Development of peptide-conjugated morpholino oligomers as pan-arenavirus inhibitors.

TitleDevelopment of peptide-conjugated morpholino oligomers as pan-arenavirus inhibitors.
Publication TypeJournal Article
Year of Publication2011
AuthorsNeuman BW, Bederka LH, Stein DA, Ting JPC, Moulton HM, Buchmeier MJ
JournalAntimicrobial agents and chemotherapy
Volume55
Issue10
Pagination4631-8
Date Published2011 Oct
ISSN1098-6596
KeywordsAnimals, Antiviral Agents, Arenaviridae Infections, Arenavirus, Arenaviruses, New World, Cell Line, Cercopithecus aethiops, Genome, Viral, Junin virus, Lymphocytic choriomeningitis virus, Mice, Microbial Sensitivity Tests, Morpholinos, Peptides, Pichinde virus, Protein Biosynthesis, RNA, Viral, Vero Cells, Virus Replication
Abstract

Members of the Arenaviridae family are a threat to public health and can cause meningitis and hemorrhagic fever, and yet treatment options remain limited by a lack of effective antivirals. In this study, we found that peptide-conjugated phosphorodiamidate morpholino oligomers (PPMO) complementary to viral genomic RNA were effective in reducing arenavirus replication in cell cultures and in vivo. PPMO complementary to the Junín virus genome were designed to interfere with viral RNA synthesis or translation or both. However, only PPMO designed to potentially interfere with translation were effective in reducing virus replication. PPMO complementary to sequences that are highly conserved across the arenaviruses and located at the 5' termini of both genomic segments were effective against Junín virus, Tacaribe virus, Pichinde virus, and lymphocytic choriomeningitis virus (LCMV)-infected cell cultures and suppressed viral titers in the livers of LCMV-infected mice. These results suggest that arenavirus 5' genomic termini represent promising targets for pan-arenavirus antiviral therapeutic development.

Alternate JournalAntimicrob. Agents Chemother.