Lactimidomycin is a broad-spectrum inhibitor of dengue and other RNA viruses

• Lactimidomycin inhibits dengue virus translation and reduces viral replication without cytotoxicity.
• Lactimidomycin also inhibits other members of the Flaviviridae, Picornaviridae, and Rhabdoviridae families.
• Inhibition of poliovirus and vesicular stomatitis virus is associated with protection from virus-induced cytopathic effects.

Dengue virus, a member of the Flaviviridae family, is a mosquito-borne pathogen and the causative agent of dengue fever. Despite the nearly 400 million new infections estimated annually, no vaccines or specific antiviral therapeutics are currently available. We identified lactimidomycin (LTM), a recently established inhibitor of translation elongation, as a potent inhibitor of dengue virus 2 infection in cell culture. The antiviral activity is observed at concentrations that do not affect cell viability. We show that Kunjin virus and Modoc virus, two other members of the Flavivirus genus, as well as vesicular stomatitis virus and poliovirus 1, are also sensitive to LTM. Our findings suggest that inhibition of translation elongation, an obligate step in the viral replication cycle, may provide a general antiviral strategy against fast-replicating RNA viruses.