Abstract
Favipiravir (FPV) is a novel antiviral drug acting as a competitive inhibitor of RNA-dependent RNA polymerase (RdRp), preventing viral transcription and replication. FPV was approved in Japan in 2014 for therapy of influenza unresponsive to standard antiviral therapies. FPV was also used in the therapy of Ebola virus disease (EVD) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this review, we discuss the mechanisms of action, pharmacokinetic parameters, toxicity, and adverse effects of FPV, as well as clinical studies evaluating the use of FPV in the therapy of influenza virus (IV) infection, EVD, and SARS-CoV-2 infection, along with its effectiveness in treating other human RNA infections.
Highlights
Favipiravir (FPV) is a purine nucleoside precursor. It acts as a competitive inhibitor of RNA-dependent RNA polymerase (RdRp)
Influenza Viruses Infections Since FPV was developed, many in vitro and in vivo in animal models studies confirmed that it inhibits all serotypes and strains of influenza A, B, and C viruses against which it was tested, including A(H1N1) pdm09, A(H5N1), and A(H7N9) avian virus [1,2,5,7,16,38,39,40,41,42,43,44,45,46,47,48,49,50]
The studies performed in animal models by Kiso et al, Itoh et al, and Watanabe et al demonstrated that FPV effectively protects mice from lethal infection with oseltamivir-sensitive or oseltamivir-resistant highly pathogenic H5N1 viruses, and it had an inhibitory activity, similar to or greater than that of oseltamivir and zanamivir, against the A(H1N1)pdm09 and A(H7N9) virus [41,42,43]
Summary
Favipiravir (FPV) (molecular formula: C5 H4 FN3 O2 ; molecular weight: 157.1 g/mol; synonyms: 6-fluoro-3-hydroxy-2-pyrazinecarboxamide; T-705; 259793-96-9; and 6-fluoro3-oxo-3,4-dihydropyrazine-2-carboxamide) is a purine nucleoside precursor. It acts as a competitive inhibitor of RNA-dependent RNA polymerase (RdRp). Through the screening of a chemical library of Toyama Chemical Co., Ltd., using a plaque reduction assay for antiviral activity against the influenza virus (IV), A/PR/8/34, a lead compound, which was designated as T-1105 afterward, was found to be effective. In 2014, T-705 (FPV) was approved as a drug in Japan for novel epidemic influenza strains that were unresponsive to standard antiviral therapies [3].
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