In vivo antiviral activity and disassembly mechanism of novel 1-phenyl-5-amine-4-pyrazole thioether derivatives against Tobacco mosaic virus.

A series of novel 1-phenyl-5-amine-4-pyrazole thioether derivatives containing a 1,3,4-oxadiazole moiety was designed and synthesised. In vivo antiviral bioassay results showed that most of the target compounds exhibited excellent inactivation activity against Tobacco mosaic virus (TMV). The EC values of the inactivation activities for T, T, T, T, T and T were 15.7, 15.7, 15.5, 11.9, 12.5 and 16.5 μg/mL, respectively, which were remarkably superior over that of the commercialised antiviral agent ningnanmycin (40.3 μg/mL). Morphological study using AFM and TEM of TMV treated with T showed that T could significantly shorten the polymerization length of TMV particles and formed a distinct break on the rod-shaped TMV. Investigations for virus infection efficiency on tobacco leaves demonstrated that infectivity of virion had been reduced obviously upon T treatment. Subsequently, a strong interaction between T and TMV-CP (K = 3.8 μM, score 6.11) was observed through MST experiments. Molecular docking study further revealed that target compounds interact with amino acid residue Glu50 in TMV CP, causing disassembly of virion, shorting the length of the virion and reducing the infectivity of virion, and resulting in high inactivating activity of target compounds. This study provides a new insight for discovery of antiviral compounds through a new action mechanism with a new binding site.