Leena H. Bajrai, Arwa A. Faizo, Areej A. Alkhaldy, Vivek Dhar Dwivedi, Esam I. Azhar
A therapy for COVID-19 (Coronavirus Disease 19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) remains elusive due to the lack of an effective antiviral therapeutic molecule. The SARS-CoV-2 main protease (Mpro), which plays a vital role in the viral life cycle, is one of the most studied and validated drug targets.
Pharmaceutical research into the discovery and development of therapeutic compounds has expanded rapidly since the emergence of COVID-19 (a disease caused by SARS-CoV-2 infection). Target-based drug discovery has been investigated exponentially due to the release of experimental structures of essential structural and non-structural proteins of SARS-CoV-2.
Materials and Methods:
The protein structure of SARS-CoV-2 Mpro was sourced from the protein data bank (PDB)  with PDB ID: 6W63 (https://www.rcsb.org/structure/6W63). This structure contains the SARS-CoV-2 main protease solved using the X-ray diffraction technique at 2.10 Å resolution.
This study primarily depends on the structure-based virtual screening (SBVS), where the receptor structure (PDB ID: 6W63) was prepared for docking using the protein preparation wizard of the Schrödinger suite.
This work demonstrates the structure-based screening of anti-dengue drugs against the SARS-CoV-2 Mpro. In SARS-CoV-2, the main protease (Mpro) is responsible for the maturation of polyprotein, which is essential for the virus’s proliferation . In addition, Mpro also plays a role in the proteolytic processing of enzymes required for the replication of SARS-CoV-2.
Acknowledgments: The authors are highly thankful to Dr. Amaresh Kumar Sahoo, Indian Institute of Information Technology, Prayagraj, India for providing his kind support for giving access to Schrödinger suite (Virtual screening workflow & MMGSA).
Citation: Bajrai LH, Faizo AA, Alkhaldy AA, Dwivedi VD, Azhar EI (2022) Repositioning of anti-dengue compounds against SARS-CoV-2 as viral polyprotein processing inhibitor. PLoS ONE 17(11): e0277328. https://doi.org/10.1371/journal.pone.0277328
Editor: Chandrabose Selvaraj, Alagappa University, INDIA
Received: June 14, 2022; Accepted: October 24, 2022; Published: November 16, 2022.
Copyright: © 2022 Bajrai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the paper and its Supporting information files.
Funding: This project was funded by the Deanship of Scientific Research (DSR) at King Abdulaziz University, Jeddah, under grant number: GCV19-46-1441. The authors therefore acknowledge with thanks DSR for technical and financial support.
Competing interests: The authors have declared that no competing interests exist.