Screening of Chloroquine, Hydroxychloroquine and its derivatives for their binding affinity to multiple SARS-CoV-2 protein drug targets

Mallikarjuna Nimgampalle, Vasudharani Devanathan, Ambrish Saxena

10.1080/07391102.2020.1782265

Research curated

Abstract

Recently Chloroquine and its derivative Hydroxychloroquine have garnered enormous interest amongst the clinicians and health authorities’ world over as a potential treatment to contain COVID-19 pandemic. The present research aims at investigating the therapeutic potential of Chloroquine and its potent derivative Hydroxychloroquine against SARS-CoV-2 viral proteins. At the same time screening was performed for some chemically synthesized derivatives of Chloroquine and compared their binding efficacy with chemically synthesized Chloroquine derivatives through in silico approaches. For the purpose of the study, some essential viral proteins and enzymes were selected that are implicated in SARS-CoV-2 replication and multiplication as putative drug targets. Chloroquine, Hydroxychloroquine, and some of their chemically synthesized derivatives, taken from earlier published studies were selected as drug molecules. We have conducted molecular docking and related studies between Chloroquine and its derivatives and SARS-CoV-2 viral proteins, and the findings show that both Chloroquine and Hydroxychloroquine can bind to specific structural and non-structural proteins implicated in the pathogenesis of SARS-CoV-2 infection with different efficiencies. Our current study also shows that some of the chemically synthesized Chloroquine derivatives can also potentially inhibit various SARS-CoV-2 viral proteins by binding to them and concomitantly effectively disrupting the active site of these proteins. These findings bring into light another possible mechanism of action of Chloroquine and Hydroxychloroquine and also pave the way for further drug repurposing and remodeling.

Source: PubMed

Related molecules

Name	Synonyms	Genes
Chloroquine
Spike glycoprotein	Spike protein, S glycoprotein, S-Protein, S1, S2, S3, Peplomer protein, E2	S, ORF2
Hydroxychloroquine	HCQ, Oxichlorochine, Oxichloroquine

Related interactions

Target	Drug	Type	Result
Papain-like proteinases 1/2	Chloroquine	Computational	positive
Papain-like proteinases 1/2	Hydroxychloroquine	Computational	positive
3C-like protease	Chloroquine	Computational	positive
3C-like protease	Hydroxychloroquine	Computational	positive
RNA dependent RNA polymerase	Chloroquine	Computational	positive
RNA dependent RNA polymerase	Hydroxychloroquine	Computational	positive
Spike glycoprotein	Chloroquine	Computational	positive
Spike glycoprotein	Hydroxychloroquine	Computational	positive