Molecular rationale for SARS-CoV-2 spike circulating mutations able to escape bamlanivimab and etesevimab monoclonal antibodies.
Sci Rep
; 11(1): 20274, 2021 10 12.
Article
in English
| MEDLINE | ID: covidwho-1467137
ABSTRACT
The purpose of this work is to provide an in silico molecular rationale of the role eventually played by currently circulating mutations in the receptor binding domain of the SARS-CoV-2 spike protein (S-RBDCoV2) in evading the immune surveillance effects elicited by the two Eli Lilly LY-CoV555/bamlanivimab and LY-CoV016/etesevimab monoclonal antibodies. The main findings from this study show that, compared to the wild-type SARS-CoV-2 spike protein, mutations E484A/G/K/Q/R/V, Q493K/L/R, S494A/P/R, L452R and F490S are predicted to be markedly resistant to neutralization by LY-CoV555, while mutations K417E/N/T, D420A/G/N, N460I/K/S/T, T415P, and Y489C/S are predicted to confer LY-CoV016 escaping advantage to the viral protein. A challenge of our global in silico results against relevant experimental data resulted in an overall 90% agreement. Thus, the results presented provide a molecular-based rationale for all relative experimental findings, constitute a fast and reliable tool for identifying and prioritizing all present and newly reported circulating spike SARS-CoV-2 variants with respect to antibody neutralization, and yield substantial structural information for the development of next-generation vaccines and monoclonal antibodies more resilient to viral evolution.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Antibodies, Monoclonal, Humanized
/
Spike Glycoprotein, Coronavirus
/
SARS-CoV-2
/
COVID-19
Type of study:
Prognostic study
Topics:
Vaccines
/
Variants
Limits:
Humans
Language:
English
Journal:
Sci Rep
Year:
2021
Document Type:
Article
Affiliation country:
S41598-021-99827-3
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