Repurposing drugs for treatment of SARS-CoV-2 infection: computational design insights into mechanisms of action

Shubhangi Kandwal, Darren Fayne

10.1080/07391102.2020.1825232

Research curated

Abstract

The COVID-19 pandemic has negatively affected human life globally. It has led to economic crises and health emergencies across the world, spreading rapidly among the human population and has caused many deaths. Currently, there are no treatments available for COVID-19 so there is an urgent need to develop therapeutic interventions that could be used against the novel coronavirus infection. In this research, we used computational drug design technologies to repurpose existing drugs as inhibitors of SARS-CoV-2 viral proteins. The Broad Institute’s Drug Repurposing Hub consists of in-development/approved drugs and was computationally screened to identify potential hits which could inhibit protein targets encoded by the SARS-CoV-2 genome. By virtually screening the Broad collection, using rationally designed pharmacophore features, we identified molecules which may be repurposed against viral nucleocapsid and non-structural proteins. The pharmacophore features were generated after careful visualisation of the interactions between co-crystalised ligands and the protein binding site. The ChEMBL database was used to determine the compound’s level of inhibition of SARS-CoV-2 and correlate the predicted viral protein target with whole virus in vitro data. The results from this study may help to accelerate drug development against COVID-19 and the hit compounds should be progressed through further in vitro and in vivo studies on SARS-CoV-2.

Source: PubMed

Related molecules

Name	Synonyms	Genes
Isepamicin
(-)-Epigallocatechin gallate
Procyanidin B-2
Olomoucine
Sapropterin
Tetrahydrofolic acid
Adenosine phosphate	5'-Adenosine monophosphate, 5'-Adenylic acid, 5'-AMP, Adenylate, Adenosine-5'P, AMP, Adenylate
Varespladib
hexonic acid
Citric acid
Stepronin
Calcium gluceptate
Pirenoxine
Midafotel
Maltobionic acid
RNA dependent RNA polymerase	RDR, viral RNA polymerase, RdRp, nsp12	rep, ORF1a-1b, RdRp
nsp16/nsp10 complex		rep, ORF1a-1b
Uridylate-specific endoribonuclease	NSP15, Non-structural protein 15, Nonstructural protein 15, NendoU, endoRNAse	rep, ORF1a-1b
Paromomycin
Streptomycin
Rutin
NTD-N-protein	N terminal domain of Nucleocapsid protein
Papain-like proteinases 1/2	Non-structural protein 3, papain like viral protease, nsp3, PL1-PRO/PL2-PRO, PLP1/PLP2, p195, Plpro	rep, ORF1a-1b

Related interactions

Target	Drug	Type	Result
Papain-like proteinases 1/2	Isepamicin	Computational	positive
Papain-like proteinases 1/2	Streptomycin	Computational	positive
RNA dependent RNA polymerase	Rutin	Computational	positive
RNA dependent RNA polymerase	(-)-Epigallocatechin gallate	Computational	positive
RNA dependent RNA polymerase	Procyanidin B-2	Computational	positive
nsp16/nsp10 complex	Paromomycin	Computational	positive
Uridylate-specific endoribonuclease	Olomoucine	Computational	positive
Uridylate-specific endoribonuclease	Sapropterin	Computational	positive
Uridylate-specific endoribonuclease	Tetrahydrofolic acid	Computational	positive
Uridylate-specific endoribonuclease	Adenosine phosphate	Computational	positive
NTD-N-protein	Varespladib	Computational	positive
NTD-N-protein	hexonic acid	Computational	positive
NTD-N-protein	Citric acid	Computational	positive
NTD-N-protein	Stepronin	Computational	positive
NTD-N-protein	Calcium gluceptate	Computational	positive
NTD-N-protein	Pirenoxine	Computational	positive
NTD-N-protein	Midafotel	Computational	positive
NTD-N-protein	Maltobionic acid	Computational	positive