Antiviral Activity of an Indole-Type Compound Derived from Natural Products, Identified by Virtual Screening by Interaction on Dengue Virus NS5 Protein

Abstract

Dengue is an acute febrile illness caused by the Dengue virus (DENV), with a high number of cases worldwide. There is no available treatment that directly affects the virus or the viral cycle. The objective of this study was to identify a compound derived from natural products that interacts with the NS5 protein of the dengue virus through virtual screening and evaluate its in vitro antiviral effect on DENV-2. Molecular docking was performed on NS5 using AutoDock Vina software, and compounds with physicochemical and pharmacological properties of interest were selected. The preliminary antiviral effect was evaluated by the expression of the NS1 protein. The effect on viral genome replication and/or translation was determined by NS5 production using DENV-2 Huh-7 replicon through ELISA and viral RNA quantification using RT-qPCR. The in silico strategy proved effective in finding a compound (M78) with an indole-like structure and with an effect on the replication cycle of DENV-2. Treatment at 50 µM reduced the expression of the NS5 protein by 70% and decreased viral RNA by 1.7 times. M78 is involved in the replication and/or translation of the viral genome.

Novel Antiviral Agents: Synthesis, Molecular Modelling Studies and Biological Investigation

“…Compound M78 tested at a concentration of 50 µM reduced viral RNA (1.7 times), whereas NS5 protein expression was reduced by 70%, indicating that the replication and/or translation of the viral genome is strongly influenced by M78. Accordingly, studies of M78 function in NS5, pre-treatment activity, and virucidal effects on additional Dengue serotypes and flaviviruses are highly desired [ 7 ].…”