#Rbd cd collection series

(D) Graphical presentation of the frequency of RBD variant occurrences in the GISAID (left axis, colored bars), relative to buried surface area (BSA, right axis) presented as black bars. (C) RBD ACE2 binding surface, rotated 180 degrees relative to (B), that highlights residues adjacent to the ACE2 binding site, that exhibit amino acid variation of at least 0.01% (magenta). The sidechains and backbone of ACE2 amino acids that contact the RBD are shown on the figure and colored magenta. (B) Surface representation of the RBD ACE2 binding site (pdbid 6m0j) color coded based on amino acid variability, relative to Wuhan-1 reference sequence (see (E) for color code). (A) Ribbon diagram of the SARS-CoV-2 S RBD highlighting the 3 regions (tip, base, and knob) of the RBM that binds to ACE2. The analysis also identified a non-overlapping antibody pair (1213HD1) that bound to all SARS-CoV-2 RBD variants evaluated, representing an excellent therapeutic option for treatment of SARS-CoV-2 WT and VoC strains.ĪCE2 binding affinity RBD SARS-CoV-2 epitope mapping neutralizing antibodies variant of concern.Ĭopyright © 2021 Deshpande, Harris, Martinez-Sobrido, Kobie and Walter.ĭetails of the RBD – ACE2 interaction and frequency of RBD mutations.

Thus, the L452R mutant, associated with the SARS-CoV-2 California VoC (B.1.427/B.1.429-California), has evolved to enhance ACE2 binding, while simultaneously disrupting C1 and C2 NAb classes. While slightly less disruptive to NAb binding, L452R enhanced ACE2 binding affinity. RBD variants E484K and N501Y exhibited ACE2 binding equivalent to a Wuhan-1 reference SARS-CoV-2 RBD. Of 9 single RBD mutants evaluated, K417T, E484K, and N501Y disrupted binding of 65% of the NAbs evaluated, consistent with the assignment of the SARS-CoV-2 P.1 Japan/Brazil strain as a variant of concern (VoC). NAb and ACE2 binding studies confirmed the NAb classifications and determined whether the RBD variants enhanced ACE2 binding to promote viral infectivity, and/or disrupted NAb binding to evade the host immune response. Naturally occurring SARS-CoV-2 RBD sequence variation was also quantified to predict NAb binding sensitivities to the RBD-variants.

#Rbd cd collection series

In this report, NAb-RBD binding epitopes in the protein databank were classified as C1, C1D, C2, C3, or C4, using a RBD binding profile (BP), based on NAb-specific RBD buried surface area and used to predict the binding epitopes of a series of uncharacterized NAbs. The SARS-CoV-2 S RBD is a major target of neutralizing antibodies (NAbs) that block RBD - ACE2 interactions. The receptor binding domain (RBD) of the SARS-CoV-2 Spike (S) protein binds to cell surface angiotensin converting enzyme type-II (ACE2) to initiate viral attachment and ultimately viral pathogenesis. Severe acute respiratory syndrome coronavirus-2 (SAR-CoV-2) causes coronavirus disease 2019 (COVID19) that is responsible for short and long-term disease, as well as death, in susceptible hosts.