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.