PT - JOURNAL ARTICLE AU - Yamasoba, Daichi AU - Uriu, Keiya AU - Plianchaisuk, Arnon AU - Kosugi, Yusuke AU - Pan, Lin AU - Zahradnik, Jiri AU - The Genotype to Phenotype Japan (G2P-Japan) Consortium AU - Ito, Jumpei AU - Sato, Kei TI - Virological characteristics of the SARS-CoV-2 Omicron XBB.1.16 variant AID - 10.1101/2023.04.06.535883 DP - 2023 Jan 01 TA - bioRxiv PG - 2023.04.06.535883 4099 - http://biorxiv.org/content/early/2023/04/09/2023.04.06.535883.short 4100 - http://biorxiv.org/content/early/2023/04/09/2023.04.06.535883.full AB - At the end of March 2023, XBB.1.16, a SARS-CoV-2 omicron XBB subvariant, emerged and was detected in various countries. Compared to XBB.1.5, XBB.1.16 has two substitutions in the S protein: E180V is in the N-terminal domain, and T478R in the receptor-binding domain (RBD). We first show that XBB.1.16 had an effective reproductive number (Re) that was 1.27- and 1.17-fold higher than the parental XBB.1 and XBB.1.5, respectively, suggesting that XBB.1.16 will spread worldwide in the near future. In fact, the WHO classified XBB.1.16 as a variant under monitoring on March 30, 2023. Neutralization assays demonstrated the robust resistance of XBB.1.16 to breakthrough infection sera of BA.2 (18-fold versus B.1.1) and BA.5 (37-fold versus B.1.1). We then used six clinically-available monoclonal antibodies and showed that only sotrovimab exhibits antiviral activity against XBB subvariants, including XBB.1.16. Our results suggest that, similar to XBB.1 and XBB.1.5, XBB.1.16 is robustly resistant to a variety of anti-SARS-CoV-2 antibodies. Our multiscale investigations suggest that XBB.1.16 that XBB.1.16 has a greater growth advantage in the human population compared to XBB.1 and XBB.1.5, while the ability of XBB.1.16 to exhibit profound immune evasion is comparable to XBB.1 and XBB.1.5. The increased fitness of XBB.1.16 may be due to (1) different antigenicity than XBB.1.5; and/or (2) the mutations in the non-S viral protein(s) that may contribute to increased viral growth efficiency.Competing Interest StatementThe authors have declared no competing interest.