A computational study of cooperative binding to multiple SARS-CoV-2 proteins.
Sci Rep
; 11(1): 16307, 2021 08 11.
Article
in English
| MEDLINE | ID: covidwho-1354117
ABSTRACT
Structure-based drug design targeting the SARS-CoV-2 virus has been greatly facilitated by available virus-related protein structures. However, there is an urgent need for effective, safe small-molecule drugs to control the spread of the virus and variants. While many efforts are devoted to searching for compounds that selectively target individual proteins, we investigated the potential interactions between eight proteins related to SARS-CoV-2 and more than 600 compounds from a traditional Chinese medicine which has proven effective at treating the viral infection. Our original ensemble docking and cooperative docking approaches, followed by a total of over 16-micorsecond molecular simulations, have identified at least 9 compounds that may generally bind to key SARS-CoV-2 proteins. Further, we found evidence that some of these compounds can simultaneously bind to the same target, potentially leading to cooperative inhibition to SARS-CoV-2 proteins like the Spike protein and the RNA-dependent RNA polymerase. These results not only present a useful computational methodology to systematically assess the anti-viral potential of small molecules, but also point out a new avenue to seek cooperative compounds toward cocktail therapeutics to target more SARS-CoV-2-related proteins.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Viral Proteins
/
Drugs, Chinese Herbal
/
Drug Evaluation, Preclinical
/
SARS-CoV-2
/
Medicine, Chinese Traditional
Type of study:
Diagnostic study
/
Prognostic study
Topics:
Traditional medicine
/
Variants
Limits:
Animals
/
Humans
Language:
English
Journal:
Sci Rep
Year:
2021
Document Type:
Article
Affiliation country:
S41598-021-95826-6
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