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

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.

Novel analogues of a nonnucleoside SARS-CoV-2 RdRp inhibitor as potential antivirotics

“…Recently, many studies have been focusing on drug repurposing or screening libraries of already approved biologically active compounds [ 16 – 17 ]. This approach might represent a very promising strategy in the case of targeting the coronaviral RdRp due to the highly conserved structure of the polymerase, not only across the CoV group but also in other RNA viruses [ 13 ]. A great example of this phenomenon is remdesivir, which was originally developed as a therapeutic agent against Ebola virus [ 18 – 19 ].…”

“…Since the beginning of the pandemic, a variety of heterocyclic small molecules -either of natural or synthetic origin -was reported as promising inhibitors of the SARS-CoV-2 RdRp [13][14][15]. However, compounds with a sufficient combination of high potency and suitable pharmacokinetic properties are still scarce.…”

Synthesis of Isolated DNA Aptamer and Its Application of AC-Electrothermal Flow-Based Rapid Biosensor for the Detection of Dengue Virus in a Spiked Sample

“…Currently, there is no approved antiviral agent or vaccine for dengue fever; however, treatment-oriented medical methods are being used to develop potential agents against DENV . Furthermore, an increase in the number of SARS-CoV-2 and dengue virus co-infection cases has been reported in dengue-endemic areas. − Cases of co-infection are of great concern as the risk of infection with two viruses is significantly higher than that of a single virus, and the threat of coronavirus is still prominent. , Therefore, it is essential that a method is developed that can detect DENV in the early stages and prevent the advancement of the disease.…”

“…8−10 Cases of co-infection are of great concern as the risk of infection with two viruses is significantly higher than that of a single virus, and the threat of coronavirus is still prominent. 11,12 Therefore, it is essential that a method is developed that can detect DENV in the early stages and prevent the advancement of the disease.…”