Drug repurposing for coronavirus (COVID-19): in silico screening of known drugs against coronavirus 3CL hydrolase and protease enzymes

Loading...
Thumbnail Image

Date

2020

Authors

Al-Obaidi, Anas
Sahin, Alp Tegin
Yelekçi, Kemal

Journal Title

Journal ISSN

Volume Title

Publisher

TAYLOR & FRANCIS LTD

Research Projects

Organizational Units

Journal Issue

Abstract

In December 2019, COVID-19 epidemic was described in Wuhan, China, and the infection has spread widely affecting hundreds of thousands. Herein, an effort was made to identify commercially available drugs in order to repurpose them against coronavirus by the means of structure-based virtual screening. In addition, ZINC15 library was used to identify novel leads against main proteases. Human TMPRSS2 3D structure was first generated using homology modeling approach. Our molecular docking study showed four potential inhibitors against Mpro enzyme, two available drugs (Talampicillin and Lurasidone) and two novel drug-like compounds (ZINC000000702323 and ZINC000012481889). Moreover, four promising inhibitors were identified against TMPRSS2; Rubitecan and Loprazolam drugs, and compounds ZINC000015988935 and ZINC000103558522. ADMET profile showed that the hits from our study are safe and drug-like compounds. Furthermore, molecular dynamic (MD) simulation and binding free energy calculation using the MM-PBSA method was performed to calculate the interaction energy of the top-ranked drugs. Communicated by Ramaswamy H. Sarma Keywords

Description

Keywords

SPIKE PROTEIN, INHIBITORS, COVID-19, structure-based virtual screening, Homology modeling, ADMET, MD simulation, MM-PBSA

Turkish CoHE Thesis Center URL

Citation

223

WoS Q

N/A

Scopus Q

Q2

Source

Volume

Issue

Start Page

End Page