501Y.V2 and 501Y.V3 variants of SARS-CoV-2 lose binding to bamlanivimab in vitro.
The newly emerging variants of SARS-CoV-2 from South Africa (B.1.351/501Y.V2) and Brazil (P.1/501Y.V3) have led to a higher infection rate and reinfection of COVID-19 patients. We found that the mutations K417N, E484K, and N501Y within the receptor-binding domains (RBDs) of the virus could confer ~2-fold higher binding affinity to the ... human receptor, angiotensin converting enzyme 2 (ACE2), compared to the wildtype RBD. The mutated version of RBD also completely abolishes the binding of bamlanivimab, a therapeutic antibody, in vitro. Detailed analysis shows that the ~10-fold gain of binding affinity between ACE2 and Y501-RBD, which also exits in the high contagious variant B.1.1.7/501Y.V1 from the United Kingdom, is compromised by additional introduction of the K417/N/T mutation. Mutation of E484K leads to the loss of bamlanivimab binding to RBD, although this mutation does not affect the binding between RBD and ACE2.
Mesh Terms:
Angiotensin-Converting Enzyme 2, Antibodies, Monoclonal, Humanized, Antiviral Agents, Binding Sites, COVID-19, COVID-19 Drug Treatment, Host-Pathogen Interactions, Humans, Molecular Docking Simulation, Mutation, Protein Binding, Protein Interaction Domains and Motifs, Receptors, Virus, SARS-CoV-2
Angiotensin-Converting Enzyme 2, Antibodies, Monoclonal, Humanized, Antiviral Agents, Binding Sites, COVID-19, COVID-19 Drug Treatment, Host-Pathogen Interactions, Humans, Molecular Docking Simulation, Mutation, Protein Binding, Protein Interaction Domains and Motifs, Receptors, Virus, SARS-CoV-2
MAbs
Date: Jun. 03, 2021
PubMed ID: 34074219
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