Halovirs A-E, new antiviral agents from a marine-derived fungus of the genus Scytalidium.
Marine micro-organisms represent an under explored resource for the discovery of novel antiviral agents. Here, we describe a series of peptides designated halovirs A-E (1-5) that are produced during the saline fermentation of a marine-derived fungus of the genus Scytalidium. These lipophilic, linear peptides are potent in vitro inhibitors of the herpes simplex viruses 1 and 2. Evidence is presented that the halovirs directly inactivate herpes viruses, a mechanism of action that could be applicable in the prevention of HSV transmission. The total structures of these new compounds were established by a combination of spectral and chemical techniques. Salient structural features of the halovir hexapeptides include a nitrogen terminus acylated by myristic (C14) or lauric (C12) acid, an unusual Aib-Hyp dipeptide segment, and a carboxyl terminus reduced to a primary alcohol. A qualitative analysis of the secondary structures of these molecules using variable temperature NMR experiments and NOE analyses is also reported.
Rowley
David C
DC
Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California-San Diego, La Jolla, CA 92093-0204, USA. drowley@uri.edu
Kelly
Sara
S
Kauffman
Christopher A
CA
Jensen
Paul R
PR
Fenical
William
W
D000215:Acylation; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology; D001203:Ascomycota / Q000378:metabolism*; D002522:Chlorocebus aethiops; D005285:Fermentation; D018259:Herpesvirus 1, Human / Q000187:drug effects; D018258:Herpesvirus 2, Human / Q000187:drug effects; D006801:Humans; D008386:Marine Biology; D025282:Mycelium / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014709:Vero Cells / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D009842:Oligopeptides; C485457:halovir A; C485456:halovir B; C485454:halovir C; C485453:halovir D