Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Apr 30;16(4):301-306.
doi: 10.6026/97320630016301. eCollection 2020.

Repurposing of known anti-virals as potential inhibitors for SARS-CoV-2 main protease using molecular docking analysis

Mohammed Hakmi  1 , El Mehdi Bouricha  1 , Ilham Kandoussi  1 , Jaouad El Harti  2 , Azeddine Ibrahimi  1
Affiliations

Repurposing of known anti-virals as potential inhibitors for SARS-CoV-2 main protease using molecular docking analysis

Mohammed Hakmi et al. Bioinformation. .

Abstract

The new SARS-CoV-2 coronavirus is the causative agent of the COVID-19 pandemic outbreak that affected more than 190 countries worldwide with more than 292,000 confirmed cases and over 12,700 deaths. There is at the moment no vaccine or effective treatment for this disease which constitutes a serious global health problem. It is of interest to use a structure based virtual screening approach for the identification of potential inhibitors of the main protease of SARS-CoV-2 (Mpro) from antiviral drugs used to treat other viral disease such as human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections. The crystallographic structure with PDB ID: 6LU7 of Mpro in complex with the inhibitor N3 was used as a model in the virtual screening of 33 protease inhibitors collected from the ChEMBL chemical database. Molecular docking analysis was performed using the standard AutoDock vina protocol followed by ranking and selection of compounds based on their binding affinity. We report 10 candidates with optimal binding features to the active site of the protease for further consideration as potential drugs to treat patients infected with the emerging COVID-19 disease.

Keywords: COVID-19; SARS-Cov-2; inhibitors; protease; virtual screening.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Surface representation of SARS-CoV-2 Mpro protomer showing its domain organization (PDB code 6LU7). The substrate binding site is located in the pocket between domain I (blue) and II (green). Domain III is colored in red and the co-crystallized bound inhibitor N3 is represented by yellow sticks.
Figure 2
Figure 2
Binding modes of the ten selected candidates in the substrate-binding site of SARS-CoV-2 Mpro. (A) Paritaprevir; (B) Ciluprevir; (C) Simeprevir; (D) Deldeprevir; (E) Indinavir; (F) Saquinavir; (G) Faldaprevir; (H) Brecanavir; (I) Grazoprevir; (J) Lopinavir; (K) Inhibitor N3; (L) Darunavir. The catalytic dyad Cys145-His41 is colored in red and blue respectively.
Figure 3
Figure 3
Molecular contacts between the selected candidates and the residues of the substrate-binding pocket of SARS-CoV-2 Mpro.(A), Paritaprevir.(B),Ciluprevir.(C), Simeprevir. (D), Deldeprevir. The four compounds established multiple hydrogen bonding and hydrophobic interaction with the residues of the substrate-binding pocket of Mpro. Interactions with the catalytic His41 were observed in the four compounds. Paritaprevir and Simeprevir interacted with the catalytic Cys145 as well throught a hydrophobic contact and a hydrogen bond respectively.
Figure 4
Figure 4
Molecular contacts between the selected candidates and the residues of the substrate binding pocket of SARS-CoV-2 Mpro.(E),Indinavir.(F),Saquinavir.(G),Faldaprevir. (H), Brecanavir. The four compounds were stabilized inside the substrate-binding pocket of Mpro by a network of hydrogen bonds and hydrophobic contacts. Interactions with the catalytic dyad Cis-145-His41 were observed in Indinavir, Saquinavir and Faldaprevir; however, Brecanavir interacted only with the catalytic Cys145.
Figure 5
Figure 5
Molecular contacts between the selected candidates and the residues of the substrate binding pocket of SARS-CoV-2 Mpro.(I),Grazoprevir.(J),Lopinavir. More hydrophobic interactions than hydrogen bonds were observed in Grazoprevir, which interacted with both catalytic residues Cys145 (1 hydrophobic contact) and His41 (1 hydrogen bond and 1 Pi sulfur bond). Lopinavir interacted only with His-41 through a Pi-Pi stacked interaction and a hydrophobic contact.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Lu H, et al. Journal of medical virology. 2020;92:401. - PMC - PubMed
    1. Bogoch II, et al. Journal of travel medicine. . 2020;27:1.
    1. Yuen KS, et al. Cell and bioscience. . 2020;10:40. - PMC - PubMed
    1. https://www.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd4029942....
    1. Cunningham AC, et al. Critical care (London, England). . 2020;24:91. - PMC - PubMed

LinkOut - more resources

-