Structural analogues of existing anti-viral drugs inhibit SARS-CoV-2 RNA dependent RNA polymerase: A computational hierarchical investigation.
Binding free energy
COVID-19
Molecular docking
Molecular dynamics simulation
RNA dependent RNA polymerase
Virtual screening
Journal
Heliyon
ISSN: 2405-8440
Titre abrégé: Heliyon
Pays: England
ID NLM: 101672560
Informations de publication
Date de publication:
Mar 2021
Mar 2021
Historique:
received:
12
12
2020
revised:
16
02
2021
accepted:
03
03
2021
entrez:
11
3
2021
pubmed:
12
3
2021
medline:
12
3
2021
Statut:
ppublish
Résumé
The Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) became a pandemic, resulting in an exponentially increased mortality globally and scientists all over the world are struggling to find suitable solutions to combat it. Multiple repurposed drugs have already been in several clinical trials or recently completed. However, none of them shows any promising effect in combating COVID-19. Therefore, developing an effective drug is an unmet global need. RdRp (RNA dependent RNA polymerase) plays a pivotal role in viral replication. Therefore, it is considered as a prime target of drugs that may treat COVID-19. In this study, we have screened a library of compounds, containing approved RdRp inhibitor drugs that were or in use to treat other viruses (favipiravir, sofosbuvir, ribavirin, lopinavir, tenofovir, ritonavir, galidesivir and remdesivir) and their structural analogues, in order to identify potential inhibitors of SARS-CoV-2 RdRp. Extensive screening, molecular docking and molecular dynamics show that five structural analogues have notable inhibitory effects against RdRp of SARS-CoV-2. Importantly, comparative protein-antagonists interaction revealed that these compounds fit well in the pocket of RdRp. ADMET analysis of these compounds suggests their potency as drug candidates. Our identified compounds may serve as potential therapeutics for COVID-19.
Identifiants
pubmed: 33693066
doi: 10.1016/j.heliyon.2021.e06435
pii: S2405-8440(21)00540-5
pmc: PMC7934700
doi:
Types de publication
Journal Article
Langues
eng
Pagination
e06435Informations de copyright
© 2021 Published by Elsevier Ltd.
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
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