Novel variant 501Y.V2 with triple spike receptor binding site substitutions

By 21 December, 301 new virus genomes collected in South Africa since November 1 were submitted to GISAID, bringing the total number of virus genome submissions from South Africa to 2,730. The 301 recent virus genomes include 182 from clade GH; 71 from clade GR; 45 from clade G; one from clade GV; and two from other clades. Of the 182 genomes from clade GH, 89% have three mutations in the spike receptor binding site (K417N, E484K, and N501Y). 27% of the 182 have a nine-nucleotide deletion in NSP6 in addition to the three mutations. Spike mutation N501Y is also found in the novel UK variant under investigation, which is from a different clade.

It has been reported, based on high-throughput experiments, that all three spike receptor binding site mutations (K417N, E484K and N501Y) were shown to mildly increase receptor binding. Because receptor binding interfaces are also common epitopes, receptor binding interface mutations could also affect binding of some antibodies to the virus and, in rare cases, have the potential to affect vaccine response. A triple mutant at the interface has not been observed yet in larger outbreaks and should be investigated in detail. Experimental data would be welcome to clarify the impact of the mutations.