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The proximal origin of SARS-CoV-2

Our take —

Using available genomes for SARS-CoV-2 and related coronaviruses from humans, bats, and pangolin, the study assesses the unique features of the novel virus and concludes that the features are likely of natural origin and not the result of laboratory manipulation. Whether these features evolved within an animal reservoir or in humans following initial spillover cannot be decided on genomes alone and will need confirmation from additional sampling.

Study design

Ecological, Modeling/Simulation, Other

Study population and setting

Strictly an analysis of existing SARS-related coronavirus genomes: SARS-CoV-2 genome from humans, RaTG13 SARS-related CoV from a bat, SARS-related CoV from a pangolin, SARS-CoV from humans, and two other SARS-related CoVs from bats.

Summary of Main Findings

The genome of SARS-CoV-2 has two unique features that distinguish it from other SARS-related coronaviruses: 1) a set of key changes in the amino acids within the region of the spike protein that the virus uses to bind and enter human cells and 2) a unique insertion of amino acids between the two subunits of the spike protein. The presence of similar spike protein changes in bat and pangolin coronaviruses and analogous amino acid insertions in MERS coronavirus and avian influenza viruses suggest that SARS-CoV-2 is of natural origin.

Study Strengths

Frames the hypotheses regarding the origin of the SARS-CoV-2 and evaluates the parsimony of each hypothesis against the available evidence.

Limitations

There is no way to conclusively discern based on genomic data alone whether unique features of SARS-CoV-2 occurred in animal reservoirs prior to spillover or during an initial human-to-human transmission phase prior to the recognized outbreak of cases. Additional genetic sequencing of coronaviruses in wildlife and serological surveys of SARS-CoV-2 in human populations will be necessary.

Value added

The paper dismisses speculation that SARS-CoV-2 was an engineered virus. The paper also provides testable hypotheses about whether the genomic features were acquired within animal reservoirs prior to spillover into humans or within humans during initial human-to-human transmission of a low-pathogenic zoonotic infection prior to the recognition of the outbreak.