Computational Guided Drug Repurposing for Targeting 2'-O-Ribose Methyltransferase of SARS-CoV-2

Kedar Sharma, Sudhir Morla, Arun Goyal, Sachin Kumar

10.1016/j.lfs.2020.118169

Research curated

Abstract

Aims: The recent outbreak of pandemic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led the world towards a global health emergency. Currently, no proper medicine or effective treatment strategies are available; therefore, repurposing of FDA approved drugs may play an important role in overcoming the situation. Materials and methods: The SARS-CoV-2 genome encodes for 2-O-methyltransferase (2′OMTase), which plays a key role in methylation of viral RNA for evading host immune system. In the present study, the protein sequence of 2′OMTase of SARS-CoV-2 was analyzed, and its structure was modeled by a comparative modeling approach and validated. The library of 3000 drugs was screened against the active site of 2′OMTase followed by re-docking analysis. The apo and ligand-bound 2′OMTase were further validated and analyzed by using molecular dynamics simulation. Key findings: The modeled structure displayed the conserved characteristic fold of class I MTase family. The quality assessment analysis by SAVES server reveals that the modeled structure follows protein folding rules and of excellent quality. The docking analysis displayed that the active site of 2′OMTase accommodates an array of drugs, which includes alkaloids, antivirals, cardiac glycosides, anticancer, steroids, and other drugs. The redocking and MD simulation analysis of the best 5 FDA approved drugs reveals that these drugs form a stable conformation with the 2′OMTase. Significance: The results suggested that these drugs may be used as potential inhibitors for 2′OMTase for combating the SARS-CoV-2 infection.

Source: PubMed

Related molecules

Name	Synonyms	Genes
Chlorthalidone
Eribulin
Triamcinolone acetonide
Putative 2'-O-methyl transferase	2’-O-Ribose methyltransferase, Non-structural protein 16, Nonstructural protein 16, nsp16	rep, ORF1a-1b
Saquinavir
Ergotamine
Teniposide
Irinotecan
Zafirlukast
Dihydroergotamine
Digitoxin

Related interactions

Target	Drug	Type	Result
Putative 2'-O-methyl transferase	Digitoxin	Computational	positive
Putative 2'-O-methyl transferase	Zafirlukast	Computational	positive
Putative 2'-O-methyl transferase	Saquinavir	Computational	positive
Putative 2'-O-methyl transferase	Dihydroergotamine	Computational	positive
Putative 2'-O-methyl transferase	Chlorthalidone	Computational	positive
Putative 2'-O-methyl transferase	Irinotecan	Computational	positive
Putative 2'-O-methyl transferase	Teniposide	Computational	positive
Putative 2'-O-methyl transferase	Eribulin	Computational	positive
Putative 2'-O-methyl transferase	Ergotamine	Computational	positive
Putative 2'-O-methyl transferase	Triamcinolone acetonide	Computational	positive