Virtual screening of antiviral properties of bioactive compounds from liquid smoke against 2A protease of Coxsackievirus-A16

• Main Authors: Cahyati, Miftakhul, Susilo, Agus, Nurjannah, Pranowo, Dodyk, Hermanto, Feri Eko, Primandasari, Elma Putri
• Format: Conference Proceeding
• Language: English
• Subjects: Binding energy; Binding sites; Biocompatibility; Biological activity; Dynamic structural analysis; Molecular docking; Molecular dynamics; Molecular structure; Pharmacology; Protease; Smoke; Structural stability; Substrates; Toxicity
• ISSN: 0094-243X; 1551-7616
• DOI: 10.1063/5.0193867

Hand, foot, and mouth disease (HFMD) is a contagious disease in toddlers and youth, mainly caused by Coxsackievirus-A16 (CA16) infection. On the other hand, liquid smoke (LS) contains numerous bioactive molecules, which improve the value beyond its main application as food seasonings. Although the bioactivity of liquid smoke against mouth disease was reported, its exact mechanism remains inconclusive. Through computational analysis, this research will explore the potential bioactivity of several compounds from LS as an alternative therapeutic agent for HFMD. The investigation started with exploring bioactive compounds for toxicity evaluation using ProTox-II. The passed compounds were then directed for molecular docking against the 2A Protease (2AP) of CA16 to predict their antiviral properties. Compound with specific binding against the catalytic site of 2AP and resemble the binding energy of Benzydamine as the main medications of HFMD, then directed for molecular dynamics analysis. As a result, only 21 compounds of LS have fewer toxicity properties. Molecular docking also discovered that Acetosyringone and Homosyringic Acid had lower binding energy than other pre-screened compounds. Those compounds also interacted with HIS21, TYR89, PRO107, and CYS110 as the substrate-binding site of 2AP. The binding of those compounds to 2AP showed structural stability from the protein atom backbone and ligands structure according to the molecular dynamics simulations. The fluctuations of per-residue were also minimum, and the binding energy remained stable along the simulations. The solvent-accessible surface area (SASA) also displayed a relatively stable conformation at the catalytic cleft position upon binding with the Acetosyringone and Homosyringic Acid compared to Benzydamine. Therefore, the protective effect of LS against HFMD may occur through antiviral activity against CA16 by inhibition of viral replications.