The effects of amino acid substitution of spike protein and genomic recombination on the evolution of SARS-CoV-2

Abstract

Over three years’ pandemic of 2019 novel coronavirus disease (COVID-19), multiple variants and novel subvariants have emerged successively, outcompeted earlier variants and become predominant. The sequential emergence of variants reflects the evolutionary process of mutation-selection-adaption of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Amino acid substitution/insertion/deletion in the spike protein causes altered viral antigenicity, transmissibility, and pathogenicity of SARS-CoV-2. Early in the pandemic, D614G mutation conferred virus with advantages over previous variants and increased transmissibility, and it also laid a conservative background for subsequent substantial mutations. The role of genomic recombination in the evolution of SARS-CoV-2 raised increasing concern with the occurrence of novel recombinants such as Deltacron, XBB.1.5, XBB.1.9.1, and XBB.1.16 in the late phase of pandemic. Co-circulation of different variants and co-infection in immunocompromised patients accelerate the emergence of recombinants. Surveillance for SARS-CoV-2 genomic variations, particularly spike protein mutation and recombination, is essential to identify ongoing changes in the viral genome and antigenic epitopes and thus leads to the development of new vaccine strategies and interventions.

Genomic Surveillance for SARS-CoV-2 Variants: Dominance of XBB Replacement — China, January–June 2023

“…In the first half of 2023, XBB.1.5, XBB.1.9.1, and XBB.1.16 were identified as the prevailing subvariants of XBB in China, showing no significant variance in replacement rates. Relative to XBB.1.16, a notable resemblance in spike protein sequences was observed between XBB.1.5 and XBB.1.9 (12)(13). Nonetheless, the antigenic distinctions among XBB subvariants were notably lower compared to the previously predominant strains BA.5.2 and BF.7.…”

Identification of an IGHV3-53-Encoded RBD-Targeting Cross-Neutralizing Antibody from an Early COVID-19 Convalescent

“…Omicron and its sublineages underwent a significant shift compared with the wild strain [ 38 ], often displaying enhanced transmissibility, and reduced vaccine effectiveness and antibody neutralizing activity, as well as increased likelihood of reinfection [ 39 ]. Especially, the occurrence of recombination when different variants are co-infected, such as XBB, which is a recombinant strain of BA.2.10.1 and BA.2.75 [ 40 ], allows the virus to acquire a broader phenotype and have more opportunities to escape immune stress [ 41 ].…”

Virological and Mitochondriopathogical Characteristics of the SARS-CoV-2 Omicron XBB.1.16 Spike

“…8 Studies have shown that XBB.1.16 has a significant transmission advantage over its predecessors, although it does not lead to a significant increase in disease severity. 9 Given its unique S profile, it is reasonable to infer that the virological features of XBB.1.16 differ substantially from those of other variants. However, the virological characteristics of XBB.1.16 are still not well understood.…”

“…XBB.1.16, when compared with the ancestral SARS-Cov-2, exhibits 22 mutations in the receptor-binding domain (RBD), which are likely to be responsible for its increased transmissibility and ability to evade antibodies . Studies have shown that XBB.1.16 has a significant transmission advantage over its predecessors, although it does not lead to a significant increase in disease severity . Given its unique S profile, it is reasonable to infer that the virological features of XBB.1.16 differ substantially from those of other variants.…”