Cooccurrence of N501Y, P681R and other key mutations in SARS-CoV-2 Spike

ABSTRACT

Analysis of circa 4.2 million severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome sequences on Global Initiative on Sharing All Influenza Data (GISAID) shows the spike mutations N501Y (common to Alpha, Beta, Gamma, Omicron variants) and P681R (central to Delta variants spread) have cooccurred 3,678 times between 17 October 2020 and 1 November 2021. In contrast, the N501Y+P681H combination is present in Alpha and Omicron variants and circa 1.1 million entries. Two-thirds of the 3,678 cooccurrences were in France, Turkey or US (East Coast), and the rest across 62 other countries. 55.5% and 4.6% of the cooccurrences were Alphas Q.4 and Gammas P.1.8 sub-lineages acquiring P681R; 10.7% and 3.8% were Deltas B.1.617.2 lineage and AY.33 sub-lineage acquiring N501Y; remaining 10.2% were in other variants. Despite the selective advantages individually conferred by N501Y and P681R, the N501Y+P681R combination counterintuitively didnt outcompete other variants in every instance. Although a relief to worldwide public health efforts, in vitro and in vivo studies are urgently required in the absence of a strong in silico explanation for this phenomenon. This study demonstrates a pipeline to analyse combinations of key mutations from public domain information in a systematic manner and provide early warnings of spread.