Rational design of phytovirucide inhibiting nucleocapsid protein aggregation in tomato spotted wilt virus

Ineffectiveness of managing plant viruses by chemicals has posed serious challenges in crop production. Recently, phase separation has shown to play a key role in viral lifecycle. Using inhibitors that can disturb biomolecular condensates formed by phase separation for virus control has been reported in medical field. However, the applicability of this promising antiviral tactic for plant protection has not been explored. Here, we report an inhibitor, Z9, that targets the tomato spotted wilt virus (TSWV) N protein. Z9 is capable of interacting with the amino acids in the nucleic acid binding region of TSWV N, disrupting the assembly of N and RNA into phase-separated condensates, the reduction of which is detrimental to the stability of the N protein. This study provides a strategy for phase separation-based plant virus control.