Innovative Arylimidazole‐Fused Phytovirucides via Carbene‐Catalyzed [3+4] Cycloaddition: Locking Viral Cell‐To‐Cell Movement by Out‐Competing Virus Capsid‐Host Interactions

Autor: Chunle Wei, Chunni Zhao, Jiao Li, Chunyi Li, Baoan Song, Runjiang Song
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Advanced Science, Vol 11, Iss 19, Pp n/a-n/a (2024)
Druh dokumentu: article
ISSN: 2198-3844
DOI: 10.1002/advs.202309343
Popis: Abstract The control of potato virus Y (PVY) induced crop failure is a challengeable issue in agricultural chemistry. Although many anti‐PVY agents are designed to focus on the functionally important coat protein (CP) of virus, how these drugs act on CP to inactivate viral pathogenicity, remains largely unknown. Herein, a PVY CP inhibitor ‐3j (S) is disclosed, which is accessed by developing unusually efficient (up to 99% yield) and chemo‐selective (> 99:1 er in most cases) carbene‐catalyzed [3+4] cycloaddition reactions. Compound ‐3j bears a unique arylimidazole‐fused diazepine skeleton and shows chirality‐preferred performance against PVY. In addition, ‐3j (S) as a mediator allows ARG191 (R191) of CP to be identified as a key amino acid site responsible for intercellular movement of virions. R191 is further demonstrated to be critical for the interaction between PVY CP and the plant functional protein NtCPIP, enabling virions to cross plasmodesmata. This key step can be significantly inhibited through bonding with the ‐3j (S) to further impair pathogenic behaviors involving systemic infection and particle assembly. The study reveals the in‐depth mechanism of action of antiviral agents targeting PVY CP, and contributes to new drug structures and synthetic strategies for PVY management.
Databáze: Directory of Open Access Journals
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