Abstract
Coronavirus research has gained tremendous attention because of the COVID-19 pandemic, caused by the novel severe acute respiratory syndrome coronavirus (nCoV or SARS-CoV-2). In this review, we highlight recent studies that provide atomic-resolution structural details important for the development of monoclonal antibodies (mAbs) that can be used therapeutically and prophylactically and for vaccines against SARS-CoV-2. Structural studies with SARS-CoV-2 neutralizing mAbs have revealed a diverse set of binding modes on the spike’s receptor-binding domain and N-terminal domain and highlight alternative targets on the spike. We consider this structural work together with mAb effects in vivo to suggest correlations between structure and clinical applications. We also place mAbs against severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses in the context of the SARS-CoV-2 spike to suggest features that may be desirable to design mAbs or vaccines capable of conferring broad protection.
Highlights
Coronavirus research has gained tremendous attention because of the COVID-19 pandemic, caused by the novel severe acute respiratory syndrome coronavirus
We describe recent insights into the structural conformation of the severe acute respiratory syndrome (SARS)-CoV-2 spike, as it relates to exposure of monoclonal antibodies (mAbs) epitopes
While the S receptor-binding motif (RBM) is an important target for SARS-CoV-2 neutralization because mAbs targeting this site compete with angiotensin-converting enzyme 2 (ACE2) binding, cross-neutralization with other coronaviruses is more likely to occur by mAbs that bind more conserved regions, such as the receptor-binding domain (RBD) core
Summary
Like the spikes of SARS-CoV and MERS-CoV, the SARS-CoV-2 spike, S, is a trimeric class I fusion protein and can be divided into the receptor-binding S1 and the membraneanchored S2 subunits (Figure 1A) [14,15,16]. The RBM of SARS-CoV-2 interacts with the host cell receptor, angiotensin-converting enzyme 2 (ACE2) (Figure 1B). Middle-Left: Side view of Side prefusion with 2 RBDsS in the 2down conformation (RBMs hidden) and one RBD in the up conformation (RBM exposed), bound to the ACE2 receptor. Right: Side view of postfusion SARS-CoV-2 S after a collapse allowing HR2 to form a six-helix bundle. Right: Side view of postfusion SARS-CoV-2 S after a collapse allowing HR2 to form a six-helix bundle with HR1, resulting with HR1, resulting in fusion of the viral membrane with the host cell membrane.
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