Efficacy of Antiviral Agents against the Omicron Subvariant BA.2.75
Emi Takashita, Seiya Yamayoshi, Shuetsu Fukushi, Tadaki Suzuki, Ken Maeda, Yuko Sakai‐Tagawa, Mutsumi Ito, Ryuta Uraki, Peter Halfmann, Shinji Watanabe, Makoto Takeda, Hideki Hasegawa, Masaki Imai, Yoshihiro Kawaoka
Abstract
Efficacy of Antiviral Agents against the Omicron Subvariant BA.2.75To the Editor: Five sublineages of the B.1.1.529(omicron) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) -BA.1, BA.2, BA.3, BA.4, and BA.5 -are recognized, and BA.5 is currently the predominant variant circulating globally. 1In India and Nepal, however, the prevalence of a subvariant of BA.2 (designated BA.2.75) is increasing rapidly and is now becoming dominant in Nepal. 2 Moreover, BA.2.75 has been detected in at least 25 other countries, including the United States, Singapore, Canada, the United Kingdom, Japan, and Australia; as such, it has spread across multiple continents. 2-4The World Health Organization designated BA.2.75 as a "variant of concern lineage under monitoring."Of additional concern, BA.2.75 may differ antigenically from BA.2.The receptor-binding domain of the spike (S) protein of SARS-CoV-2 is capable of inducing neutralizing antibodies and is the major target for monoclonal antibodybased therapy.BA.2, as compared with the reference strain Wuhan/Hu-1/2019, possesses 16 amino acid substitutions in the receptor-binding domain; BA.2 and BA.2.75 share 14 of these 16 substitutions.However, BA.2.75 possesses 4 amino acid changes in the receptor-binding domain (i.e., G339H, G446S, N460K, and the wild-type amino acid at position 493) that differ from those in BA.2, which suggests that the monoclonal antibodies authorized for emergency use by the Food and Drug Administration (FDA) may be less effective against BA.2.75 than against other SARS-CoV-2 strains and variants.To assess the efficacy of authorized therapeutic monoclonal antibodies against BA.2.75, we examined their neutralizing abilities against the BA.2.75 variant hCoV-19/Japan/TY41-716/2022 (TY41-716), which was isolated from a person traveling from India to Japan.Whole-genome sequencing of TY41-716 revealed that it possesses nine amino acid changes (K147E, W152R, F157L, I210V, G257S, D339H, G446S, N460K, and Q493