Insilico drug repurposing using FDA approved drugs against Membrane protein of SARS-CoV-2.
J Pharm Sci
; 110(6): 2346-2354, 2021 06.
Article
in English
| MEDLINE | ID: covidwho-1121342
ABSTRACT
The novel coronavirus (SARS-CoV-2) outbreak has started taking away the millions of lives worldwide. Identification of known and approved drugs against novel coronavirus disease (COVID-19) seems to be an urgent need for the repurposing of the existing drugs. So, here we examined a safe strategy of using approved drugs of SuperDRUG2 database against modeled membrane protein (M-protein) of SARS-CoV-2 which is essential for virus assembly by using molecular docking-based virtual screening. A total of 3639 drugs from SuperDRUG2 database and additionally 14 potential drugs reported against COVID-19 proteins were selected. Molecular docking analyses revealed that nine drugs can bind the active site of M-protein with desirable molecular interactions. We therefore applied molecular dynamics simulations and binding free energy calculation using MM-PBSA to analyze the stability of the compounds. The complexes of M-protein with the selected drugs were simulated for 50 ns and ranked according to their binding free energies. The binding mode of the drugs with M-protein was analyzed and it was observed that Colchicine, Remdesivir, Bafilomycin A1 from COVID-19 suggested drugs and Temozolomide from SuperDRUG2 database displayed desirable molecular interactions and higher binding affinity towards M-protein. Interestingly, Colchicine was found as the top most binder among tested drugs against M-protein. We therefore additionally identified four Colchicine derivatives which can bind efficiently with M-protein and have better pharmacokinetic properties. We recommend that these drugs can be tested further through in vitro studies against SARS-CoV-2 M-protein.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Pharmaceutical Preparations
/
COVID-19
Limits:
Humans
Language:
English
Journal:
J Pharm Sci
Year:
2021
Document Type:
Article
Affiliation country:
J.xphs.2021.03.004
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