Sains Malaysiana 50(5)(2021): 1473-1483

http://doi.org/10.17576/jsm-2021-5005-26

Molecular Docking Unveils Prospective Inhibitors for the SARS-COV-2 Main Protease

(Mengedok Molekul Mendedahkan Prospektif Perencat untukProtease Utama SARS-COV-2)

FAWAD AHMAD¹, SAIMA IKRAM¹, JAMSHAID AHMAD¹*, IRSHAD UR REHMAN¹, SAEED ULLAH KHATTAK¹, SADIA BUTT² & MARYAM MUSHTAQ³

¹Centre of Biotechnology & Microbiology, University of Peshawar, Peshawar, Pakistan

²Shaheed Benazir Bhutto Women University, Peshawar, Pakistan

³Northwest General Hospital & Research Center, Peshawar, Pakistan

Received: 16 January 2021/Accepted: 17 March 2021

ABSTRACT

The recent emergence of a novel coronavirus strain (SARS-CoV-2) has stimulated global efforts to identify potential drugs that target proteins expressed by this novel coronavirus. Among these, the main protease of SARS-CoV-2 (3CL-protease (3CL^Pro), also known as (M^Pro) is one of the best choices for the scientists to target. 3CL^Pro is involved in the processing of polyproteins into mature non-structural viral proteins. An X-ray crystallographic structure (PDB ID 6LU7) of this protein was obtained from the PDB database. ChemDiv libraries of ~80,000 antiviral and ~13,000 coronavirus-targeting molecules were screened against the 3D structure of 3CL^Pro of SARS-CoV-2. We have identified a panel of molecules that showed an activity and potentially block the active site of the SARS-CoV-2 main protease. These molecules can be investigated further to develop effective virus-inhibiting molecules to treat this highly distressing disease, causing extreme unrest across the globe.

Keywords: Antivirals; coronavirus library; COVID-19; SARS-CoV-2; virtual screening

ABSTRAK

Kemunculan strain koronavirus baru-baru ini (SARS-CoV-2) telah mendorong usaha global untuk mengenal pasti ubat berpotensi yang mensasarkan protein yang diekspres oleh novel koronavirus ini. Antaranya, protease utama SARS-CoV-2 (3CL-protease (3CL^Pro), juga dikenali sebagai (M^Pro) adalah salah satu pilihan terbaik untuk disasarkan oleh para saintis. 3CL^Pro terlibat dalam pemprosesan poliprotein kepada virus protein matang tak-berstruktur. Struktur kristalografi sinar-X (PDB ID 6LU7) protein ini diperoleh dari pangkalan data PDB. Perpustakaan ChemDiv dengan ~80,000 antivirus dan ~13,000 molekul penyasaran koronavirus disaring terhadap struktur 3D 3CL^Pro SARS-CoV -2. Kami telah mengenal pasti panel molekul yang menunjukkan aktiviti dan berpotensi menyekat tapak aktif protease utama SARS-CoV-2. Molekul ini boleh dikaji lebih lanjut untuk mengembangkan molekul perencatan-virus yang berkesan untuk merawat penyakit yang menyebabkan keresahan melampau di seluruh dunia ini.

Kata kunci: Antivirus; COVID-19; perpustakaan koronavirus; saringan maya; SARS-CoV-2

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*Corresponding author; email: jamshaidbiotech@yahoo.com