The receptor-binding domain (RBD) is a highly variable region in SARS-CoV-2 spike (S) protein. SARS-CoV-2 S protein N439K is a second most common mutation in the RBD through the end of 2020, which was first isolated in March 2020 in Scotland, on the background of D614G mutation. The N439K mutation enhances the binding of S protein to viral receptor hACE2 by creating a new salt bridge between these two proteins. The N439K mutant virus shows similar replication phenotype in culture cells, and similar clinical outcome with those of N439 wild type virus. This N439K mutation confers resistance against several neutralizing antibodies including FDA-approved monoclonal antibody as well as polyclonal sera from persons recovered from COVID-19.
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