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The omicron (B.1.1.529) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is responsible for coronavirus disease 2019 (Covid-19), has spread rapidly around the world and has already become the predominant variant circulating in many countries. As of February 2022, omicron variants have been divided into four distinct sublineages: BA.1, BA.1.1, BA.2, and BA.3.1 Most circulating omicron variants belong to sublineage BA.1; however, in Denmark, India, and the Philippines, the sublineage BA.2 is now becoming dominant.
As compared with the Wuhan/Hu-1/2019 reference strain, the sublineage BA.2 of the omicron variant has 16 amino acid substitutions in the receptor-binding domain of the spike (S) protein of SARS-CoV-2,2 which is the primary target for monoclonal antibody–based therapy. The BA.2 and BA.1 variants share 12 of these 16 substitutions; however, BA.2 has four substitutions in the receptor-binding domain (i.e., S371F, T376A, D405N, and R408S) that differ from those in BA.1. These findings suggest that there may be differences in the effectiveness of monoclonal antibodies against these different omicron sublineages. Accordingly, we examined the neutralizing ability of therapeutic monoclonal antibodies that have been approved by the Food and Drug Administration, individually and in combination, against the omicron BA.2 subvariant hCoV-19/Japan/UT-NCD1288-2N/2022 (omicron/BA.2; NCD1288), which was isolated from a traveler who arrived in Japan from India. Whole-genome sequencing analysis of the NCD1288 virus stock confirmed that it had the 16 substitutions that are characteristic of the omicron variant in the receptor-binding domain of the S protein, as compared with the Wuhan/Hu-1/2019 reference strain...
The susceptibilities of omicron/BA.2 (NCD1288) to remdesivir, molnupiravir, and nirmatrelvir were similar to those of the ancestral strain and other variants of concern (i.e., 50% inhibitory concentration values for these three agents that differed by factors of 2.5 to 4.5, 0.7 to 1.6, and 1.5 to 3.3, respectively) (Table 1).3 Clinical studies are warranted to determine whether these antiviral therapies are indeed effective against omicron/BA.2 infections. Our data indicate that some therapeutic monoclonal antibodies (REGN10987–REGN10933, COV2-2196–COV2-2130, and S309) have lower neutralizing activity against omicron/BA.2 than against earlier variant strains.
Published in NEJM (March 9, 2022):
