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. 2021 Oct;14(10):1454-1460.
doi: 10.1016/j.jiph.2021.07.012. Epub 2021 Jul 21.

Rilpivirine inhibits SARS-CoV-2 protein targets: A potential multi-target drug

Fuad Ameen  1 , Estari Mamidala  2 , Rakesh Davella  2 , Shravan Vallala  3
Affiliations

Rilpivirine inhibits SARS-CoV-2 protein targets: A potential multi-target drug

Fuad Ameen et al. J Infect Public Health. 2021 Oct.

Abstract

Background: COVID-19 disease caused by SARS-CoV-2 is lacking efficient medication although certain medications are used to relief its symptoms.

Objectives: We tested an FDA-approved antiviral medication namely rilpivirine to find a drug against SARS-CoV-2.

Methods: The inhibition of rilpivirine against multiple SARS-CoV-2 therapeutic targets was studied using in silico method. The binding attraction of the protein-ligand complexes were calculated using molecular docking analysis.

Results: Docking rilpivirine with main protease (Mpro), papin like protease (PLpro), sprike protein (Spro), human angiotensin converting enzyme-2 (ACE2), and RNA dependent-RNA polymerase (RdRp) yielded binding energies of -8.07, -8.40, -7.55, -9.11, and -8.69 kcal/mol, respectively. The electrostatic interaction is the key force in stabilizing the RdRp-rilpivirine complex, while van der Waals interaction dominates in the ACE2 rilpivirine case. Our findings suggest that rilpivirine can inhibit SARS-CoV-2 replication by targeting not only ACE2, but also RdRp and other targets, and therefore, it can be used to invoke altered mechanisms at the pre-entry and post-entry phases.

Conclusion: As a result of our in silico molecular docking study, we suggest that rilpivirine is a compound that could act as a powerful inhibitor against SARS-CoV-2 targets. Although in vitro and in vivo experiments are needed to verify this prediction we believe that this antiviral drug may be used in preclinical trials to fight against SARS coronavirus.

Keywords: ACE2; Docking; In silico; RdRp; Rilpivirine; SARS-CoV-2.

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Figures

Fig. 1
Fig. 1
3D structure of rilpivirine (CID: 6451164).
Fig. 2
Fig. 2
3D structures of SARS-CoV-2 therapeutic target proteins.
Fig. 3
Fig. 3
Illustration of rilpivirine inhibition against the SARS-CoV-2 target proteins: ACE2, RdRp, Spike Glycoprotein, Mpro and PL-pro.
Fig. 4
Fig. 4
Molecular interactions between ACE2 receptor protein (PDB ID: 6CS2, D Chain) and rilpivirine.
Fig. 5
Fig. 5
Molecular interactions between SARS-CoV-2 RdRp (PDB ID: 6NUR) and rilpivirine.
Fig. 6
Fig. 6
Molecular interactions between SARS-CoV-2 PLpro (PDB ID: 4OVZ) and rilpivirine.
Fig. 7
Fig. 7
Molecular interactions between SARS-CoV-2 Mpro (PDB ID: 6LU7) and rilpivirine.
Fig. 8
Fig. 8
Molecular interactions between SARS-CoV-2 Spro (PDB ID: 6CS2, A Chain) and rilpivirine.
See this image and copyright information in PMC

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