Ten emerging SARS-CoV-2 spike variants exhibit variable infectivity, animal tropism, and antibody neutralization

Abstract

Emerging mutations in SARS-CoV-2 cause several waves of COVID-19 pandemic. Here we investigate the infectivity and antigenicity of ten emerging SARS-CoV-2 variants—B.1.1.298, B.1.1.7(Alpha), B.1.351(Beta), P.1(Gamma), P.2(Zeta), B.1.429(Epsilon), B.1.525(Eta), B.1.526-1(Iota), B.1.526-2(Iota), B.1.1.318—and seven corresponding single amino acid mutations in the receptor-binding domain using SARS-CoV-2 pseudovirus. The results indicate that the pseudovirus of most of the SARS-CoV-2 variants (except B.1.1.298) display slightly increased infectivity in human and monkey cell lines, especially B.1.351, B.1.525 and B.1.526 in Calu-3 cells. The K417N/T, N501Y, or E484K-carrying variants exhibit significantly increased abilities to infect mouse ACE2-overexpressing cells. The activities of furin, TMPRSS2, and cathepsin L are increased against most of the variants. RBD amino acid mutations comprising K417T/N, L452R, Y453F, S477N, E484K, and N501Y cause significant immune escape from 11 of 13 monoclonal antibodies. However, the resistance to neutralization by convalescent serum or vaccines elicited serum is mainly caused by the E484K mutation. The convalescent serum from B.1.1.7- and B.1.351-infected patients neutralized the variants themselves better than other SARS-CoV-2 variants. Our study provides insights regarding therapeutic antibodies and vaccines, and highlights the importance of E484K mutation.

Molecular Insights into the Differential Dynamics of SARS-CoV-2 Variants of Concern (VOC)

“…We also checked for the difference in the H-bond interactions among the residues calculated over the last 10ns of the trajectory. Results show that most of the H-bond interactions reported in earlier studies [46,47] were conserved in WT. ACE2 residue Y83 interacts with N487 of RBD across all the systems.…”

“…Results show that most of the H-bond interactions reported in earlier studies 44,45 were conserved in WT. ACE2 residue Tyr83 interacts with Asn487 of RBD across all the systems.…”

The significant immune escape of pseudotyped SARS-CoV-2 variant Omicron

“…The novel pseudotyped virus expressing Spike of Omicron (PV-Omicron) containing all of 32 mutations was constructed ( Figure 1 A). In addition, pseudotyped viruses expressing S proteins from the other current VOCs (Alpha, Beta, Gamma, and Delta) and VOIs (lambda, mu) constructed as previously were tested and reported [ 6 , 7 ]. To examine how much the neutralization sensitivity of Omicron variant is changed compared to the other SARS-CoV-2 variants, the PV-Omicron was tested against a panel of human sera from the convalescent COVID-19 patients who had infected with the original Strain ( Figure 1 B–I).…”

Myeloid cell-driven nonregenerative pulmonary scarring is conserved in multiple nonhuman primate species regardless of SARS-CoV-2 infection modality

“…SARS-CoV-2 infection continue to result in morbidity and mortality in large segments of the population, with some long-term sequelae persisting well beyond viral clearance in those that carry risk factors associated with severe clinical outcome 1, [37][38][39][40][41] . Variants of concern (VOC) are arising that threaten to continue the pandemic into the future to an uncertain degree, necessitating efforts that transcend vaccination strategies alone, and promote alternative prophylactic and therapeutic development both in acute and longerterm time frames post-infection [42][43][44][45][46] . Multifocal medical countermeasure development while this virus evolves to the human host necessitates a suitable animal model of infection that recapitulates the immunologic and clinically relevant aspects of COVID-19.…”