Prediction of potential inhibitors for RNA-dependent RNA polymerase of SARS-CoV-2 using comprehensive drug repurposing and molecular docking approach.
Int J Biol Macromol
; 163: 1787-1797, 2020 Nov 15.
Article
in English
| MEDLINE | ID: covidwho-773658
ABSTRACT
The pandemic prevalence of COVID-19 has become a very serious global health issue. Scientists all over the world have been seriously attempting in the discovery of a drug to combat SARS-CoV-2. It has been found that RNA-dependent RNA polymerase (RdRp) plays a crucial role in SARS-CoV-2 replication, and thus could be a potential drug target. Here, comprehensive computational approaches including drug repurposing and molecular docking were employed to predict an effective drug candidate targeting RdRp of SARS-CoV-2. This study revealed that Rifabutin, Rifapentine, Fidaxomicin, 7-methyl-guanosine-5'-triphosphate-5'-guanosine and Ivermectin have a potential inhibitory interaction with RdRp of SARS-CoV-2 and could be effective drugs for COVID-19. In addition, virtual screening of the compounds from ZINC database also allowed the prediction of two compounds (ZINC09128258 and ZINC09883305) with pharmacophore features that interact effectively with RdRp of SARS-CoV-2, indicating their potentiality as effective inhibitors of the enzyme. Furthermore, ADME analysis along with analysis of toxicity was also undertaken to check the pharmacokinetics and drug-likeness properties of the two compounds. Comparative structural analysis of protein-inhibitor complexes revealed that the amino acids Y32, K47, Y122, Y129, H133, N138, D140, T141, S709 and N781 are crucial for drug surface hotspot in the RdRp of SARS-CoV-2.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Pneumonia, Viral
/
RNA-Dependent RNA Polymerase
/
Coronavirus Infections
/
Drug Repositioning
/
Betacoronavirus
Type of study:
Observational study
/
Prognostic study
Limits:
Humans
Language:
English
Journal:
Int J Biol Macromol
Year:
2020
Document Type:
Article
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