Unravelling lead antiviral phytochemicals for the inhibition of SARS-CoV-2 M pro enzyme through in silico approach

• Published in: Life sciences (1973) Vol. 255; p. 117831
• Main Authors: Gurung, Arun Bahadur, Ali, Mohammad Ajmal, Lee, Joongku, Farah, Mohammad Abul, Al-Anazi, Khalid Mashay
• Format: Journal Article
• Language: English
• Published: Netherlands 15.08.2020
• Subjects: Amino Acid Sequence; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; Betacoronavirus - drug effects; Betacoronavirus - enzymology; Betacoronavirus - metabolism; Binding Sites; Computer Simulation; Coronavirus 3C Proteases; Coronavirus Infections - drug therapy; Coronavirus Infections - epidemiology; Coronavirus Infections - virology; COVID-19; Cysteine Endopeptidases - chemistry; Cysteine Endopeptidases - metabolism; Drug Evaluation, Preclinical - methods; Humans; Molecular Docking Simulation; Pandemics; Plant Extracts - pharmacology; Pneumonia, Viral - drug therapy; Pneumonia, Viral - epidemiology; Pneumonia, Viral - virology; Protease Inhibitors - chemistry; Protein Binding; SARS-CoV-2; Small Molecule Libraries - pharmacology; Viral Nonstructural Proteins - antagonists & inhibitors; Viral Nonstructural Proteins - chemistry; Viral Nonstructural Proteins - metabolism; Virus Replication - drug effects; COVID-19; Medicinal plants; SARS-CoV-2; Phytochemicals; Antiviral properties; SARS-CoV-2 M(pro); Binding affinity; Molecular docking
• ISSN: 1879-0631
• DOI: 10.1016/j.lfs.2020.117831

A new SARS coronavirus (SARS-CoV-2) belonging to the genus Betacoronavirus has caused a pandemic known as COVID-19. Among coronaviruses, the main protease (M ) is an essential drug target which, along with papain-like proteases catalyzes the processing of polyproteins translated from viral RNA and recognizes specific cleavage sites. There are no human proteases with similar cleavage specificity and therefore, inhibitors are highly likely to be nontoxic. Therefore, targeting the SARS-CoV-2 M enzyme with small molecules can block viral replication. The present study is aimed at the identification of promising lead molecules for SARS-CoV-2 M enzyme through virtual screening of antiviral compounds from plants. The binding affinity of selected small drug-like molecules to SARS-CoV-2 M , SARS-CoV M and MERS-CoV M were studied using molecular docking. Bonducellpin D was identified as the best lead molecule which shows higher binding affinity (-9.28 kcal/mol) as compared to the control (-8.24 kcal/mol). The molecular binding was stabilized through four hydrogen bonds with Glu166 and Thr190 as well as hydrophobic interactions via eight residues. The SARS-CoV-2 M shows identities of 96.08% and 50.65% to that of SARS-CoV M and MERS-CoV M respectively at the sequence level. At the structural level, the root mean square deviation (RMSD) between SARS-CoV-2 M and SARS-CoV M was found to be 0.517 Å and 0.817 Å between SARS-CoV-2 M and MERS-CoV M . Bonducellpin D exhibited broad-spectrum inhibition potential against SARS-CoV M and MERS-CoV M and therefore is a promising drug candidate, which needs further validations through in vitro and in vivo studies.