Virtual screening based on molecular docking of possible inhibitors of Covid-19 main protease

Emanuelle Machado Marinho; João Batista de Andrade Neto; Jacilene Silva; Cecília Rocha da Silva; Bruno Coelho Cavalcanti; Emmanuel Silva Marinho; Hélio Vitoriano Nobre Júnior

doi:10.1016/j.micpath.2020.104365

Virtual screening based on molecular docking of possible inhibitors of Covid-19 main protease

Microb Pathog. 2020 Nov:148:104365. doi: 10.1016/j.micpath.2020.104365. Epub 2020 Jun 30.

Authors

Emanuelle Machado Marinho¹, João Batista de Andrade Neto², Jacilene Silva³, Cecília Rocha da Silva⁴, Bruno Coelho Cavalcanti⁵, Emmanuel Silva Marinho³, Hélio Vitoriano Nobre Júnior⁶

Affiliations

¹ Department of Analytical Chemistry and Physical Chemistry, Group of Theoretical Chemistry (GQT), Science Center, Federal University of Ceará, Fortaleza, CE, 60.455-760, Brazil.
² School of Pharmacy, Laboratory of Bioprospection in Antimicrobial Molecules (LABIMAN), Federal University of Ceara, Fortaleza, CE, Brazil; Christus University Center (UNICHRISTUS), Fortaleza, CE, Brazil; Drug Research and Development Center, Federal University of Ceará, Fortaleza, CE, Brazil.
³ Department of Chemistry, Group of Theoretical Chemistry and Electrochemistry (GQTE), State University of Ceará, Limoeiro do Norte, Ceará, Brazil.
⁴ School of Pharmacy, Laboratory of Bioprospection in Antimicrobial Molecules (LABIMAN), Federal University of Ceara, Fortaleza, CE, Brazil; Drug Research and Development Center, Federal University of Ceará, Fortaleza, CE, Brazil.
⁵ Drug Research and Development Center, Federal University of Ceará, Fortaleza, CE, Brazil.
⁶ School of Pharmacy, Laboratory of Bioprospection in Antimicrobial Molecules (LABIMAN), Federal University of Ceara, Fortaleza, CE, Brazil; Drug Research and Development Center, Federal University of Ceará, Fortaleza, CE, Brazil. Electronic address: label_ufc@yahoo.com.br.

Abstract

Coronavirus (COVID-19) is an enveloped RNA virus that is diversely found in humans and that has now been declared a global pandemic by the World Health Organization. Thus, there is an urgent need to develop effective therapies and vaccines against this disease. In this context, this study aimed to evaluate in silico the molecular interactions of drugs with therapeutic indications for treatment of COVID-19 (Azithromycin, Baricitinib and Hydroxychloroquine) and drugs with similar structures (Chloroquine, Quinacrine and Ruxolitinib) in docking models from the SARS-CoV-2 main protease (M-pro) protein. The results showed that all inhibitors bound to the same enzyme site, more specifically in domain III of the SARS-CoV-2 main protease. Therefore, this study allows proposing the use of baricitinib and quinacrine, in combination with azithromycin; however, these computer simulations are just an initial step for conceiving new projects for the development of antiviral molecules.

Keywords: COVID-19; Inhibitors; Molecular docking.

MeSH terms

Antiviral Agents / chemistry*
Antiviral Agents / pharmacology*
Binding Sites / drug effects
COVID-19 / virology*
COVID-19 Drug Treatment
Coronavirus 3C Proteases / antagonists & inhibitors*
Coronavirus 3C Proteases / chemistry*
Cysteine Endopeptidases / chemistry
Cysteine Proteinase Inhibitors / chemistry
Cysteine Proteinase Inhibitors / pharmacology
Drug Discovery / methods
Drug Evaluation, Preclinical / methods
Humans
Molecular Docking Simulation
Protease Inhibitors / chemistry
Protease Inhibitors / pharmacology
SARS-CoV-2 / drug effects*
SARS-CoV-2 / enzymology

Substances

Antiviral Agents
Cysteine Proteinase Inhibitors
Protease Inhibitors
Cysteine Endopeptidases
Coronavirus 3C Proteases