Virustomycin A

Virustomycin A (AM-2604 A) is an 18-membered macrolide antibiotic isolated from Streptomyces species. It exhibits potent in vitro inhibitory activity against various RNA and DNA viruses and shows selective antitrypanosomal activity. Mechanistic studies in Trichomonas foetus demonstrated that virustomycin A inhibits RNA, DNA and protein biosynthesis, with the most pronounced effect on RNA synthesis. The compound interferes with nucleotide formation from uridine and adenosine without blocking nucleoside transport or directly inhibiting uridine kinase or uracil phosphoribosyltransferase, suggesting disruption of cellular phosphate donor formation, possibly the ATP-generating system. Biosynthetic investigations identified a type I polyketide synthase gene cluster responsible for virustomycin A assembly. These findings define virustomycin A as a bioactive macrolide that suppresses nucleic acid biosynthesis through interference with nucleotide metabolism.