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

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 27, 2025

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

Language: Английский

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Cucumber mosaic virus 2b directs fibrillarin translocation to plasmodesmata to promote viral movement

New Phytologist, Journal Year: 2025, Volume and Issue: unknown

Published: March 3, 2025

Language: Английский

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Carbene-catalyzed Phthalide Ether Functionalization for Discovering Chiral Phytovirucides that Specifically Targets Viral Nia Protein to Inhibit Proliferation

Research, Journal Year: 2025, Volume and Issue: 8

Published: Jan. 1, 2025

Plant diseases caused by vegetable viruses are an important threat to global food security, presenting a major challenge for the development of antiviral agrochemicals. Functional proteins plant play crucial role in viral life cycle, and targeted inhibition these has emerged as promising strategy. However, current discovery small molecules is hampered limitations synthetic approaches narrow range targets. Herein, we report practical application organocatalysis serving pesticide that bears unique molecular basis. An N -heterocyclic carbene-modulated reaction first designed asymmetrically functionalize diverse natural phenols with phthalides. Our method capable producing series new phthalidyl ethers under mild conditions good yields, enantioselectivity, functional group tolerance. Among these, compound ( R )- 3w exhibits excellent enantioselectivity-preferred curative activity against potato virus Y (PVY). Mechanistically, it proposed interacts nuclear inclusion body A (Nia) protein PVY at His150 residue. This binding impairs Nia’s function cleavage polyprotein, thereby inhibiting formation replication complex. The study provides insights into advancing protocol facilitate agrochemical discovery, our identified may serve potential lead future research PVY-Nia inhibitors.

Language: Английский

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Rational Design of Phytovirucide that Inhibits the Nucleocapsid Condensates of Tomato Spotted Wilt Virus

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: June 10, 2024

Chemical management of crop failures caused by plant viruses poses serious challenges in agricultural chemistry. Recently, phase separation has emerged as a key role the viral lifecycle, with discovery corresponding small molecule inhibitors medical field sparking significant interest. However, applicability this promising antiviral tactic for protection remains largely unknown. Herein, we have demonstrated that aggregation tomato spotted wilt virus (TSWV) nucleocapsid protein (N) is regulated RNA-induced separation, and disclosed new rationally designed inhibitor Z9. Z9 capable binding to TSWV N at R⁹⁴ Y¹⁸⁴ sites, preventing assembly RNA into aggregated ribonucleoproteins through separation. Mutations sites substantially diminish colocalization between processing bodies, interfering normal interaction RNA. This study provides opportunities separation-based anti-plant virus strategies.

Language: Английский

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Viral condensates formed by Pea enation mosaic virus 2 sequester ribosomal components and suppress translation

Virology, Journal Year: 2024, Volume and Issue: 601, P. 110301 - 110301

Published: Nov. 13, 2024

Language: Английский

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