scholarly journals Prospective mapping of viral mutations that escape antibodies used to treat COVID-19

Science ◽  
2021 ◽  
Vol 371 (6531) ◽  
pp. 850-854 ◽  
Author(s):  
Tyler N. Starr ◽  
Allison J. Greaney ◽  
Amin Addetia ◽  
William W. Hannon ◽  
Manish C. Choudhary ◽  
...  
Keyword(s):  
Amino Acid ◽  
Infected Patient ◽  
Viral Escape ◽  
Single Amino Acid ◽  
Receptor Binding Domain ◽  
Amino Acid Mutation ◽  
The Individual ◽  
Viral Surveillance ◽  
Single Amino Acid Mutation

Antibodies are a potential therapy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the risk of the virus evolving to escape them remains unclear. Here we map how all mutations to the receptor binding domain (RBD) of SARS-CoV-2 affect binding by the antibodies in the REGN-COV2 cocktail and the antibody LY-CoV016. These complete maps uncover a single amino acid mutation that fully escapes the REGN-COV2 cocktail, which consists of two antibodies, REGN10933 and REGN10987, targeting distinct structural epitopes. The maps also identify viral mutations that are selected in a persistently infected patient treated with REGN-COV2 and during in vitro viral escape selections. Finally, the maps reveal that mutations escaping the individual antibodies are already present in circulating SARS-CoV-2 strains. These complete escape maps enable interpretation of the consequences of mutations observed during viral surveillance.

scholarly journals Prospective mapping of viral mutations that escape antibodies used to treat COVID-19

2020 ◽  
Author(s):  
Tyler N. Starr ◽  
Allison J. Greaney ◽  
Amin Addetia ◽  
William W. Hannon ◽  
Manish C. Choudhary ◽  
...  
Keyword(s):  
Amino Acid ◽  
Receptor Binding ◽  
Infected Patient ◽  
Viral Escape ◽  
Single Amino Acid ◽  
Receptor Binding Domain ◽  
Amino Acid Mutation ◽  
Frontline Therapy ◽  
Viral Surveillance ◽  
Single Amino Acid Mutation

Antibodies are becoming a frontline therapy for SARS-CoV-2, but the risk of viral evolutionary escape remains unclear. Here we map how all mutations to SARS-CoV-2’s receptor-binding domain (RBD) affect binding by the antibodies in Regeneron’s REGN-COV2 cocktail and Eli Lilly’s LY-CoV016. These complete maps uncover a single amino-acid mutation that fully escapes the REGN-COV2 cocktail, which consists of two antibodies targeting distinct structural epitopes. The maps also identify viral mutations that are selected in a persistently infected patient treated with REGN-COV2, as well as in lab viral escape selections. Finally, the maps reveal that mutations escaping each individual antibody are already present in circulating SARS-CoV-2 strains. Overall, these complete escape maps enable immediate interpretation of the consequences of mutations observed during viral surveillance.

scholarly journals Deactivation and Mislocalization of a kinase protein induced by a single amino acid mutation on the proton transport catalytic aspartic acid

2018 ◽  
Author(s):  
Yang Zhang
Keyword(s):  
Amino Acid ◽  
Aspartic Acid ◽  
Proton Transport ◽  
Kinase Activity ◽  
Single Amino Acid ◽  
Phosphoryl Transfer ◽  
Amino Acid Mutation ◽  
Functional Changes ◽  
Single Amino Acid Mutation

AbstractRhoptry protein 18 (ROP18) is a major determinant of strain-specific virulence in Toxoplasma gondii. The kinase activity of ROP18 is required for acute virulence, while the aspartate in the catalytic loop of ROP18 is considered essential for phosphoryl transfer. We showed that a single amino acid mutation at the catalytic aspartate residue (D409A mutation) significantly altered ROP18 kinase activity in vitro, and abolished ROP18-mediated ATF6β degradation. Furthermore, the investigated single amino acid mutation in ROP18 led to alternation of subcellular localization of ROP18 protein. Structural modeling analysis suggests that these phenotypes might be associated with D409A mutation induced conformation changes in ROP18.Our findings demonstrate that a single amino acid mutation on the proton transport catalytic aspartic acid induced conformational alternations in ROP18 resulting in functional changes associated with ROP18 protein.

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