Ensemble-based screening of natural products and FDA-approved drugs identified potent inhibitors of SARS-CoV-2 that work with two distinct mechanisms

Daniel M Shadrack; Geradius Deogratias; Lucy W Kiruri; Hulda S Swai; John-Mary Vianney; Stephen S Nyandoro

doi:10.1016/j.jmgm.2021.107871

Ensemble-based screening of natural products and FDA-approved drugs identified potent inhibitors of SARS-CoV-2 that work with two distinct mechanisms

J Mol Graph Model. 2021 Jun:105:107871. doi: 10.1016/j.jmgm.2021.107871. Epub 2021 Feb 23.

Authors

Daniel M Shadrack¹, Geradius Deogratias², Lucy W Kiruri³, Hulda S Swai⁴, John-Mary Vianney⁴, Stephen S Nyandoro⁵

Affiliations

¹ Department of Health and Biomedical Sciences, School of Life Science and Bioengineering, The Nelson Mandela African Institution of Science and Technology, P.O.Box 447, Arusha, Tanzania; Department of Chemistry, Faculty of Natural and Applied Sciences, St John's University of Tanzania, P.O.Box 47, Dodoma, Tanzania. Electronic address: mshadrack@sjut.ac.tz.
² Chemistry Department, College of Natural and Applied Sciences, University of Dar es Salaam, P.O. Box 35061, Dar es Salaam, Tanzania; Department of Materials and Energy Science and Engineering, The Nelson Mandela African Institution of Science and Technology, P.O.Box 447, Arusha, Tanzania.
³ Department of Chemistry, P.O.Box 43844-00100, Kenyatta University, Nairobi, Kenya.
⁴ Department of Health and Biomedical Sciences, School of Life Science and Bioengineering, The Nelson Mandela African Institution of Science and Technology, P.O.Box 447, Arusha, Tanzania.
⁵ Chemistry Department, College of Natural and Applied Sciences, University of Dar es Salaam, P.O. Box 35061, Dar es Salaam, Tanzania. Electronic address: nyandoro@udsm.ac.tz.

Abstract

The recent outbreak of SARS-CoV-2 is responsible for high morbidity and mortality rate across the globe. This requires an urgent identification of drugs and other interventions to overcome this pandemic. Computational drug repurposing represents an alternative approach to provide a more effective approach in search for COVID-19 drugs. Selected natural product known to have antiviral activities were screened, and based on their hits; a similarity search with FDA approved drugs was performed using computational methods. Obtained drugs from similarity search were assessed for their stability and inhibition against SARS-CoV-2 targets. Diosmin (DB08995) was found to be a promising drug that works with two distinct mechanisms, preventing viral replication and viral fusion into the host cell. Isoquercetin (DB12665) and rutin (DB01698) work by inhibiting viral replication and preventing cell entry, respectively. Our analysis based on molecular dynamics simulation and MM-PBSA binding free energy calculation suggests that diosmin, isoquercetin, rutin and other similar flavone glycosides could serve as SARS-CoV-2 inhibitor, hence an alternative solution to treat COVID-19 upon further clinical validation.

Keywords: COVID-19; Docking screening; Free energy calculation; MD simulation; Natural products; SARS-CoV-2.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antiviral Agents / pharmacology
Biological Products* / pharmacology
COVID-19*
Humans
Molecular Docking Simulation
Pharmaceutical Preparations*
SARS-CoV-2

Substances

Antiviral Agents
Biological Products
Pharmaceutical Preparations