First Report on Anti-TSWV Activities of Quinazolinone Derivatives Containing a Dithioacetal Moiety.

Tomato spotted wilt virus (TSWV) is a plant virus with strong infectivity and destructive power. Given the lack of effective control agents, TSWV causes significant economic damage to several vegetables and ornamental plants worldwide. In this study, we designed and synthesized a series of novel quinazolinone derivatives containing a dithioacetal moiety and evaluated their antiviral activity in vitro and in vivo against TSWV. Some candidate compounds showed good anti-TSWV activity. Compound 6n shows excellent anti-TSWV activity in vivo, and the EC50 value is 188 mg/L, which is notably better than that observed for ribavirin (642 mg/L), xiangcaoliusuobingmi (420 mg/L), and ningnanmycin (257 mg/L). In addition, compound 6n interacts with TSWV coat protein at sites ARG94 and ARG95 forming four π-alkyl interactions. Compound 6n (9.4 µM) shows a better binding affinity with TSWV coat protein than ribavirin (67.8 µM), xiangcaoliusuobingmi (33.8 µM), and ningnanmycin (24.3 µM). Therefore, compound 6n can serve as a lead compound for the discovery of new antiviral agents for the management of TSWV.