In Silico Analysis Using SARS-CoV-2 Main Protease and a Set of Phytocompounds to Accelerate the Development of Therapeutic Components against COVID-19

Abstract

SARS-CoV-2, the virus that caused the widespread COVID-19 pandemic, is homologous to SARS-CoV. It would be ideal to develop antivirals effective against SARS-CoV-2. In this study, we chose one therapeutic target known as the main protease (Mpro) of SARS-CoV-2. A crystal structure (Id: 6LU7) from the protein data bank (PDB) was used to accomplish the screening and docking studies. A set of phytocompounds was used for the docking investigation. The nature of the interaction and the interacting residues indicated the molecular properties that are essential for significant affinity. Six compounds were selected, based on the docking as well as the MM-GBSA score. Pentagalloylglucose, Shephagenin, Isoacteoside, Isoquercitrin, Kappa-Carrageenan, and Dolabellin are the six compounds with the lowest binding energies (−12 to −8 kcal/mol) and show significant interactions with the target Mpro protein. The MMGBSA scores of these compounds are highly promising, and they should be investigated to determine their potential as Mpro inhibitors, beneficial for COVID-19 treatment. In this study, we highlight the crucial role of in silico technologies in the search for novel therapeutic components. Computational biology, combined with structural biology, makes drug discovery studies more rigorous and reliable, and it creates a scenario where researchers can use existing drug components to discover new roles as modulators or inhibitors for various therapeutic targets. This study demonstrated that computational analyses can yield promising findings in the search for potential drug components. This work demonstrated the significance of increasing in silico and wetlab research to generate improved structure-based medicines.

In-silico investigation on the discovery of synthesized nucleoside-based antivirals against monkeypox and SARS-CoV-2 Virus

“…The proposed modification has the potential to induce changes in the steric properties, electronic surroundings, and hydrogen bonding interactions that occur between the binding site of the enzyme and the nucleoside analogue. We employed the utilization of C-7.8 was initially prepared and subsequently underwent positional alteration using fluorine, [22], [24], [26], [46], [47], [48]]. While in silico analyses produce a lot of data, wetlab experiments are a necessary part in finding the best lead compounds [46].…”

“…We employed the utilization of C-7.8 was initially prepared and subsequently underwent positional alteration using fluorine, [22], [24], [26], [46], [47], [48]]. While in silico analyses produce a lot of data, wetlab experiments are a necessary part in finding the best lead compounds [46]. Structural biology makes bioinformatics more straightforward [49].…”

“…The primary targets for the main protease of SARS-CoV-2 Mpro (PDB ID: 6LU7) and A42R Profilinlike protein (PDB ID: 4QWO) were retrieved from PDB. The major coronavirus enzyme, SARS-CoV-2 Mpro, is described in the literature as being essential for viral transcription and replication, making it a prospective therapeutic target [ [22], [23], [46]]. The A42R Profilin-like protein of monkeypox virus has also been studied recently due to their role in assembly [ [5], [25], [47]].…”

“…A grid must be established before ligand docking is feasible [22]. For receptor grid development, a built protein structure with the proper bond orders and charges is needed [46]. The receptor grid generation was followed by the docking of the receptors with prepared ligands using Glide of the Schrodinger suite [26].…”

“…In 7-amino G and 8-Iodo G, the H-bond interactions are found between the amine and hydroxyl groups with the amino acid residues of Glu 166, Asn 142 and Phe with individual ligands and 6LU7 in all the cases were H-bonds and salt bridges. In the study conducted by Mustafa et al [46] on identifying the potential therapeutic phytocompounds against Mpro of SARS-CoV-2, key residues namely Glu166, Gln189, and Thr190 were found to have major role in the interaction. Similarly, co-crystallized peptide inhibitors such as N3 were found to interact with residues Thr190, Gln189, Glu166, His164, Phe140, and Gly143 through hydrogen bonds in 6LU7 [55].…”