Development of improved monoclonal antibodies against SARS-CoV-2 SARSCoV2 COVID19 Coronavirus MonoclonalAntibodies
By Bhavana KunkalikarSep 15 2022Reviewed by Aimee Molineux In a recent study published in the Molecular Therapy journal, researchers explored strategies for developing effective monoclonal antibodies against severe acute respiratory syndrome coronavirus 2 .
Mutations in the prototype spike receptor-binding domain have rendered antibodies ineffective in neutralizing the virus and significantly reduced the efficacy of vaccines. Therefore, the emergence of SARS-CoV-2 variants of concern as a result of the virus' ongoing evolution is explicitly relevant to the effectiveness of COVID-19 therapeutics.
All 195 amino acids found in the viral RBD are linked to mutations in the spike protein. However, not all mutations that have been proposed include ACE2 binding. A thorough mutational investigation conducted during the early phases of the COVID-19 pandemic discovered mutations in the RBD that modified ACE2 binding and/or were appropriate for antibody-based therapies.
Mutations in the ACE2 competing RBD epitopes The team modeled 3D structures of these mAbs with Beta and Gamma RBDs to examine the interface. It was discovered that E484K eliminated the electrostatic contact to complementarity-determining region H2 and CDRL3 of bamlanivimab, while K417N dissolved contacts with CDRH2 of etesevimab.
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