L18F substrain of SARS-CoV-2 VOC-202012/01 is rapidly spreading in England

The Variant of Concern (VOC)-202012/01 (also known as B.1.1.7) is a rapidly growing lineage of SARS-CoV-2. In January 2021, VOC-202012/01 constituted about 80% of SARS-CoV-2 genomes sequenced in England and was present in 27 out of 29 countries that reported at least 50 viral genomes. As this strain will likely spread globally towards fixation, it is important to monitor its molecular evolution. Based on GISAID data we systematically estimated growth rates of mutations acquired by the VOC lineage to find that L18F substitution in viral spike protein has initiated a substrain characterized by replicative advantage of 1.70 [95% CI: 1.56–1.96] in relation to the remaining VOC-202012/01 substrains. The L18F mutation is of significance because when recently analyzed in the context of the South African strain 501Y.V2 it has been found to compromise binding of neutralizing antibodies. We additionally indicate three mutations that were acquired by VOC-202012/01 in the receptor binding motif of spike, specifically E484K, F490S, and S494P, that may also give rise to escape mutants. Such mutants may hinder efficiency of existing vaccines and expand in response to the increasing after-infection or vaccine-induced seroprevalence.