LHF-535 is a Broad-spectrum Inhibitor of Arenavirus Entry

Arenaviruses are a significant cause of hemorrhagic fever, an often-fatal disease. Arenaviruses are single-stranded ribonucleic acid (RNA) viruses that cause chronic infections in rodents and zoonotically acquired disease in humans through rodent excreta, especially urine. Especially, arenaviruses are classic causes of viral hemorrhagic fever syndrome.

Recently, researchers are developing LHF-535, a small-molecule viral entry inhibitor that targets the arenavirus envelope glycoprotein. Gratifyingly, LHF-535 is a small molecule antiviral with potent activity against Lassa and other arenaviruses. Moreover, LHF-535 is a therapeutic candidate for Lassa fever and other hemorrhagic fevers of arenavirus origin. LHF-535 inhibits virus entry into target host cells and serves to suppress viral replication. Taken together, LHF-535 is an optimized lead compound with good oral bioavailability and pharmacokinetics, supporting once-daily administration. Besides, LHF-535 has demonstrated safety and efficacy in preclinical models, including reduced virus titers and enhanced survival in animal models of arenavirus pathogenesis.

In this study, Ikenna G. Madu, et al evaluated LHF-535, which targets the arenavirus envelope glycoprotein, for broad-spectrum activity against Lassa viruses of different lineages and related arenaviruses that cause hemorrhagic fever diseases. Fortunately, LHF-535 targets a viral virulence determinant, the mutation of which may result in the emergence of drug-resistant viruses, but with reduced capacity for virulence. LHF-535, a small-molecule antiviral under development for the treatment and prevention of Lassa fever and other hemorrhagic fevers such as Argentine (Junín virus) and Bolivian (Machupo virus) hemorrhagic fevers. All in all, LHF-535 exhibits potent antiviral activity against a broad array of hemorrhagic fever arenaviruses.

Madu IG, et al. A potent Lassa virus antiviral targets an arenavirus virulence determinant. PLoS Pathog. 2018 Dec 21;14(12):e1007439.