Reckoning γ-Glutamyl-S-allylcysteine as a potential main protease (m^pro) inhibitor of novel SARS-CoV-2 virus identified using docking and molecular dynamics simulation

Abstract

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2 or COVID-19), outbreak was first reported in December 2019 in the Wuhan, China. COVID-19 managed to spread worldwide and so far more than 9.1 million cases and more than 4.7 lakh death has been reported globally. Children, pregnant women, elderly population, immunocompromised patients, and patients with conditions like asthma, diabetes, etc. are highly vulnerable to COVID infection. Currently, there is no treatment available for COVID-19 infection. Traditional medicinal plants have provided bioactive molecules in the past that are efficiently used during conditions like cancer, malaria, microbial infections, immune-compromised states, etc. AYUSH India has recommended the use of Curcuma longa, Allium sativum, Ocimum tenuiflorum , and Withania somnifera for immune-boosting during SARS-CoV-2 infection. In the present study, we investigated the potential of 63-major bioactive molecules of these plants against SARS-CoV-2 main protease (M pro ) through docking studies and compared the results with known inhibitor 11a. Our results proposed cuscohygrine, γ-Glutamyl-S-allylcysteine, anahygrine, and S-allylcystein as the potent inhibitors against M pro identified using molecular docking and molecular simulation dynamics. Interestingly, these molecules are from A. sativum , and W. somnifera , which are known for their antimicrobial and immunomodulatory potential. None of the proposed molecules have earlier been reported as antiviral molecules. Our results predict very strong potential of these four-molecules against SARS-CoV-2 M pro , especially γ-glutamyl-S-allylcysteine, as all four form hydrogen bonding with Glu166 that is a crucial residue for the formation of the biologically active dimeric form of M pro . Therefore, we strongly recommend further research on these biomolecules against SARS-CoV-2.

Potential Inhibitors of Monkeypox Virus Revealed by Molecular Modeling Approach to Viral DNA Topoisomerase I

“…RMSF discloses the elasticity of diverse sites of protein–ligand complexes [ 19 , 20 ]. The stability profile analysis was utilized to assess residues dedicated to the complex structural undulation.…”

Targeting SARS-CoV-2 main protease by teicoplanin: A mechanistic insight by docking, MM/GBSA and molecular dynamics simulation

“… S.No. Compound a MM/GBSA binding energies (Kcal/mol) References 1 Lithospermic acid B −118.7 [49] 2 Ritonavir −107.6 [50] 3 AT1001 −106.3 [53] 4 GHRP-2 –106.0 [54] 5 Rutin −99.8 [51] 6 N3 −80.0 [55] 7 ChemDiv_D658-0159 −77.5 [56] 8 Amikacin −73.8 [52] 9 γ-glutamyl-S-allylcysteine −72.5 [57] 10 ZINC000003947429 −70.4 [58] 11 PubChem-129-716-607 −69.0 [59] 12 11b −65.6 [60] a Compound name has been kept same as reported in respective literature. …”

ADMET profiling and molecular docking of potential antimicrobial peptides previously isolated from African catfish, Clarias gariepinus

“…The BBB score depicts the capability of a molecule to penetrate the semipermeable blood-brain barrier that guards the CNS against potentially harmful substances. All the fish-derived antimicrobial peptides studied had a BBB score below the threshold (BBB score <0.1) unlike amyloid beta (Aβ) peptides ( Tran et al, 2019 ) and chloroquine ( Parashar et al, 2021 ). This finding implies the peptides are unable to cross the BBB, signifying potential safety to the CNS.…”