Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein (S) plays critical roles in host cell entry. Non-synonymous substitutions affecting S are not uncommon and have become fixed in a number of SARS-CoV-2 lineages. A subset of such mutations enable escape from neutralizing antibodies or are thought to enhance transmission through mechanisms such as increased affinity for the cell entry receptor, angiotensin-converting enzyme 2 (ACE2). Independent genomic surveillance programs based in New Mexico and Louisiana contemporaneously detected the rapid rise of numerous clade 20G (lineage B.1.2) infections carrying a Q677P substitution in S. The variant was first detected in the US on October 23, yet between 01 Dec 2020 and 19 Jan 2021 it rose to represent 27.8% and 11.3% of all SARS-CoV-2 genomes sequenced from Louisiana and New Mexico, respectively. Q677P cases have been detected predominantly in the south central and southwest United States; as of 03 Feb 2021, GISAID data show 499 viral sequences of this variant from the USA. Phylogenetic analyses revealed the independent evolution and spread of at least six distinct Q677H sub-lineages, with first collection dates ranging from mid-August to late November 2020. Four 677H clades from clade 20G (B.1.2), 20A (B.1.234), and 20B (B.1.1.220, and B.1.1.222) each contain roughly 100 or fewer sequenced cases, while a distinct pair of clade 20G clusters are represented by 754 and 298 cases, respectively. Although sampling bias and founder effects may have contributed to the rise of S:677 polymorphic variants, the proximity of this position to the polybasic cleavage site at the S1/S2 boundary are consistent with its potential functional relevance during cell entry, suggesting parallel evolution of a trait that may confer an advantage in spread or transmission. Taken together, our findings demonstrate simultaneous convergent evolution, thus providing an impetus to further evaluate S:677 polymorphisms for effects on proteolytic processing, cell tropism, and transmissibility.
Competing Interest Statement
The authors have declared no competing interest.
Funding Statement
This work was supported by a COVID-19 Fast Grants award from Emergent Ventures, an initiative of the Mercatus Center at George Mason University (J.P.K.), and by an intramural grant and other funding from the Office of the Vice Chancellor for Research at LSU Health Sciences Center Shreveport (J.P.K., R.S.S., J.A.V.); an Institutional Development Award from the National Institutes of General Medical Sciences of the NIH under grant number P20 GM121307 (C.G.K.); by the Swiss National Science Foundation through grant number 31CA30196046 (E.B.H.), by the U.S. National Center for Research Resources and the National Center for Advancing Translational Sciences of the National Institutes of Health through Grant Number UL1TR001449 (D.L.D., D.B.D), a KL2 Mentored Career Development Award KL2R001448 (D.B.D), and a Translational and Clinical Pilot Project Award CTSC008-11 (D.B.D). We would like to thank the UNM Center for Advanced Research Computing, supported in part by the National Science Foundation, for providing the high performance computing resources used in this work. The authors have not received payment or services from any third parties for any aspect of the submitted work, other than the grant funding explicitly listed above.
Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
Yes
The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
SARS-CoV-2 genome sequences were generated under IRB approved protocols STUDY00001445 (LSU Health Sciences Center), and 14-039 and 20-151 (University of New Mexico Health Sciences Center).
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Footnotes
↵† senior authors
Added a citation to a relevant biorxiv preprint. Fixed a few more typos. Added Q677H analysis to model in Figure 5. Corrected middle initial for one of the co-authors (Michael W Edwards).
Data Availability
All data for this manuscript is made available via websites and in publicly accessible databases. A time-stamped version of the Nextstrain build used in this manuscript can be found here: https://nextstrain.org/groups/neherlab/ncov/S.Q677/2020-02-04, and the most recently updated version of this build can be viewed here: https://nextstrain.org/groups/neherlab/ncov/S.Q677.
https://nextstrain.org/groups/neherlab/ncov/S.Q677/2020-02-04
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