Cell Research, 19 July, 2024, DOI：https://doi.org/10.1093/nar/gkae740

Deletion of V483 in the spike confers evolutionary advantage on SARS-CoV-2 for human adaptation and host-range expansion after a prolonged pandemic

Can Yue, Shuo Liu, Bo Meng, Kaiyue Fan, Sijie Yang, Pan Liu, Qianhui Zhu, Xin Mao, Yuanling Yu, Fei Shao, Peng Wang, Youchun Wang, Ravindra Kumar Gupta, Yunlong Cao & Xiangxi Wang

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has undergone continuous evolution since its initial outbreak in 2019. The emergence of Omicron as the dominant variant occurred abruptly after 2022. A highly mutated Omicron variant, BA.2.86, has recently been identified and reported in multiple countries. The global prevalence of this variant is gradually increasing, as confirmed by the World Health Organization (WHO), which has categorized it as a variant under monitored (VUM). The Spike (S) protein of BA.2.86 has achieved more than 30 amino acid changes since its divergence from the parental BA.2 strain. Among these changes, the deletion of residue 483 (∆483) in the receptor binding domain (RBD) region stands out (Fig. 1a; Supplementary information, Fig. S1), as deletions in the S protein typically occur in the N-terminal domain (NTD) region of SARS-CoV-2 variants. Interestingly, the absence of residue 483 has been observed in SARS. Phylogenic and receptor usage analysis revealed that ∆483 is widespread among sarbecoviruses and is not linked to ACE2 binding (Fig. 1b). Moreover, the deletion is genetically stable and can be sustained. These findings imply that ∆483 does not hinder the interaction of the virus with ACE2. In fact, it sometimes confers advantage since strains harboring the mutation become new prevalent strains. To assess the impact of the sudden deletion of 483 in SARS-CoV-2 and its potential link to the viral adaptation across different hosts, as well as its role in human pandemic, we conducted a multidimensional analysis covering receptor usage and infection capabilities in different hosts, along with the effects of the deletion on cell–cell fusion, S protein cleavage, and immunogenicity. The findings reported here aid in the understanding of the evolutionary dynamics of the virus.

Article link：https://www.nature.com/articles/s41422-024-01000-8