Rapid and parallel adaptive mutations in spike S1 drive clade success in SARS-CoV-2.

The SARS-CoV-2 pandemic has resulted in numerous virus variants, some of which have altered receptor-binding or antigenic phenotypes. Here, we quantify the degree to which adaptive evolution is driving the accumulation of mutations across the genome. We correlate clade growth with mutation accumulation, compare rates of nonsynonymous to synonymous divergence, assess temporal clustering of mutations, and evaluate the evolutionary success of individual mutations. We find that spike S1 is the focus of adaptive evolution but also identify positively selected mutations in other proteins (notably Nsp6) that are sculpting the evolutionary trajectory of SARS-CoV-2. Adaptive changes in S1 accumulated rapidly, resulting in a remarkably high ratio of nonsynonymous to synonymous divergence that is 2.5× greater than that observed in influenza hemagglutinin HA1 at the beginning of the 2009 H1N1 pandemic. These findings uncover a high degree of adaptation in S1 and suggest that SARS-CoV-2 might undergo antigenic drift.

Rapid and parallel adaptive mutations in spike S1 drive clade success in SARS-CoV-2

The SARS-CoV-2 pandemic has resulted in numerous virus variants, some of which have altered receptor-binding or antigenic phenotypes. Here, we quantify the degree to which adaptive evolution is driving the accumulation of mutations across the genome. We correlate clade growth with mutation accumulation, compare rates of nonsynonymous to synonymous divergence, assess temporal clustering of mutations and evaluate the evolutionary success of individual mutations. We find that spike S1 is the focus of adaptive evolution, but also identify positively-selected mutations in other genes (notably Nsp6) that are sculpting the evolutionary trajectory of SARS-CoV-2. Adaptive changes in S1 accumulated rapidly, resulting in a remarkably high ratio of nonsynonymous to synonymous divergence that is 2.5X greater than that observed in influenza hemagglutinin HA1 at the beginning of the 2009 H1N1 pandemic. These findings uncover a high degree of adaptation in S1 and suggest that SARS-CoV-2 may undergo antigenic drift. Graphical

Complete Mapping of Mutations to the SARS-CoV-2 Spike Receptor-Binding Domain that Escape Antibody Recognition.

Antibodies targeting the SARS-CoV-2 spike receptor-binding domain (RBD) are being developed as therapeutics and are a major contributor to neutralizing antibody responses elicited by infection. Here, we describe a deep mutational scanning method to map how all amino-acid mutations in the RBD affect antibody binding and apply this method to 10 human monoclonal antibodies. The escape mutations cluster on several surfaces of the RBD that broadly correspond to structurally defined antibody epitopes. However, even antibodies targeting the same surface often have distinct escape mutations. The complete escape maps predict which mutations are selected during viral growth in the presence of single antibodies. They further enable the design of escape-resistant antibody cocktails-including cocktails of antibodies that compete for binding to the same RBD surface but have different escape mutations. Therefore, complete escape-mutation maps enable rational design of antibody therapeutics and assessment of the antigenic consequences of viral evolution.

Cryptic transmission of SARS-CoV-2 in Washington state.

After its emergence in Wuhan, China, in late November or early December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus rapidly spread globally. Genome sequencing of SARS-CoV-2 allows the reconstruction of its transmission history, although this is contingent on sampling. We analyzed 453 SARS-CoV-2 genomes collected between 20 February and 15 March 2020 from infected patients in Washington state in the United States. We find that most SARS-CoV-2 infections sampled during this time derive from a single introduction in late January or early February 2020, which subsequently spread locally before active community surveillance was implemented.