A new variant has been detected in a Kentucky nursing home, infecting 45 residents and health care personnel. Many of these infections arose in fully vaccinated individuals. The variant, which originated in Japan, has over 10,000 entries in the GISAID SARS-CoV-2 database. The variant contains five mutations previously noted in variants of concern or interest, two of which are in the Spike protein (Figure 1). It also contains many unique mutations. Here we describe the potential effects of each mutation on replication, immune evasion, and pathogenesis.

The R.1 variant shares a common origin with all variants of interest or concern. They are marked by what I call the Triad, three mutations, one the 5’ untranslated region: C241U, a second in the viral polymerase NSP12: P323L, and the third D614G in the exterior S1 domain of the spike protein. The D614G mutation increases the infectivity. The contribution of the other two members of the Triad remains a mystery. Together these three mutations characterize the first major variant first observed in early 2020. That virus soon displaced almost all of the original Wuhan isolates. The Triad virus is the parent of all variants of concern or, interest including Alpha, Beta, Gamma, Delta, Lambda, and Mu. Only two currently circulating variants, A.30 and A.23.1, both of East Africa origin, lack the Triad and are most likely independent descendants of the original Wuhan virus.