Emerging treatments

ZMapp

An experimental combination of three humanised monoclonal antibodies targeted at three Orthoebolavirus zairense glycoprotein epitopes, engineered for expression in tobacco plants.[174][175][176]​​ ZMapp was found to be protective when administered to non-human primates 24-48 hours after infection. Another study showed that the drug was able to rescue non-human primates when treatment is initiated up to 5 days after infection.[177] The PALM trial found that ZMapp was inferior to both atoltivimab/maftivimab/odesivimab and ansuvimab at reducing mortality.[163] The World Health Organization (WHO) suggests against treatment with ZMapp as the evidence is very uncertain regarding any true benefits or harms.[162]

Remdesivir

A prodrug of adenine nucleotide analogue that has potent activity against a variety of filoviruses in primate cell infection models. Initial studies have demonstrated excellent effectiveness as a treatment in non-human primates.[155] The PALM trial found that remdesivir was inferior to atoltivimab/maftivimab/odesivimab, ansuvimab, and ZMapp at reducing mortality.[163] The WHO suggests against treatment with remdesivir as the effects on mortality and serious adverse events remains very uncertain.[162] Remdesivir is now being used for the treatment of coronavirus disease 2019 (COVID-19).

Favipiravir

Favipiravir is an experimental antiviral drug that selectively inhibits viral RNA-dependent RNA polymerase. It is active against influenza viruses, West Nile virus, yellow fever virus, foot-and-mouth disease virus, as well as other flaviviruses, arenaviruses, bunyaviruses, and alphaviruses. The drug is currently approved in Japan for influenza pandemics, but has been found to be effective against orthoebolaviruses in mouse models.[178] Human phase II trials in Guinea used a higher dose than that used for influenza. The JIKI trial, a multi-centre non-randomised trial undertaken in Guinea in 2014-2015, suggested good tolerability at a higher dose in a low-resource setting, as well as a potential benefit in patients with low viral loads.[179]

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