In Silico Discovery of Natural Products Against Dengue RNA-Dependent RNA Polymerase Drug Target

[摘要] The viral infection caused by the dengue virus (DENV) is one of the most challenging diseases in the tropical regions of the world. The absence of drugs for dengue to this date calls for intense efforts to discover and develop the much coveted therapeutics for this mosquito-borne disease. One of the most attractive antiviral targets is the DENV RNAdependent RNA polymerase (RdRp), which catalyzes the de novo initiation as well as elongation of the flavivirus RNA genome. In this work, almost 5000 natural products were docked to DENV RdRp. The top 197 molecules with greater binding energies than the known ligand of the target were further clustered down to furnish 35 classes of molecular structures. These compounds with satisfactory predicted drug properties and with known natural origin can be further explored to pave the way for the first anti-dengue drug.

[学科分类] 生物化学/生物物理

[关键词] Dengue virus (DENV);RNA-dependent RNA polymerase (RdRp);molecular docking;in silico ADMET;natural products