The Proximal Origin of SARS-CoV-2

[arambaut]

This paper has now been published here: https://www.nature.com/articles/s41591-020-0820-9
The published version includes updates and corrections and should be considered the final version (it is also Open Access).

The Proximal Origin of SARS-CoV-2

Kristian G. Andersen^1,2*, Andrew Rambaut³, W. Ian Lipkin⁴, Edward C. Holmes⁵ & Robert F. Garry^6,7

¹Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.

²Scripps Research Translational Institute, La Jolla, CA 92037, USA.

³Institute of Evolutionary Biology, University of Edinburgh, Edinburgh, UK.

⁴Center for Infection and Immunity, Mailman School of Public Health of Columbia University, New York, New York, USA.

⁵Marie Bashir Institute for Infectious Diseases and Biosecurity, School of Life and Environmental Sciences and School of Medical Sciences, The University of Sydney, Sydney, Australia.

⁶Tulane University, School of Medicine, Department of Microbiology and Immunology, New Orleans, LA, USA.

⁷Zalgen Labs, LCC, Germantown, MD, USA.

^*Corresponding author:

Kristian G. Andersen
Department of Immunology and Microbiology,
The Scripps Research Institute,
La Jolla, CA 92037,
USA.

Since the first reports of a novel pneumonia (COVID-19) in Wuhan city, Hubei province, China there has been considerable discussion and uncertainty over the origin of the causative virus, SARS-CoV-2. Infections with SARS-CoV-2 are now widespread in China, with cases in every province. As of 14 February 2020, 64,473 such cases have been confirmed, with 1,384 deaths attributed to the virus. These official case numbers are likely an underestimate because of limited reporting of mild and asymptomatic cases, and the virus is clearly capable of efficient human-to-human transmission. Based on the possibility of spread to countries with weaker healthcare systems, the World Health Organization has declared the COVID-19 outbreak a Public Health Emergency of International Concern (PHEIC). There are currently neither vaccines nor specific treatments for this disease.

See here for full text: https://www.nature.com/articles/s41591-020-0820-9

[profbillg1901]

I concur with this analysis at the amino acid level. I would add, however, that even if two virus isolates have an IDENTICAL amino acid sequence, that would not automatically make one the origin of the other. In my post 10 days ago, Tackling Rumors of a Suspicious Origin of nCoV2019 , I showed that mutations in the 3rd wobble base in an otherwise conserved region accumulate as to make seemingly identical viruses very much separated in time – indeed over decades.

It is time to leave playing “who’s ur daddy” to daytime television. No known viral RNA sequence is the daddy of SARS-CoV-2. No match. If it doesn’t fit, you must acquit. It is all bat guano. Whatever analogy you like. A thrust of distrust and recrimination is not the path to protecting the planet from a viral catastrophe.

Bill Gallaher

[Kristian_Andersen]

Mandarin translation thanks to CHEN Guo from the Center for Infection and Immunity in the Columbia Mailman School of Public Health.

The Proximal Origin of SARS-CoV-2_ChineseSummary.pdf (198.5 KB)

[fuyutao]

@arambaut

For a precursor virus to acquire the polybasic cleavage site and mutations in the spike protein suitable for human ACE2 receptor binding, an animal host would likely have to have a high population density – to allow natural selection to proceed efficiently – and an ACE2 gene that is similar to the human orthologue.

There is one animal species meeting these 3 criteria:

1. The species is common with a high population density, some running in the wild;
2. BLASTing the short SARS-CoV-2 furin cleavage site PRRARS against coronavirus, there is only one species ranked above bat, and the hit is also in spike protein;
3. In a peer reviewed article (https://onlinelibrary.wiley.com/doi/10.1002/jmv.25726), the species’ key ACE2 amino acids are closer to human than between pangolin and human. Another paper in preprint (https://www.researchgate.net/publication/339741547_Predicting_the_Angiotensin_Converting_Enzyme_2_ACE2_Utilizing_Capability_as_the_Receptor_of_SARS-CoV-2) predicts the species’ ACE2 can bind SARS-CoV-2.

[xiaowei.jiang]

@arambaut

glycan

I noticed in the published version on Nature Med it has an extended discussion on the “glycan shield”. The analysis done in this correspondence only refers to one O-linked glycan motif. The “glycan shield” mostly refers to N-linked glycans, which are quite abundant in beta coronavirus and are the major constituents of the “glycan shield”. So there is a big jump in the discussion which may lead to confusion. I just post an initial analysis here in collaboration with David Robertson, and will post a full analysis on this later. 02_surface.pdf (170.9 KB) 02_surface_wuhan_ref_O_linked.pdf (121.3 KB)