New York Times posted:

Why all the dismissals?
It appears to be a classic example of groupthink, exacerbated by partisan polarization.

Global health officials seemed unwilling to confront Chinese officials, who insist the virus jumped from an animal to a person.

In the U.S., one of the theory’s earliest advocates was Tom Cotton, the Republican senator from Arkansas who often criticizes China — and who has a history of promoting falsehoods (like election fraud that didn’t happen). In this case, though, Cotton was making an argument with plausible supporting evidence.

The media’s coverage of his argument was flawed, Substack’s Matthew Yglesias has written. Some coverage exaggerated Cotton’s comments to suggest he was claiming that China had deliberately released the virus as a biological weapon. (Cotton called that “very unlikely.”) And some scientists and others also seem to have decided that if Cotton believed something — and Fox News and Donald Trump echoed it — the idea had to be wrong.

The result, as Yglesias called it, was a bubble of fake consensus. Scientists who thought a lab leak was plausible, like Chan, received little attention. Scientists who thought the theory was wacky received widespread attention. It’s a good reminder: The world is a complicated place, where almost nobody is always right or always wrong.

just slipped and did a groupthink, whoopsie — but that tom cotton, he was the maverick who resisted it!

as long as we're boldly challenging consensuses, i guess i can count on renewed calls from our rulers to investigate those claims that it was detected in wastewater samples collected in March 2019 in Barcelona, or that blood samples given by volunteers for a cancer screening trial in Milan in Sept 2019 were found to contain SARS-CoV-2 antibodies

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969828/ posted:

1.1. SARS-CoV-2: the man-made virus theory

The origin of SARS-Cov-2 is still passionately debated since it makes ground for geopolitical confrontations and conspiracy theories besides scientific ones. The first hypothesis is that of a man-made virus raised first by Pradhan and colleagues who claimed to have observed the presence of HIV sequences in SARS-CoV-2, before retraction of the manuscript and then by Perez and Montagnier (2020). This hypothesis was rebutted by bioinformatic analyses showing that the similarity of those short putative HIV insertions was insufficient to support a common ancestral origin of the sequences (Liu et al., 2020c; Xiao et al., 2020b). This article has since then been retracted. Furthermore, the four insertions identified in SARS-CoV-2 occurred independently at different times of coronaviruses diversification (Sallard et al., 2020). Other hypotheses were based on the construction of infectious recombinant SARS-CoV capable to replicate in mammalian cell lines or animal models (Becker et al., 2020; Menachery et al., 2020). Before retraction of their manuscript, Pradhan et al. also claimed that the RBD of SARS-CoV-2 might have been engineered by using a RBD domain with a higher affinity for the human ACE2 receptor and by inserting the RRAR furin cleavage site downstream of the RBD, making the virus more infectious in human cells. This hypothesis was mostly motivated by the fact that this furin cleavage site is unique to SARS-CoV-2 among all Sarbecoviruses (Andersen, 2020; Coutard et al., 2020). However, the supposedly engineered sequences were simply natural features (Liu et al., 2020c; Andersen, 2020; Hao, 2020; Othman et al., 2020). Furthermore, naturally occurring polybasic furin cleavage sites have been described in other lineages of coronaviruses such as MERS-CoV, HKU1, HCoV-OC43 or IBV (Andersen et al., 2002; Huang et al., 2006; Yamada and Liu, 2009) and is a common feature in viral envelope glycoproteins (Hao, 2020; Dimitrov, 2004). The natural occurrence of furin-cleavage sites in various viruses has been documented for long. We provide a list of 50 selected references as Supplementary Data. Some linked the presence of the least preferred CGG codons in the SRAS-CoV-2 furin cleavage sites as a “proof” of engineering. A codon being least preferred does not mean it should never exist and this CGG codon present in SARS-CoV-2 is for instance present at a higher rate in MERS-CoV (Chen et al., 2017; Hou, 2020). The lower presence of CpG (intrachain Cytosine-Guanosine dinucleotide linked by a phosphate bond) in human pathogens has been shown to be a selective process. CpGs trigger direct B-Cell activation and therefore these dinucleotides provide a selective disadvantage (Krieg et al., 1995). However, they nevertheless exist in human pathogens. When considering the huge selective advantage in transmissibility brought by the furin-cleavage site and the disadvantage brought by the B-cell activation, the net result in largely in favor of the furin-cleavage site leading to the fixation of these mutations in the human populations even if it involves the rare CGG codons. This is a simple and straightforward selective and evolutionary process. RmYN02 also carries an indel at the same place as the furin site (PRRA) indel of SARS-CoV-2 with the insertion of a PAA sequence and the deletion of the immediate QTQT upstream sequence (Zhou et al., 2020b). The naturally occurring PAAR sequence displayed by RmYN02 is not active as a furin-cleavage site but is only one mutation away from the active RNNR furin cleavage site. One additional mutation turning the proline (P) into an arginine (R) will generate a RAAR active furin-cleavage site. This suggests that viruses other than SARS-CoV-2 were under similar selective pressure. The selection of SARS-CoV-2 through successive passages in cell culture was refuted (Andersen et al., 2020). Scientists at the Wuhan Institute of Virology denied having carried out engineering and gain of function experiments on SARS-CoV-2but only on SARS-CoV in published and openly displayed international collaborations (Cohen, 2020). Altogether, these elements indicate that there is no evidence to support the hypothesis of a man-made origin of SARS-CoV-2.

