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. 2021 Jul;39(10):3469-3479.
doi: 10.1080/07391102.2020.1765876. Epub 2020 May 15.

Repurposing of chloroquine and some clinically approved antiviral drugs as effective therapeutics to prevent cellular entry and replication of coronavirus

Akinwunmi O Adeoye  1 , Babatunde Joseph Oso  2 , Ige Francis Olaoye  2 , Habibu Tijjani  3 , Ahmed I Adebayo  4
Affiliations

Repurposing of chloroquine and some clinically approved antiviral drugs as effective therapeutics to prevent cellular entry and replication of coronavirus

Akinwunmi O Adeoye et al. J Biomol Struct Dyn. 2021 Jul.

Erratum in

  • Correction notice.
    [No authors listed] [No authors listed] J Biomol Struct Dyn. 2020 Aug;38(13):i. doi: 10.1080/07391102.2020.1792707. Epub 2020 Jul 7. J Biomol Struct Dyn. 2020. PMID: 32633620 Free PMC article. No abstract available.

Abstract

The reemergence of coronavirus prompts the need for the development of effective therapeutics to prevent the cellular entry and replication of coronavirus. This study demonstrated the putative inhibitory potential of lopinavir, remdesivir, oseltamir, azithromycin, ribavirin, and chloroquine towards V-ATPase, protein kinase A, SARS-CoV spike glycoprotein/ACE-2 complex and viral proteases. The pharmacodynamic and pharmacokinetic properties were predicted through the pkCSM server while the corresponding binding affinity of the selected drugs towards the proteins was computed using AutodockVina Screening tool. The ADMET properties revealed all the drugs possess drug-like properties. Lopinavir has the highest binding affinities to the pocket site of SARS-CoV spike glycoprotein/ACE-2 complex, cyclic AMP-dependent protein kinase A and 3-Chymotrypsin like protease while redemsivir has the highest binding affinities for vacuolar proton-translocating ATPase (V-ATPase) and papain-like proteins. The amino acids Asp269, Leu370, His374, and His345 were predicted as the key residues for lopinavir binding to human SARS-CoV spike glycoprotein/ACE-2 complex while His378, Tyr515, Leu73, Leu100, Phe32 and Phe40 for remdesivir and Tyr510, Phe504, Met62, Tyr50, and His378 were predicted for azithromycin as the key residues for binding to SARS-CoV spike glycoprotein/ACE-2 complex. Moreover, it was also observed that chloroquine has appreciable binding affinities for 3-Chymotrpsin- like protease and cyclic AMP-dependent protein kinase A when compared to Oseltamivir and ribavirin. The study provided evidence suggesting putative repurposing of the selected drugs for the development of valuable drugs for the prevention of cellular entry and replication of coronavirus.Communicated by Ramaswamy H. Sarma.

Keywords: Autodock tool; Coronavirus; antiviral drugs; chloroquine; pkCSM tool.

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Figures

Figure 1.
Figure 1.
Docking view of the drugs in the binding sites of PLpro: (A) Azithromycin, (B) Chloroquine (C) Lopinavir (D) Oseltamivir, (E)Remdesivir, (F) Ribavirin.
Figure 2.
Figure 2.
Docking view of the drugs in the binding sites of 3CLPro: (A) Azithromycin, (B) Chloroquine (C) Lopinavir (D) Oseltamivir, (E) Remdesivir, (F) Ribavirin.
Figure 3.
Figure 3.
Docking view of the drugs in the binding sites of SARS COV-SPIKE GLYCO/ACE2: (A) Azithromycin, (B) Chloroquine (C) Lopinavir (D) Oseltamivir, (E)Remdesivir, (F) Ribavirin.
Figure 4.
Figure 4.
Docking view of the drugs in the binding sites of PKA: (A) Azithromycin, (B) Chloroquine (C) Lopinavir (D) Oseltamivir, (E) Remdesivir, (F) Ribavirin.
Figure 5.
Figure 5.
Docking view of the drugs in the binding sites of V-ATPase: (A) Azithromycin, (B) Chloroquine (C) Lopinavir (D) Oseltamivir, (E) Remdesivir, (F) Ribavirin.
Figure 6.
Figure 6.
Molecular dynamics simulation showing (A) deformability, (B) B-factor, (C) eigenvalues, (D) variance, (E) covariance map (F) elastic network of (i) PLpro (ii) 3CLpro (iii) SARS-CoV spike glycoprotein/ACE-2 complex (iv) cAMP-PKA (v) V-ATPase docked complexes.
See this image and copyright information in PMC

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