Tomato Chlorosis Virus Minor Coat Protein as a Novel Target To Screen Antiviral Drugs.

Minor coat protein (mCP), an important component of tomato chlorosis virus (ToCV), plays a significant role in the process of virus assembly and movement and is directly related to the virus-insect transmission. Therefore, ToCV mCP could be considered as a potent target for anti-ToCV drugs. In this study, ToCV mCP was first cloned, expressed, purified, and a novel target to screen the antiviral agents. The results showed that some antiviral compounds bound to ToCV mCP with strongly affinities in vitro, including quinazoline derivatives 4a and 4b, Ningnanmycin, and Ribavirin. Subsequently, three-dimensional-quantitative structure-activity relationship (3D-QSAR) analysis was performed based on the binding affinities, and the model indicated that 4a and 4b had indeed stronger binding effects on ToCV mCP than other quinazoline derivatives. Finally, the anti-ToCV activities of compounds 4a and 4b were evaluated by quantitative real-time polymerase chain reaction in vivo. Compounds 4a and 4b inhibited infection of ToCV in the host and as well as reduced the level of ToCV mCP gene expression. Thus, ToCV mCP can be used as a novel drug target for screening anti-ToCV agents, and the ligand-based 3D-QSAR analysis of quinazoline derivatives provided new insights into the design and optimization of novel anti-ToCV drug molecules based on ToCV mCP.