Crucial Mutations of Spike Protein on SARS-CoV-2 Evolved to Variant Strains Escaping Neutralization of Convalescent Plasmas and RBD-Specific Monoclonal Antibodies

Abstract

Small number of SARS-CoV-2 epidemic lineages did not efficiently exhibit a neutralization profile, while single amino acid mutation in the spike protein has not been confirmed in altering viral antigenicity resulting in immune escape. To identify crucial mutations in spike protein that escape humoral immune response, we evaluated the cross-neutralization of convalescent plasmas and RBD-specific monoclonal antibodies (mAbs) against various spike protein-based pseudoviruses. Three of 24 SARS-CoV-2 pseudoviruses containing different mutations in spike protein, including D614G, A475V, and E484Q, consistently showed an altered sensitivity to neutralization by convalescent plasmas. A475V and E484Q mutants are highly resistant to neutralization by mAb B38 and 2-4, suggesting that some crucial mutations in spike protein might evolve SARS-CoV-2 variants capable of escaping humoral immune response.

Computational Analysis of Molnupiravir

“…The receptor binding domain (RBD) is located on the head of S1 and binds the cellular receptor angiotensin-converting enzyme 2 (ACE2), initiating the membrane fusion of the virus and host cell. At this point, eight mutations (Y453F, L455F, F456L, A475V, A475S, T500S, N501Y, and Y505H) in the RBD and hACE2 interaction region (RBD/hACE2) were used to investigate the interaction mechanism of the reported tautomers of molnupiravir tautomers towards Spike protein, RBD as a target [39]. interesting finding can be highlighted for the interaction of the hydroxyl-oxime tautomer of molnupiravir with the spike protein, RBD.…”

Coronavirus Disease (COVID-19) Control between Drug Repurposing and Vaccination: A Comprehensive Overview

“…The SARS-CoV-2 acquires unique mutations on spike surface protein to improve the binding affinity to the cellular ACE-II receptors and to escape the neutralization of convalescent plasmas, vaccine-derived antibodies, and RDB-specific monoclonal antibodies. A recent study stated that the variants with the spike alterations D614G, A475V, and E484Q/K showed an altered sensitivity to neutralization by convalescent plasma [124]. The mutations R346S, L452R, and S477N, residing at the receptor-binding domain of the S protein, were associated with flexible interaction with the ACE2 receptor and, consequently, increased transmissibility of SARS-CoV-2 but less had affinity to neutralizing antibodies [125,126].…”

Bovine-derived antibodies and camelid-derived nanobodies as biotherapeutic weapons against SARS-CoV-2 and its variants: A review article

“…Therefore larger cases of breakthrough infection are being reported in vaccinated people getting infected with emerging variants, such as the recently emerged Omicron variant, thus posing a potential risk of infection and illness even after vaccination [ 6 , 7 , 9 , [30] , [31] , [32] , [33] ]. Likewise, monoclonal antibodies and convalescent sera, show less efficacy by inducing resistance to neutralization [ [34] , [35] , [36] , [37] , [38] , [39] , [40] ] even as new SARS-CoV-2 variants emerge (as shown in Table 2 ) . Antigenic diversity, limited effectiveness, tiny produced quantities, and short-term immune responses are the barriers that need addressing before vaccinations generally become available [ 41 , 42 ].…”