Neutralizing antibodies against SARS-CoV-2: current understanding, challenge and perspective

Abstract

The rapid emergence of Coronavirus disease-2019 (COVID-19) caused by severe acute respiratory syndrome 2 coronavirus (SARS-CoV-2) as a pandemic that presents an urgent human health crisis. Many SARS-CoV-2 neutralizing antibodies (NAbs) were developed with efficient therapeutic potential. NAbs-based therapeutics against SARS-CoV-2 are being expedited to preclinical and clinical studies with two antibody drugs, LY3819253 (LY-CoV555) and REGN-COV2 (REGN10933 and REGN10987), approved by the US Food and Drug Administration for emergency use authorization for treating COVID-19. In this review, we provide a systemic overview of SARS-CoV-2 specific or cross-reactive NAbs and discuss their structures, functions and neutralization mechanisms. We provide insight into how these NAbs specific recognize the spike protein of SARS-CoV-2 or cross-react to other CoVs. We also summarize the challenges of NAbs therapeutics such as antibody-dependent enhancement and viral escape mutations. Such evidence is urgently needed to the development of antibody therapeutic interventions that are likely required to reduce the global burden of COVID-19.

Virus neutralizing antibody responses after two doses of BBIBP-CorV (Sinopharm, Beijing CNBG) vaccine

“…Quantification of neutralizing antibody levels is clearly essential for vaccine development and for assessing protective immunity both at the individual and community levels. In addition, RBD binding virus neutralizing antibodies are most promising therapeutic tools for preventing or curing the COVID-19 disease 33,34 .…”

Factors Affecting the Antibody Immunogenicity of Vaccines against SARS-CoV-2: A Focused Review

“…Thus far, the D614G mutation of SARS-CoV-2 S protein is considered to be the main mutation detected, which may lead to an increase in infectivity and mortality [ 48 , 49 ]. Although the potency of RBD-targeting nAbs against the D614G variant was not reduced, and antibodies stimulated by natural infection with SARS-CoV-2 containing D614 or G614 can be cross-neutralized, the conformational transfer induced by D614G towards ACE2 binding active states may still affect the effectiveness of some nAbs (e.g., type III nAbs that only bind closed RBDs) [ 50 ]. On the other hand, the virus with any of the mutations on E484, F490, Q493, and S494 of the S protein shows complete or partial resistance to the potent nAbs (C121 and C144) [ 51 ].…”

Molecular rationale for SARS-CoV-2 spike circulating mutations able to escape bamlanivimab and etesevimab monoclonal antibodies

“…The ability of SARS-CoV-2 mAbs to select any of these variants that is apparently fit and that naturally occurs even at low frequencies in circulating viral populations suggests that the therapeutic use of single mAb might select for escape mutants, although the extent to which resistance will impact the effectiveness of Abs in SARS-CoV-2 therapeutic and vaccine settings is still a matter of intense investigation 10 , 18 , 53 , 54 . In this arena, the purpose of this work is to provide an atomistic-based, in silico perspective of the role eventually played by currently circulating S-RBD CoV‑2 mutations in escaping binding of the two mAbs bamlanivimab and etesevimab as a proof of concept.…”