Efficacy of Antiviral Agents against Omicron Subvariants BQ.1.1 and XBB
Masaki Imai, Mutsumi Ito, Maki Kiso, Seiya Yamayoshi, Ryuta Uraki, Shuetsu Fukushi, Shinji Watanabe, Tadaki Suzuki, Ken Maeda, Yuko Sakai‐Tagawa, Kiyoko Iwatsuki‐Horimoto, Peter Halfmann, Yoshihiro Kawaoka
Abstract
Efficacy of Antiviral Agents against Omicron Subvariants BQ.1.1 and XBB To the Editor: Three sublineages of the B.1.1.529(omicron) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have serially transitioned into globally dominant formsfirst BA.1, then BA.2, and then BA.5.As of October 2022, most circulating omicron variants belong to BA.5.However, the prevalence of BQ.1.1 (a BA.5 subvariant) and XBB (a BA.2 subvariant) is increasing rapidly in several countries, including the United States and India.BA.2 and BA.5 variants have been shown to have less sensitivity to certain monoclonal antibodies than previously circulating variants of concern. 1-5Notably, as compared with BA.5 and BA.2, BQ.1.1 and XBB carry additional substitutions in the receptor-binding domain of the spike (S) protein, which is the major target for vaccines and therapeutic monoclonal antibodies for coronavirus disease 2019 (Covid-19).These subvariants may, therefore, be more immune-evasive than BA.5 and BA.2.We assessed the efficacy of therapeutic monoclonal antibodies against omicron BQ.1.1 (hCoV-19/ Japan/TY41-796/2022; TY41-796) and XBB (hCoV-19/Japan/TY41-795/2022; TY41-795), which were isolated from patients.The BQ.1.1 isolate had three more substitutions (R346T, K444T, and N460K) in its receptor-binding domain than a BA.5 (hCoV-19/Japan/TY41-702/2022) isolate (Fig. S1A in the Supplementary Appendix, available with the full text of this letter at NEJM.org).The XBB isolate had nine more changes (G339H, R346T, L368I, V445P, G446S, N460K, F486S, F490S, and the wild-type amino acid at position 493) in its receptor-binding domain than a BA.2 (hCoV-19/Japan/UT-NCD1288-2N/2022) isolate