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Elucidation of the antiviral mechanism of natural therapeutic molecules Herbacetin and Caffeic acid phenethyl ester against Chikungunya and Dengue virus

Bhutkar, M.; Rani, R.; Kothiala, A.; Mahajan, S.; Waghmode, B.; Kumar, R.; Singh, V.; Sircar, D.; Kumar, P.; Tomar, S.

2022-05-31 microbiology
10.1101/2022.05.31.494145 bioRxiv
Show abstract

Chikungunya (CHIKV) and dengue (DENV) viruses pose a public health risk and lack antiviral treatment. Structure-based virtual screening of natural MTase substrates library identified herbacetin (HC) and caffeic acid phenethyl ester (CAPE) as potential CHIKV nsP1 and DENV NS5 MTase inhibitors. Binding affinities and MTase inhibition were confirmed using purified proteins. Crystal structure of DENV3 NS5 MTase and CAPE complex revealed CAPE binding at GTP and cap 0 RNA sites. Interestingly, HC and CAPE depleted polyamines, which are crucial for RNA virus replication, and effectively diminished replication with IC50 values of [~]13.44 {micro}M and [~]0.57 {micro}M against CHIKV, and [~]7.24 {micro}M and [~]1.01 {micro}M against DENV, respectively. Polyamine addition did not reverse the antiviral effects, suggesting a dual inhibition mechanism. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=110 SRC="FIGDIR/small/494145v5_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@1f579eforg.highwire.dtl.DTLVardef@11862eborg.highwire.dtl.DTLVardef@67276org.highwire.dtl.DTLVardef@144c7f8_HPS_FORMAT_FIGEXP M_FIG C_FIG

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"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.