Open AccessDevelopment of Peptide-Conjugated Morpholino Oligomers as Pan-Arenavirus Inhibitors
Author(s) -
Benjamin W. Neuman,
Lydia H. Bederka,
David A. Stein,
Joey Ting,
Hong M. Moulton,
Michael J. Buchmeier
Publication year - 2011
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.00650-11
Subject(s) - arenavirus , lymphocytic choriomeningitis , virology , biology , virus , morpholino , viral replication , rna , genetics , gene , in vitro , cytotoxic t cell , zebrafish
Members of theArenaviridae 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 andin 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.