Revealing the Threat of Emerging SARS-CoV-2 Mutations to Antibody Therapies.
J Mol Biol
; 433(18): 167155, 2021 09 03.
Article
in English
| MEDLINE | ID: covidwho-1309295
Preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
ABSTRACT
The ongoing massive vaccination and the development of effective intervention offer the long-awaited hope to end the global rage of the COVID-19 pandemic. However, the rapidly growing SARS-CoV-2 variants might compromise existing vaccines and monoclonal antibody (mAb) therapies. Although there are valuable experimental studies about the potential threats from emerging variants, the results are limited to a handful of mutations and Eli Lilly and Regeneron mAbs. The potential threats from frequently occurring mutations on the SARS-CoV-2 spike (S) protein receptor-binding domain (RBD) to many mAbs in clinical trials are largely unknown. We fill the gap by developing a topology-based deep learning strategy that is validated with tens of thousands of experimental data points. We analyze 796,759 genome isolates from patients to identify 606 non-degenerate RBD mutations and investigate their impacts on 16 mAbs in clinical trials. Our findings, which are highly consistent with existing experimental results about Alpha, Beta, Gamma, Delta, Epsilon, and Kappa variants shed light on potential threats of 100 most observed mutations to mAbs not only from Eli Lilly and Regeneron but also from Celltrion and Rockefeller University that are in clinical trials. We unveil, for the first time, that high-frequency mutations R346K/S, N439K, G446V, L455F, V483F/A, F486L, F490L/S, Q493L, and S494P might compromise some of mAbs in clinical trials. Our study gives rise to a general perspective about how mutations will affect current vaccines.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
SARS-CoV-2
/
COVID-19 Drug Treatment
/
Antibodies, Monoclonal
/
Mutation
Type of study:
Prognostic study
Topics:
Vaccines
/
Variants
Limits:
Humans
Language:
English
Journal:
J Mol Biol
Year:
2021
Document Type:
Article
Affiliation country:
J.jmb.2021.167155
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