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. 2021 Sep;39(14):4949-4961.
doi: 10.1080/07391102.2020.1782265. Epub 2020 Jun 24.

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

Mallikarjuna Nimgampalle  1 , Vasudharani Devanathan  1 , Ambrish Saxena  2
Affiliations

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

Mallikarjuna Nimgampalle et al. J Biomol Struct Dyn. 2021 Sep.

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.Communicated by Ramaswamy H. Sarma.

Keywords: COVID-19; Chloroquine derivatives; Hydroxychloroquine; SARS-CoV-2; molecular docking.

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Figures

Figure 1.
Figure 1.
Hydroxychloroquine and CQN2H showing various interactions with Non-structural protein-3.
Figure 2.
Figure 2.
Hydroxychloroquine and CQN21D showing various interactions with Main protease.
Figure 3.
Figure 3.
Hydroxychloroquine and CQN2H showing various interactions with RNA dependent RNA polymerase.
Figure 4.
Figure 4.
Hydroxychloroquine and CQN1B showing various interactions with SARS-CoV-2 spike glycoprotein.
Figure 5.
Figure 5.
Hydroxychloroquine and CQN1A showing various interactions with spike protein – Receptor Binding Domain.
Figure 6.
Figure 6.
Hydroxychloroquine and CQN2I showing various interactions with ADP-ribose-1 monophosphatase.
Figure 7.
Figure 7.
Hydroxychloroquine and CQN2H showing various interactions with Non-structural protein-9 (Replicase protein).
See this image and copyright information in PMC

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