Structural Basis of SARS-CoV-2 and SARS-CoV Antibody Interactions

The 2019 coronavirus pandemic remains a major public health concern. Neutralizing antibodies (nAbs) represent a cutting-edge antiviral strategy. We focus here on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and SARS-CoV, and discuss current progress in antibody research against rampant SARS-CoV-2 infections. We provide a perspective on the mechanisms of SARS-CoV-2-derived nAbs, comparing these with existing SARS-CoV-derived antibodies. We offer insight into how these antibodies cross-react and cross-neutralize by analyzing available structures of spike (S) glycoprotein–antibody complexes. We also propose ways of adopting antibody-based strategies – such as cocktail antibody therapeutics against SARS-CoV-2 – to overcome the possible resistance of currently identified mutants and mitigate possible antibody-dependent enhancement (ADE) pathologies. This review provides a platform for the progression of antibody and vaccine design against SARS-CoV-2, and possibly against future coronavirus pandemics. Newly isolated SARS-CoV-2-derived mAbs [RBM-, N-terminal domain (NTD)-, and S2 subunit-targeting mAbs] have shown neutralizing effects and protection efficacy against SARS-CoV-2 in in vitro assays, animal models, and human clinical trials.Cross-reactivity and cross-neutralization of SARS-CoV-2-derived and SARS-CoV-derived mAbs may be largely influenced by the S glycoprotein domain that is targeted.The S1B core domain-targeting mAbs of both SARS-CoV and SARS-CoV-2 might exhibit better cross-reactivity and cross-neutralization compared with receptor-binding motif (RBM)-targeting mAbs. However, RBM-targeting mAbs might exhibit better neutralizing effects, although these effects might be virus-specific.The current Asp614Gly and other mutations in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S glycoprotein may increase infectivity and reduce monoclonal antibody (mAb) sensitivity. An ideal therapeutic strategy against escape mutants might lie in applying cocktail mAbs such as REGN-COV.