South American haemorrhagic fevers - Emerging treatments

Favipiravir

Favipiravir (previously known as T-705) selectively inhibits viral RNA-dependent RNA polymerase. Originally developed for the treatment of influenza, it has been shown to be active against a wide variety of RNA viruses including flaviviruses, bunyaviruses, alphaviruses, and arenaviruses in vitro and in animal models.[38] Favipiravir has been shown to be effective against the New World arenavirus, Pichinde virus, in guinea pig models.[4] It has also been studied in Junin virus-infected guinea pig models and has shown promise when administered in intraperitoneal format, with substantial improvement in survival (78%) compared with ribavirin (33% to 40%).[39] Favipiravir has not yet been through human trials for arenaviruses, but has been shown to be safe when administered to patients with Ebola virus disease, with the potential for improved survival at low viral loads.[40] A study on cynomolgus macaques with Lassa fever viraemia demonstrated good antiviral efficacy; however, it is unclear how this will translate to humans.[41] There is one case report of a patient with Argentine haemorrhagic fever treated with a combination of favipiravir and ribavirin.[42]

Gabapentin

There are data suggesting that Junin viral entry to cells may be mediated by voltage-gated calcium channel subunits.[43] Blockage of these channels has been shown to result in reduced Junin virus-cell fusion and entry into cells. Gabapentin, which is normally used for neuropathic pain, blocks the alpha(2)delta subunit of voltage-gated calcium channels. Trials in a mouse model have found that gabapentin can inhibit Junin virus infection. There have been no clinical trials as yet.

Monoclonal antibodies

Projects to develop monoclonal antibody products for the SAHFs are underway. Therapeutic candidates have been identified for Machupo virus and Junin virus, the viruses responsible for Bolivian and Argentine haemorrhagic fevers respectively.[4][44][45] In one study, monoclonal antibodies provided 100% protection when initiated 6 days after infection and 92% protection when initiated 7 days after infection in a guinea pig model of Argentine haemorrhagic fever.[46] A study in 2021 of an anti-Junin monoclonal antibody in cynomolgus macaques demonstrated a 100% survival rate at 6 days post-inoculation, and 50% survival rate at 8 days post-inoculation.[47] Combined with past use of immune plasma for Argentine haemorrhagic fever, this is an area that may prove promising if a product can be developed for the relevant diseases.[48]