A computational study of cooperative binding to multiple SARS-CoV-2 proteins
| Autor: | Jacob M. Remington, Kyle T. McKay, Severin T. Schneebeli, Jianing Li |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Virtual screening
Computational chemistry Science viruses Drug Evaluation Preclinical RNA-dependent RNA polymerase Plasma protein binding Computational biology Molecular Dynamics Simulation Antiviral Agents Article Structure-Activity Relationship Viral Proteins chemistry.chemical_compound Protein structure RNA polymerase Animals Humans Structure–activity relationship Medicine Chinese Traditional Flavonoids Multidisciplinary SARS-CoV-2 Chemistry fungi Computational Biology Cooperative binding RNA-Dependent RNA Polymerase Small molecule Docking (molecular) Spike Glycoprotein Coronavirus Cats Medicine Angiotensin-Converting Enzyme 2 Drugs Chinese Herbal Protein Binding |
| Zdroj: | Scientific Reports Scientific Reports, Vol 11, Iss 1, Pp 1-9 (2021) |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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