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.
Funder
Shandong Provincial Key research and development project
Science Foundation for Outstanding Young Scholars of Shandong Province
Foreign cultural and educational experts Project
Guangdong Basic and Applied Basic Research Foundation
China Postdoctoral Science Foundation
Shandong Province Natural Science Foundation for Youths
Natural Science Foundation of China
Subject
Chemistry (miscellaneous),Analytical Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Molecular Medicine,Drug Discovery,Pharmaceutical Science
Cited by
4 articles.
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