Favipiravir (T-705) protects against Nipah virus infection in the hamster model

Abstract

Nipah and Hendra viruses are recently emerged bat-borne paramyxoviruses (genus Henipavirus) causing severe encephalitis and respiratory disease in humans with fatality rates ranging from 40–75%. Despite the severe pathogenicity of these viruses and their pandemic potential, no therapeutics or vaccines are currently approved for use in humans. Favipiravir (T-705) is a purine analogue antiviral approved for use in Japan against emerging influenza strains; and several phase 2 and 3 clinical trials are ongoing in the United States and Europe. Favipiravir has demonstrated efficacy against a broad spectrum of RNA viruses, including members of the Paramyxoviridae, Filoviridae, Arenaviridae families, and the Bunyavirales order. We now demonstrate that favipiravir has potent antiviral activity against henipaviruses. In vitro, favipiravir inhibited Nipah and Hendra virus replication and transcription at micromolar concentrations. In the Syrian hamster model, either twice daily oral or once daily subcutaneous administration of favipiravir for 14 days fully protected animals challenged with a lethal dose of Nipah virus. This first successful treatment of henipavirus infection in vivo with a small molecule drug suggests that favipiravir should be further evaluated as an antiviral treatment option for henipavirus infections.

Nano-based approach to combat emerging viral (NIPAH virus) infection

“…54 A recent hit on broad-spectrum small molecule antiviral purine analogue previously mentioned Favipiravir (T-705) which inhibits NIV and HeV replication in vitro with a minimal cytotoxic effect of highest concentration tested, having a CC 50 value of N1000 μl (as observed in Hamster model) has provided a way to fight against the cytopathic effect of deadly NiV, HeV like paramyxoviruses. 6 35 It is not late when one day due to the consistent change in their genome these pathogens would get resistance to the conventional drugs which are unidirectional and have no specific targeted. These limitations could be ameliorated by finding a novel therapy with multiple pathways and biomarkers for the target oriented action.…”

“…5 Moreover, the conventional unidirectional serological diagnosis and therapeutics orchestrate numeral shortcomings such as cost deficit, sophisticated preparation procedures, efficient only on postexposure prophylaxis and reduced amount of the product in consistent with human population and livestock to be vaccinated. 5,6 Majority of the therapeutics developed basically includes monoclonal antibodies targeting viral surface proteins such as F, G or M proteins. [7][8][9] Further a number of broad spectrum antiviral agents such as nucleoside analogues namely rebavirin, GS-441524, GS-5734 (remdesivir), R1479 (balapiravir) and most recent drug favipiravir (T-705; 6-flouro-3-hydroxy-2-pyrazinecarboxamine) which is an inhibitor of viral RNA-dependent RNA polymerase have shown certain degree of efficiency against this virus.…”

“…[7][8][9] Further a number of broad spectrum antiviral agents such as nucleoside analogues namely rebavirin, GS-441524, GS-5734 (remdesivir), R1479 (balapiravir) and most recent drug favipiravir (T-705; 6-flouro-3-hydroxy-2-pyrazinecarboxamine) which is an inhibitor of viral RNA-dependent RNA polymerase have shown certain degree of efficiency against this virus. 6 But lack of target specific action and probability of host cell toxicity are the major limitations of these synthetic drugs. 10,11 Taking into consideration, the severity of the infection and imperative necessity for a novel multidirectional, target specific and, non-toxic nature; the tunable nanotechnology based approaches seems to be a promising alternative.…”

Emerging trends of Nipah virus: A review

“…In Singapore outbreak, acyclovir was given to all NiV encephalitis patients and only one death reported due NiV infection, but the role of acyclovir drug is still unclear . In a recent in vivo study, Favipiravir (T‐705) antiviral showed promising results when tested on NiV infected golden hamsters . A study involving use of vaccine against NiV has shown promising results in hamster models .…”

“…A study involving use of vaccine against NiV has shown promising results in hamster models . As Nipah outbreaks are often associated with high mortality and have great impact on community health, there is a strong need of specific antiviral agents for early treatment of NiV …”