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

Abstract

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.

Effect of Flutriafol Exposure on Residue Characteristics in Pig Muscle and Fat Tissue

“…It is a chiral triazole fungicide employed to control plant pathogens. The fungicidal mechanism of such pesticides inhibits ergosterol biosynthesis and cell wall synthesis ( Song et al, 2019 ; Yang et al, 2020 ).…”

Synthesis, Anti-Tomato Spotted Wilt Virus Activities, and Interaction Mechanisms of Novel Dithioacetal Derivatives Containing a 4(3H)-Quinazolinone Pyrimidine Ring

“…In addition, in our follow-up studies, we gradually found that dithioacetal derivatives showed good biological activities against a variety of plant viruses, such as the common plant viruses TMV, 24 potato virus Y, 25 CMV, 26 and ToCV. 27,28 At the same time, we found that pyrimidine derivatives present good fungicidal, 29 insecticidal, 30 herbicidal, 31 and bactericidal 32 activities. However, the biological activities of 4(3H)-quinazolinone derivatives, dithioacetal derivatives, or pyrimidine derivatives against TSWV have not been reported.…”

“…Then, on the basis of q 2 and ONC, the CoMFA and CoMSIA models were obtained through noncross validation, and the Fisher-statistic values ( F ), noncross-validation coefficient ( r 2 ), and standard error of the estimate (SEE) were obtained. According to the existing method, the external predictive correlation coefficient ( Q 2 F1 , Q 2 F2 ) and concordance correlation coefficient (CCC) of the models were calculated. ,− …”

Review on Structures of Pesticide Targets

“…For example, harpin binding protein-1 is a potential target activated antiviral response in tobacco by antiviral agent dufulin [ 81 ], and tomato chlorosis virus (ToCV), CP play significant roles in sustaining the methyl cycle and S-adenosylmethionine-dependent methyltransferase activity and its minor CP play important roles in silencing suppression activity to counteract the RNA silencing-mediated defense response of the host [ 82 , 83 ]. Glucopyranoside derivatives, pyrimidine derivatives, 4(3H)-quinazolinone derivatives, and novel quinazolinone sulfide inhibitors targets ToCV coat protein with high anti-ToCV activity [ 84 , 85 , 86 , 87 ], and its minor coat protein is regarded as a novel target for the new green anti-ToCV inhibitors [ 88 ].…”