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On November 24, 2021, South Africa reported the identification of a new SARS-CoV-2 variant, B.1.1.529, to the World Health Organization (WHO). On November 26, 2021, the WHO designated B.1.1.529 as a variant of concern (VOC) named Omicron. This new variant features a number of concerning spike protein mutations. As illustrated below, these key mutations, also found in earlier variants, are present at or near sites regulating virus infectivity. In addition, Omicron displays a surprising number of new mutations. Of special interest are mutations occurring in the RBD and S1/S2 domain. The RBD is important for binding to cells, and the S1/S2 is important for processing the virus to enable entry into the cells.