Efficacy of Favipiravir (T-705) in Rabies Postexposure Prophylaxis

Abstract

Rabies is a fatal encephalitis caused by rabies virus (RABV), and no antiviral drugs for RABV are currently available. We report for the first time the efficacy of favipiravir (T-705) against RABV in vitro and in vivo. T-705 produced a significant, 3–4 log10 reduction in the multiplication of street and fixed RABV strains in mouse neuroblastoma Neuro-2a cells, with half-maximal inhibitory concentrations of 32.4 µM and 44.3 µM, respectively. T-705 significantly improved morbidity and mortality among RABV-infected mice when orally administered at a dose of 300 mg/kg/day for 7 days, beginning 1 hour after inoculation. T-705 significantly reduced the rate of virus positivity in the brain. Furthermore, the effectiveness of T-705 was comparable to that of equine rabies virus immunoglobulin for postexposure prophylaxis. Collectively, our results suggest that T-705 is active against RABV and may serve as a potential alternative to rabies immunoglobulin in rabies postexposure prophylaxis.

Favipiravir, an anti-influenza drug against life-threatening RNA virus infections

“…Then, chain elongation stops at the site of favipiravir incorporation, and elongation does not proceed because favipiravir functions as a chain terminator. This RNA-favipiravir(-RdRp) J o u r n a l P r e -p r o o f (Bai, et al, 2016;Bixler, et al, 2018;Jacobs, et al, 2015;Oestereich, Ludtke, et al, 2014;Sissoko, et al, 2016;Smither, et al, 2014) Severe fever with thrombocytopenia syndrome (SFTS) caused by a virus infection 12-30% b (Gowen, Westover, Miao, et al, 2017a;Tani, et al, 2016;Yasukawa, 2016) Severe influenza (Cao, 2018;Wang et al, 2019) Lassa virus infection 1% a , severe cases 15% a (Gowen, Westover, Sefing, et al, 2017b;Mendenhall, et al, 2011;Oestereich, et al, 2016;Raabe, et al, 2017;Safronetz, et al, 2015) Rabies Approximately 100% a, b (Baker, 2017;Yamada, Noguchi, Komeno, Furuta, & Nishizono, 2015) Norovirus infection 50,000 deaths/year b (Arias, Thorne, & Goodfellow, 2014;Ruis, et al, 2018) Avian influenza A(H5N1) 52.8% (Sep 9, 2019) a Favipiravir is effective against influenza in animals and humans and has…”

New Nucleoside Analogues for the Treatment of Hemorrhagic Fever Virus Infections

“…Ta king into account that rhabdo-and filoviruses are closely related,i ti sn ot surprising that favipiravir has also been advocated for the postexposure prophylaxis of rabiesvirus, as ap otential alternative to rabies immunoglobulin. [78] The compounds described here can be considered as either adenine derivatives (3-deazaneplanocin A, galidesivir,r emdesivir or guanine derivatives (ribavirin), EICAR, pyrazofurin,f avipiravir). This is immediatelyo bvious for the adenine derivatives, which can be expected to interferew ith viral RNA synthesis at the level of the RdRp (RNA-dependentR NA polymerase), where they can serve as competitive inhibitors with respectt o ATP( based on the hydrogen bonds formed between adenine and uracil) ( Figure 2).…”

Molecular Mechanism of Action of Repurposed Drugs and Traditional Chinese Medicine Used for the Treatment of Patients Infected With COVID-19: A Systematic Scoping Review

“…Favipiravir (FPV; T-705) was developed by Toyama Chemicals in 2002 and has been approved in Japan for the treatment of influenza virus infections ( Figure 6) [65,66]. Favipiravir has demonstrated antiviral activity against a wide range of RNA viruses including norovirus [67], Zika virus [68], foot-andmouth disease virus (FMDV) [69], Rabies [70] and Ebola virus [71,72]. Like remdesivir, favipiravir inhibits viral RNA synthesis through chain termination [74,75].…”