Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Physical Sciences, Biochemistry & Molecular Biology, Chemistry, Multidisciplinary, Chemistry, SARS-CoV-2, DENV, polyphenol, RdRp, non-nucleoside, DENGUE VIRUS, ACCURATE DOCKING, POLYMERASE, MODELS, TARGET, GLIDE, Humans, COVID-19, Polyphenols, RNA-Dependent RNA Polymerase, Antiviral Agents, Molecular Docking Simulation, 0304 Medicinal and Biomolecular Chemistry, 0305 Organic Chemistry, 0307 Theoretical and Computational Chemistry, Organic Chemistry, 3404 Medicinal and biomolecular chemistry, 3405 Organic chemistry

Abstract:

The Coronavirus Disease 2019 (COVID-19) and dengue fever (DF) pandemics both remain to be significant public health concerns in the foreseeable future. Anti-SARS-CoV-2 drugs and vaccines are both indispensable to eliminate the epidemic situation. Here, two piperazine-based polyphenol derivatives DF-47 and DF-51 were identified as potential inhibitors directly blocking the active site of SARS-CoV-2 and DENV RdRp. Data through RdRp inhibition screening of an in-house library and in vitro antiviral study selected DF-47 and DF-51 as effective inhibitors of SARS-CoV-2/DENV polymerase. Moreover, in silico simulation revealed stable binding modes between the DF-47/DF-51 and SARS-CoV-2/DENV RdRp, respectively, including chelating with Mg2+ near polymerase active site. This work discovered the inhibitory effect of two polyphenols on distinct viral RdRp, which are expected to be developed into broad-spectrum, non-nucleoside RdRp inhibitors with new scaffold.