Epidemiological Assessment, Integrative Phylogenetic Inference, and Structure-Guided in Silico Evaluation of Alkaloid Antivirals Targeting Zucchini Yellow Mosaic Virus (Zymv, Potyvirus Cucurbitaflavitesselati) and Watermelon Mosaic Virus (Wmv, Potyvirus Citrulli) Coat Proteins From Cucurbit Crops in Türkiye

Abstract

Zucchini yellow mosaic virus (ZYMV) and watermelon mosaic virus (WMV) are two economically significant potyviruses infecting cucurbit crops. This study aimed to investigate their presence in Van province (T & uuml;rkiye), characterize their coat protein (CP) genes, and evaluate theoretical antiviral activity of plant-derived alkaloids. A total of 440 cucurbit samples were screened using multiplex RT-PCR, revealing infection rates of 10% for ZYMV and 4.77% for WMV. CP genes of representative isolates were cloned, sequenced, and submitted to GenBank (ZYMV: OQ910198, OQ910199; WMV: OQ910200, OQ915352). Phylogenetic analysis indicated strong clustering with Turkish and Syrian isolates. Homology models of CP proteins were generated using Swiss-Model, Robetta, and Phyre2, with Swiss-Model yielding the most reliable 3D structures based on Ramachandran plot validation. Molecular docking of 15 alkaloids revealed that drupacine, sanguinarine, and antofine exhibited higher binding affinity to CP proteins than the commercial antiviral ribavirin, forming stable interactions at conserved residues. This is the first study from T & uuml;rkiye combining CP gene-based phylogeny and in silico structure-guided screening of natural antivirals for cucurbit viruses. The results suggest that CP is a promising antiviral target, and several alkaloids hold potential as eco-friendly inhibitors of potyviruses.