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Identification of Polyphenol Derivatives as Novel SARS-CoV-2 and DENV Non-Nucleoside RdRp Inhibitors.

Shenghua GaoLetian SongHongtao XuAntonios FikatasMerel OeyenSteven De JongheFabao ZhaoLanlan JingDirk JochmansLaura VangeelYusen ChengDongwei KangJohan NeytsPiet HerdwijnDominique ScholsPeng ZhanXinyong Liu
Published in: Molecules (Basel, Switzerland) (2022)
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 Mg 2+ 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.
Keyphrases
  • sars cov
  • dengue virus
  • respiratory syndrome coronavirus
  • coronavirus disease
  • public health
  • zika virus
  • machine learning
  • molecular docking
  • deep learning
  • dna binding
  • molecular dynamics simulations