Abstract
Benzalacetophenones, precursors of flavonoids are aromatic ketones and enones and possess the immunostimulant as well as antiviral activities. Thus, benzalacetophenones were screened against the COVID-19 that could be lethal in patients with compromised immunity. We considered ChEBI recorded benzalacetophenone derivative(s) and evaluated their activity against 3C-like protease (3CL pro ), papain-like protease (PL pro ), and spike protein of SARS-Cov-2 to elucidate their possible role as antiviral agents. The probable targets for each compound were retrieved from DIGEP-Pred at 0.5 pharmacological activity and all the modulated proteins were enriched to identify the probably regulated pathways, biological processes, cellular components, and molecular functions. In addition, molecular docking was performed using AutoDock 4 and the best-identified hits were subjected to all-atom molecular dynamics simulation and binding energy calculations using molecular mechanics Poisson-Boltzmann surface area (MMPBSA). The compound 4-hydroxycordoin showed the highest druglikeness score and regulated nine proteins of which five were down-regulated and four were upregulated. Similarly, enrichment analysis identified the modulation of multiple pathways concerned with the immune system as well as pathways related to infectious and non-infectious diseases. Likewise, 3′-(3-methyl-2-butenyl)-4′-O-β-d-glucopyranosyl-4,2′-dihydroxychalcone with 3CL pro , 4-hydroxycordoin with PL pro and mallotophilippen D with spike protein receptor-binding domain showed highest binding affinity, revealed stable interactions during the simulation, and scored binding free energy of -26.09 kcal/mol, -16.28 kcal/mol, and -39.2 kcal/mol, respectively. Predicted anti-SARS-CoV-2 activities of the benzalacetophenones reflected the requirement of wet lab studies to develop novel antiviral candidates.
Keywords: 3CL(pro); Benzalacetophenones; COVID-19; Immune boost; Network pharmacology; PL(pro); Spike protein.
【저자키워드】 COVID-19, network pharmacology, spike protein., 3CL(pro), Benzalacetophenones, Immune boost, PL(pro), 【초록키워드】 Diseases, Immunity, Antiviral, spike, molecular docking, flavonoids, 3CL pro, molecular dynamics, immune system, protease, binding free energy, binding affinity, Spike protein, binding energy, Molecular dynamics simulation, free energy, Papain-like protease, Protein, Simulation, Antiviral agents, Patient, pathway, target, network, molecular, enrichment analysis, Molecular mechanics, Immune boost, AutoDock, Interaction, Anti-SARS-CoV-2 Activity, Pathways, antiviral activities, surface area, Candidates, biological processes, modulation, highest binding affinity, Compound, domain, precursors, Papain, precursor, multiple pathways, non-infectious, cellular components, molecular functions, pharmacological, lab, FIVE, immunostimulant, highest, identify, develop, addition, evaluated, nine, was performed, screened, reflected, regulated, upregulated, recorded, down-regulated, modulated, multiple pathway, retrieved, scored, 【제목키워드】 SARS-CoV-2, derivative,