Virtual Screening, Design, Synthesis and Biological Activity of Zika Virus Inhibitors

Abstract

NS5 is a protein component which plays a main role in replication of Zika virus, and its component part-methyl-transferase (5M5B) is the central participants of virus replication and host innate immune response. So it is used as the preferred protein of potential antiviral drugs development. Using 5M5B as receptors and using its binding sites to screen with over 2 million small molecule compounds, the leading compounds of anti-Zika virus were obtained. The structural optimization, activity prediction, chemical synthesis and pharmacological activity of the leading compound were studied. All the synthesized compounds were characterized by 1 H NMR and 13 C NMR. The antiviral activity of compound 3a is better than that of ribavirin (IC 50 =(7.69±0.36) μmol•L -1 for 3a vs IC 50 =(8.15±0.42) μmol•L -1 for ribavirin).