1.2. SARS-CoV-2: the bat-pangolin recombinant virus theory

The next hypothesis to consider is the natural origin of SARS-CoV-2 as a recombinant between a Sarbecovirus from Malayan pangolins and RaTG13 from R. affinis. This hypothesis found its rationale in the in-silico analysis of sequence similarities which indicated that SARS-CoV-2 was closely related to RaTG13 but displayed specific RBD sites similar to the pangolin virus (Xiao et al., 2020a; Zhang et al., 2020b; Li et al., 2002; Lam et al., 2020). However, this recombination theory was dismissed, too many misalignments being present (Boni et al., 2020; Paraskevis et al., 2020; Chen et al., 2020). Furthermore, the detection of recombination was deduced from metagenomic data, an approach which can by itself generate artifactual recombinants. The recombinant hypothesis implies that both viruses must be at the same time in the same host cell. Not only R. affinis and pangolins do not share the same habitat, but no Sarbecovirus was isolated or detected in Chinese pangolins, Manis pentadactyla (Xiao et al., 2020a). R. affinis bats from China and from the Indomalayan region belong to two different subspecies, R. affinis affinis and R. affinis superans, respectively (Ith et al., 2015). The northern most limit of R. affinis superans is Southern Thailand (Ith et al., 2015). The RaTG13 virus was detected in an anal swab sample of a R. affinis bat in Yunnan (Ge et al., 2016; Cohen, 2020) whereas Sarbecoviruses were exclusively found in Malayan pangolins, M. javanica, smuggled from the Indomalayan region (Xiao et al., 2020a; Lam et al., 2020; Liu et al., 2019). No Sarbecovirus was detected in 334 Malayan pangolins confiscated by the Malaysian customs (Lee et al., 2020). Furthermore, SARS-CoV-2 is phylogenetically branching at an ancestral level to Sarbecoviruses from pangolins, making it impossible to be a descendant from recombination (Wenzel, 2020). The question is therefore whether the infected Malayan pangolins were natively infected or were they instead infected during the smuggling process through contact with humans or other animals? A similar analysis was performed for SARS and MERS (Frutos et al., 2021). There are currently only in silico predictions from metagenomic data and no factual element to support the recombinant hypothesis.

