Curcumin as a potential multiple-target inhibitor against SARS-CoV-2 Infection: A detailed interaction study using quantum chemical calculations

Curcumin is one of the important naturally occurring compounds having several medicinal properties such as: antiviral, antioxidant, antifibrotic, antineoplastic as well as anti-inflammatory. SARS-CoV-2 has emerged as inf-ectious virus, which severely infected a large number of people all over the world. Many efforts have been made to prepare novel antiviral compound, but it is still challenging. Naturally occurring compound, curcumin, can be used as an alternative to antiviral compound against SARS-CoV-2. Its effect against SARS-CoV-2 is already highlighted in the literature. But the quantitative study of its interaction with various precursors of SARS-CoV-2 is not reported till date. This paper reports the interaction of curcumin with angiotensin-convert-ing enzyme2, transmembrane serine protease 2, 3-chymotrypsin-like protease and papain-like protease through molecular docking and quantum chemistry calculations to achieve quantitative understanding of underlying interactions. Here the conformational flexibility of curcumin is also highlighted, which helps it to accommodate in the four different docking sites. The study has been performed using calculations of geometrical parameter, atomic charge, electron density, Laplacian of electron density, dipole moment and the energy gap between highest occupied and lowest unoccupied molecular orbitals. The non--covalentinteraction (NCI) analysis is performed to visualize the weak inter-action present in the active sites. Combinedly molecular docking and detailed quantum chemistry calculations revealed that curcumin can be adopted as a potential multiple-target inhibitor against SARS-CoV-2.

Synthesis, characterization, and in silico analysis against SARS CoV-2 of novel benzimidazolium salts

In acute conditions, vaccines are very important, although they provide antibodies for fighting against COVID19 for a certain period. It is necessary to produce an anti-viral agent for a usual healing process against SARS CoV-2 which is responsible the pandemic we are living in. Many drugs with benzimidazole main scaffold are still used in a wide variety of treatment procedures. In this case, substituted benzimidazole structures could be good candidates for fighting against COVID-19. Theoretical calculation methods could be a key tool for overcome the difficulties of individual analyzing of each new structure. In this study, new benzimidazole structures were synthesized and characterized for in silico evaluation as anti-viral agent. The molecules were optimized and analyzed for reactivity with Koopmans Theorem. Also, molecular docking simulations were performed for SARS coronavirus main peptidase (PDB ID: 2GTB), COVID-19 main protease (PDB ID: 5R82), and papain-like protease of SARS CoV-2 (PDB ID: 6W9C) crystals.

Molybdenum Carbonyl Complexes with Benzimidazole Derivatives Against SARS-CoV-2 by Molecular Docking and DFT/TDDFT Methods

Benzimidazole derivative molecules attract attention of scientists due to their bioactivities. The dramatic changes in recorded activities according to the type and position of the substituents motivate synthesis and analysis of new molecules. Commercial benzimidazole-based molecules have been used in therapeutic procedures. It is known that the activities of metal complexes with benzimidazole derivative ligands have different activities when compared to the benzimidazole main structure. Nowadays, one of the most important health problems is COVID-19, which caused the pandemic that we are still experiencing. Although vaccine studies are important to overcome acute problems, regarding the possible post-vaccination adverse effects, the need for new drugs against the virus is obvious. Considering the urgency and the limited facilities during the pandemic, preliminary in silico studies of candidate molecules are essential. In this study, {[bis-(N-benzylbenzimidazole)] tetracarbonylmolybdenum}, {[bis-(N-4-chlorobenzylbenzimidazole)] tetracarbonylmolybdenum} and {[bis-(N-4-methoxybenzylbenzimidazole)] tetracarbonylmolybdenum} were synthesized and characterized. The optimization and the structural analysis of these molecules were performed by DFT/TDDFT methods. The molecules were docked into SARS coronavirus main peptidase (PDB ID: 2gtb), COVID-19 main protease in complex with Z219104216 (PDB ID: 5r82), COVID-19 main protease in complex with an inhibitor N3 (PDB ID: 6lu7) and Papain-like protease of SARS-CoV-2 (PDB ID: 6w9c) crystal structures for evaluation of their anti-viral activity. Molybdenum carbonyl complexes containing benzimidazole derivative ligands have been synthesized, characterized, and analyzed structurally by DFT/TDDFT methods. Antiviral activities of the complexes were analyzed by molecular docking methods against some important Coronavirus targets in parallel with the pandemic period we are living in. Inhibitory potency of the complexes toward COVID-19 targeted is compared to some well-known commercial antivirals.