Discovery of Novel Chromone Derivatives as Potential Anti-TSWV Agents

A series of novel chromone derivatives containing dithioacetals were prepared, and their antiviral activity against tomato spotted wilt virus (TSWV) was studied. The results showed that compounds A1-A31 had good inhibitory activity against TSWV. The 3D-QSAR model was built to analyze the structure-activity relationship of the compounds. We further found that compounds A32 and A33 had excellent anti-TSWV activities based on the results of 3D-QSAR, which were better than the control agents ningnanmycin and ribavirin. To study the mode of action of these compounds on TSWV, the nucleocapsid protein of TSWV (TSWV N) was cloned, expressed, and purified in the study. The results of the microscale thermophoresis (MST) experiments indicate that compound A33 can better bind with TSWV N. The molecular docking experiment further indicated that the mode of action of the compound A33 is to inhibit the virus by blocking the combination of TSWV N and viral RNA. Therefore, this study has found that chromone compound A33 is a potential anti-TSWV agent that targets TSWV N.