-CoV-2 is significant, indicating a gap in the zoonotic transmission chain that hasn't been filled.
• Point: No bat reservoir or intermediate animal host for SARS-CoV-2 has been identified to date.
  • Strength: An honest acknowledgement of the current limitations in understanding and evidence.
  • Weakness: This point highlights a major gap in the zoonotic hypothesis that needs to be filled to provide a comprehensive explanation for the origin of SARS-CoV-2.

Points For Laboratory Origin of SARS-CoV-2:

• Point: Precedents exist for laboratory incidents leading to isolated infections and transient transmission chains.
  • Strength: Historical data corroborates the fact that lab leaks have occurred in the past.
  • Weakness: This point is not specific to SARS-CoV-2 and does not provide direct evidence that the virus originated in a lab.
• Point: The Wuhan Institute of Virology (WIV) possesses an extensive catalog of samples derived from bats, including three SARS-related coronaviruses (WIV1, WIV16, Rs4874).
  • Strength: The fact that WIV has worked with similar viruses increases the feasibility of a potential lab leak.
  • Weakness: Merely possessing similar viruses does not provide direct evidence of SARS-CoV-2 originating in a lab.
• Point: WIV has reportedly successfully cultured these SARS-related coronaviruses.
  • Strength: The ability to culture SARS-related coronaviruses indicates the technical capabilities for potential mishandling.
  • Weakness: Successfully culturing other coronaviruses doesn't indicate that SARS-CoV-2 was cultured or accidentally released.
• Point: A specific scenario postulated is the accidental infection during serial passage of a SARS-related coronavirus in common laboratory animals.
  • Strength: This provides a potential mechanism for how a lab leak might occur.
  • Weakness: This is a hypothetical scenario and doesn't offer direct evidence of a lab leak of SARS-CoV-2.

Points Against Laboratory Origin of SARS-CoV-2:

• Point: All documented laboratory escapes have been of readily identifiable viruses associated with sustained work in high titer cultures. There's no data to suggest WIV was working on SARS-CoV-2, or any virus close enough to be the progenitor, prior to the pandemic.
  • Strength: There's no evidence that WIV was working with SARS-CoV-2 or a very similar virus prior to the pandemic, decreasing the likelihood of a lab origin.
  • Weakness: Absence of evidence is not evidence of absence. The possibility of undisclosed work cannot be entirely ruled out.
• Point: No cases of laboratory escape have been documented following the sequencing of viral samples.
  • Strength: This suggests that the risk associated with sequencing activities is minimal.
  • Weakness: This statement is based on historical precedents and does not rule out the possibility of a future occurrence.
• Point: Despite extensive contact tracing, no cases related to any laboratory staff at the WIV have been reported, and all staff were said to be seronegative for SARS-CoV-2 when tested in March 2020.
  • Strength: This provides direct evidence against a lab origin, as any accidental release likely would have infected lab workers first.
  • Weakness: It relies on the completeness of contact tracing and the accuracy and transparency of reporting, which may be limited.
• Point: Early SARS-CoV-2 isolates were unable to infect wild-type mice, inconsistent with a virus selected for increased pathogenicity and transmissibility through serial passage through susceptible rodents.
  • Strength: This supports the idea that the virus was not being manipulated in the lab for research purposes, as it was not initially able to infect a commonly used laboratory animal.
  • Weakness: It doesn't rule out the possibility that the virus was being manipulated in ways that don't involve increasing its pathogenicity or transmissibility in mice.
• Point: No genomic markers associated with rodent adaptation are found in SARS-CoV-2, indicating it's highly unlikely to have been acquired by laboratory workers in the course of viral pathogenesis or gain-of-function experiments.
  • Strength: The absence of expected genetic markers provides strong evidence against the hypothesis that the virus was being manipulated in a lab.
  • Weakness: This statement relies on our current understanding of viral genetics and evolution, which is not comprehensive.