The genetic structure of SARS‐CoV‐2 does not rule out a laboratory origin

Abstract

Severe acute respiratory syndrome‐coronavirus (SARS‐CoV)‐2′s origin is still controversial. Genomic analyses show SARS‐CoV‐2 likely to be chimeric, most of its sequence closest to bat CoV RaTG13, whereas its receptor binding domain (RBD) is almost identical to that of a pangolin CoV. Chimeric viruses can arise via natural recombination or human intervention. The furin cleavage site in the spike protein of SARS‐CoV‐2 confers to the virus the ability to cross species and tissue barriers, but was previously unseen in other SARS‐like CoVs. Might genetic manipulations have been performed in order to evaluate pangolins as possible intermediate hosts for bat‐derived CoVs that were originally unable to bind to human receptors? Both cleavage site and specific RBD could result from site‐directed mutagenesis, a procedure that does not leave a trace. Considering the devastating impact of SARS‐CoV‐2 and importance of preventing future pandemics, researchers have a responsibility to carry out a thorough analysis of all possible SARS‐CoV‐2 origins.

Tracing the origins of SARS-COV-2 in coronavirus phylogenies: a review

“…However, bioinformatic analyses revealed biases in codon usages that might reflect some genetic manipulation (Gu et al 2020). Segreto and Deigin develop the hypothesis of a genome modified by molecular engineering (Segreto and Deigin 2020). More thorough analyses are warranted to clarify this issue.…”

Retrouver les origines du SARS-CoV-2 dans les phylogénies de coronavirus

“…Zhou et al 2020a;Lam et al 2020;Xiao et al 2020;Andersen et al 2020). However, in the absence of evidence regarding the last animal intermediate before human contamination (the "proximal" origin of the virus), some authors suggested that SARS-CoV-2 may have been manufactured in a laboratory (synthetic origin) (Segreto et Deigin 2020) .…”

“…However, bioinformatic analyses revealed biases in codon usages that might reflect some genetic manipulation(Gu et al 2020). Segreto and Deigin develop the hypothesis of a genome modified by molecular engineering(Segreto et Deigin 2020). More thorough analyses are warranted to clarify this issue.15/26Beyond the frame of existing national regulations (e.g.…”

Urgent Need for Field Surveys of Coronaviruses in Southeast Asia to Understand the SARS-CoV-2 Phylogeny and Risk Assessment for Future Outbreaks

“…Additionally, there could be sequencing errors due to several factors such as poor sample quality, improper handling, secondary PCR enrichment, and low-quality measurements [16,18]. The RaTG13 strain was isolated in 2013, but its complete genomic sequence (GenBank ID MN996532) was submitted after the emergence of SARS-CoV-2 in 2020 [19]. Additionally, the RNA-dependent RNA polymerase (RdRp) gene of RaTG13 is identical to that of another bat CoV sequence BtCoV/4991 (GenBank ID KP876546) submitted in 2015 [19].…”

“…The RaTG13 strain was isolated in 2013, but its complete genomic sequence (GenBank ID MN996532) was submitted after the emergence of SARS-CoV-2 in 2020 [19]. Additionally, the RNA-dependent RNA polymerase (RdRp) gene of RaTG13 is identical to that of another bat CoV sequence BtCoV/4991 (GenBank ID KP876546) submitted in 2015 [19]. Strikingly, NCBI KRONA analysis of the RaTG13 sequence suggested the possibility of DNA contamination, and the sequence was considered a fossil record [7,20].…”