Screening of Clinically Approved and Investigation Drugs as Potential Inhibitors of SARS-CoV-2: A Combined in silico and inâ
vitro Study.
Mol Inform
; 41(2): e2100062, 2022 02.
Article
in English
| MEDLINE | ID: covidwho-1412241
ABSTRACT
In the current study, we used 7922 FDA approved small molecule drugs as well as compounds in clinical investigation from NIH's NPC database in our drug repurposing study. SARS-CoV-2 main protease as well as Spike protein/ACE2 targets were used in virtual screening and top-100 compounds from each docking simulations were considered initially in short molecular dynamics (MD) simulations and their average binding energies were calculated by MM/GBSA method. Promising hit compounds selected based on average MM/GBSA scores were then used in long MD simulations. Based on these numerical calculations following compounds were found as hit inhibitors for the SARS-CoV-2 main protease Pinokalant, terlakiren, ritonavir, cefotiam, telinavir, rotigaptide, and cefpiramide. In addition, following 3 compounds were identified as inhibitors for Spike/ACE2 Denopamine, bometolol, and rotigaptide. In order to verify the predictions of in silico analyses, 4 compounds (ritonavir, rotigaptide, cefotiam, and cefpiramide) for the main protease and 2 compounds (rotigaptide and denopamine) for the Spike/ACE2 interactions were tested by inâ
vitro experiments. While the concentration-dependent inhibition of the ritonavir, rotigaptide, and cefotiam was observed for the main protease; denopamine was effective at the inhibition of Spike/ACE2 binding.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Drugs, Investigational
/
Drug Repositioning
/
SARS-CoV-2
Type of study:
Prognostic study
Topics:
Traditional medicine
Limits:
Humans
Language:
English
Journal:
Mol Inform
Year:
2022
Document Type:
Article
Affiliation country:
Minf.202100062
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