SARS-CoV-2 mutations allow escape from clinical monoclonal antibodies


Monoclonal antibodies LY-CoV555 and LY-CoV016 are administered as a cocktail for the treatment and prevention of COVID-19. They target the receptor-binding domain (RBD) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein with high specificity, potentially neutralizing the virus. They have been shown to lessen viral load, and so have been approved for emergency use by the FDA in mild to moderate COVID-19 cases. However, the continuously changing genome of SARS-CoV-2 is likely to render such treatments ineffective eventually, meaning that new monoclonal antibodies specific to each strain may need to be developed.

A new research paper recently uploaded to the preprint server bioRxiv* by Jesse D. Bloom et al. (22nd Feb 2021) aims to map all of the currently circulating SARS-CoV-2 lineages with resistance towards LY-CoV555 and LY-CoV016, and document the specific mutations that confer resistance, ultimately suggesting that future monoclonal antibody cocktails should target a more diverse range of epitopes.

How was the study performed?

The research group from Fred Hutchinson Cancer Research Center and the University of Washington firstly generated yeast cells expressing nearly four thousand possible amino acid mutations of the receptor-binding domain (RBD) of wild-type SARS-CoV-2 and sorted to select mutants capable of binding with the angiotensin-converting enzyme 2 (ACE2) receptor…

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