Distinctive Features of the XBB.1.5 and XBB.1.16 Spike Protein Receptor-Binding Domains and Their Roles in Conformational Changes and Angiotensin-Converting Enzyme 2 Binding

Abstract

The emergence and the high transmissibility of the XBB.1.5 and XBB.1.16 subvariants of the SARS-CoV-2 omicron has reignited concerns over the potential impact on vaccine efficacy for these and future variants. We investigated the roles of the XBB.1.5 and XBB.1.16 mutations on the structure of the spike protein’s receptor-binding domain (RBD) and its interactions with the host cell receptor ACE2. To bind to ACE2, the RBD must transition from the closed-form to the open-form configuration. We found that the XBB variants have less stable closed-form structures that may make the transition to the open-form easier. We found that the mutations enhance the RBD–ACE2 interactions in XBB.1.16 compared to XBB.1.5. We observed significant structural changes in the loop and motif regions of the RBD, altering well-known antibody-binding sites and potentially rendering primary RBD-specific antibodies ineffective. Our findings elucidate how subtle structural changes and interactions contribute to the subvariants’ fitness over their predecessors.

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

“…The impact of the indicated common mutations was reported in previous studies. For example, K417N, Q498R, and N501Y were reported to enhance the ability of variants to bind with the ACE2 receptor . The unique mutations in XBB.1.16 bring new features to further change the virological characteristics of XBB.1.16.…”

“…For example, K417N, Q498R, and N501Y were reported to enhance the ability of variants to bind with the ACE2 receptor. 31 The unique mutations in XBB.1.16 bring new features to further change the virological characteristics of XBB.1.16. For example, E180V increases the infectivity of XBB.1.16 while S486P enhances the binding affinity to ACE2, thus providing XBB.1.16 the ability to evade the immune system.…”

Biomimetic nanomaterials for pulmonary infections: A prospective view in drug delivery systems

“…The structural moiety of SARS-CoV-2 keep changing and the variants of interest keeps evolving such as XBB.1.5, XBB.1.16 and EG.5. This remain the most challenging among healthcare units in developing drugs or vaccines sensitivity towards the variants (Sharma et al 2023). The side effects of acute respiratory distress syndrome (ARDS) in COVID-19 patients lead to associated complications in cardiovascular regions such as arrhythmias.…”

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

“…XBB, acknowledged as the first recombinant variant to reach global dominance, arises from recombination of the Omicron subvariants BJ.1 and BM.1.1.1, which are both part of BA.2.75 (6). This variant is notorious for its enhanced ability to evade immunity from both past infections and vaccinations, which played a significant role in its rapid spread and global prevalence (7). Nevertheless, the variation in the pace at which XBB has replaced other variants across different regions remains inadequately explained.…”