Prediction of potential inhibitors for RNA-dependent RNA polymerase of SARS-CoV-2 using comprehensive drug repurposing and molecular docking approach

• Main Authors: Parvez, Md. Sorwer Alam, Karim, Md. Adnan, Hasan, Mahmudul, Jaman, Jomana, Karim, Ziaul, Tahsin, Tohura, Hasan, Md. Nazmul, Hosen, Mohammad Jakir
• Format: Journal Article
• Language: English
• Published: 15-04-2020
• Subjects: Quantitative Biology - Biomolecules
• DOI: 10.48550/arxiv.2004.07086

International Journal of Biological Macromolecules 163 (2020)
1787-1797 The pandemic prevalence of COVID-19 has become a very serious global health
issue. Scientists all over the world have been heavily invested 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 ZINC
09883305) 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
investigated to check the pharmacokinetics and drug-likeness properties of the
two compounds. Comparative structural analysis of protein-inhibitor complexes
revealed that positions of the amino acid Y32, K47, Y122, Y129, H133, N138,
D140, T141, S709 and N781 are crucial for drug surface hotspot in the RdRp of
SARS-CoV-2.