1.3. SARS-CoV-2: a naturally occurring virus

The only remaining rational option for the origin of SARS-CoV-2, is that of a naturally occurring virus circulating in the wild which came into contact with humans. However, there is still no information on where and when this contact with humans occurred at the first place. An extensive mutational bias is introduced by the host APOBEC (Apolipoproteins B mRNA editing enzyme, catalytic polypeptide-like) RNA editing system. The extensive APOBEC-driven mutational bias and adaptation suggest that SARS-CoV-2 might have circulated unnoticed in humans for a long time (Matyasek and Kovarik, 2020; Zhan, 2020), but molecular clocks indicate instead a recent introgression into humans (Lai, 2020; Zehender et al., 2020). However, the Sarbecoviruses genome is saturated with transition/transversion (Ts/Tv) ratios of 1 or below 1 for the RdRp and spike genes (Frutos et al., 2021). This indicates that the genome is highly mutated and that the linear mutation/time relationship on which molecular clock analyses are based is no longer linear and might not be significant (Frutos et al., 2021).

1.4. The conspiracy theory of SARS-CoV-2: the voluntarily release from a laboratory

The other issue to be addressed beside the origin of SARS-CoV-2 is how this virus infected human beings at the first place. The marginal conspiracy theory of a voluntary released of an engineered virus forwarded by the press, blogs and politicians (Sutton, 2020; Everington, 2020) is not supported by any data (Calisher et al., 2020; Fowdy, 2020). This hypothesis of voluntary release has an impact on part of the population experiencing fear and distress, especially because there is still no clear explanation for the route of SARS-CoV-2 infection. There is consensus within the scientific community to consider that SARS-CoV-2 has not been engineered and is a naturally occurring virus. Therefore, it is simply impossible to voluntarily release an engineered virus which does not exist. There is thus no voluntary release (Calisher et al., 2020).

1.5. A laboratory accident

Another hypothesis is the accidental infection of laboratory staff working on naturally occurring Sarbecoviruses. Accidents happen and have already been reported during the SARS epidemic in Taiwan, Singapore and China (Webster, 2004; WHO, 2004). This is not limited to SARS-CoV (Heymann et al., 2004). When it happened in Beijing in 2004, the information was immediately released and an investigation involving both WHO and Chinese governmental agencies was conducted, patients were identified and treated (WHO, 2004). There is today no evidence that such an accident had happened with SARS-CoV-2.. Because of the incubation period of COVID-19, the weak symptoms, the significant rate of asymptomatic patients and the low virulence (with an estimated fatality rate of 3.26%, but more likely around 1% to 2% which is significantly lower than SARS-CoV with 9.6%), an accident could have easily remained unnoticed. But staff members of the Wuhan Institute of Virology have all been tested negative indicating that no accident occurred there (Cohen, 2020). One must remember that SARS-CoV-2 was never found in the wild and that RaTG13 does not exist as real virus but instead only as a sequence in a computer (Zhou et al., 2020a; Ge et al., 2016). It is a virtual virus which thus cannot leak from a laboratory. This hypothesis has been considered as “extremely unlikely” by the official WHO investigation team (Dyer, 2021). Therefore, although a laboratory accident can never be definitively excluded, there is currently no evidence to support it.

1.6. A contamination from rural and wild environments

A more likely hypothesis is a contamination in rural and wild environments. Owing to the designation of HSWM as the official epicenter and origin of the COVID-19 pandemic, the focus was put on cities and wet markets. However, the main risk of contact and viral contamination lies in anthropized rural environments and to a lower extent in the recreational human presence in wild environments. Coronaviruses are circulating in various animal species and thus contact with animals, respiratory droplets or feces, occurring preferentially in rural areas, represent the main route of human contamination. Land conversion in these areas generates mosaic landscapes attracting wild animals and bringing them to close contact with humans (Afelt et al., 2018; Reuter, 2016). Deforestation is aggravating this phenomenon (Afelt et al., 2018). The concentration and diversity of bat-borne viruses is higher in human rural settlements than in the wild (Afelt et al., 2018; Reuter, 2016). With a growing human population, a need for more converted land for agriculture and housing, and a fast-growing deforestation, the probability of seeing further emerging coronavirus-related infectious diseases is rising.

Frutos, R., Gavotte, L., & Devaux, C. A. (2021). Understanding the origin of COVID-19 requires to change the paradigm on zoonotic emergence from the spillover model to the viral circulation model. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases, 104812. Advance online publication. https://doi.org/10.1016/j.meegid.2021.104812