In a new work, researchers analyze the virological properties of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron XBB subvariant, XBB.1.16 through thorough multiscale investigations.The SARS-CoV-2 XBB.1.16 variant has an effective reproductive number (Re) that is 1.27 and 1.17 times higher than that of the XBB.1 and XBB.1.5 subvariants, respectively, demonstrating the ability of this unique Omicron variant to spread swiftly.

The World Health Organization (WHO) started keeping an eye on XBB.1.16 on March 30, 2023, after it was discovered in various nations, including India, as a result of its heightened transmissibility. Earlier, the F486P alteration in the spike (S) protein of the SARS-CoV-2 Omicron XBB subvariants, including XBB.1.5 and XBB.1.9, were widely disseminated around the world.

The recent investigations revealed that XBB.1.16 had two S substitutions, E180V and T478R in the N-terminal domain (NTD) and receptor-binding domain (RBD), respectively, as compared to its forerunner mutant strains. Additionally, the XBB.1.16 RBD’s dissociation constant (KD) for the host receptor angiotensin-converting enzyme 2 (ACE2) was 2.4 times larger than that of XBB.1.5, but its KD values were noticeably lower than those of XBB.1, showing the binding affinities of this unique subvariant.

Pseudovirus experiments revealed that XBB.1.16’s infectivity was similar to that of XBB.1, but different from XBB.1.5, which had a higher infectivity than the parental XBB.1 mutant. It should be noted that this viral variant’s ability to infect hosts is significantly impacted by the substitution mutations S: T478R and S: E180V. While the T478R mutation increases the infectivity of XBB.1.16, the S: E180V substitution significantly reduced its viral infectivity.

XBB.1.16 likely acquired these two S protein mutations simultaneously as a strategy to evolve. This behavior has been previously observed in other Omicron subvariants, including BA.5 and XBB.1. Indeed, XBB.1.16 follows the evolutionary path of Omicron subvariants that emerged earlier.