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Favipiravir

Manufactured by Fujifilm
Sourced in Japan

Favipiravir is a broad-spectrum antiviral medication developed by Fujifilm. It is an RNA-dependent RNA polymerase (RdRp) inhibitor, which prevents the replication of viral RNA. Favipiravir is used as a treatment for various viral infections, but its specific applications and efficacy may vary. For detailed information on the intended use and performance of this product, please consult the relevant medical authorities or product documentation.

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4 protocols using favipiravir

1

Antiviral Efficacy of Favipiravir and Ribavirin against HRTV

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Each group of three IFNAR−/− mice was anesthetized with midazolam, medetomidine, and a butorphanol tartrate combination, was intraperitoneally inoculated with 1 × 107 TCID50 of HRTV at a volume of 200 μL per mouse, and was treated with antiviral agents, as described below. For the mock infection, the same volume of DMEM-2FBS was used. The favipiravir-treated and ribavirin-treated mice were orally administered 60 mg/kg of favipiravir (FUJIFILM Toyama Chemical Co., Ltd., Tokyo, Japan) and 100 mg/kg of ribavirin (FUJIFILM Wako Chemicals), respectively, dissolved in a 0.5% methyl cellulose (Sigma-Aldrich, St. Louis, MO, USA) solution, at a volume of 200 μL per mouse, once a day for 5 days. The placebo-treatment mice were administered the same volume of 0.5% methylcellulose once a day for 5 days. The first administration of each compound was initiated immediately after the HRTV inoculation. Each mouse was monitored daily for the development of clinical signs, including bodyweight, and blood samples were obtained by tail-vein puncture at 2 and 4 days postinfection to measure the viral RNA levels.
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2

Virus Infection Assay in Cell Lines

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Human embryonic kidney (293T) and African green monkey kidney (Vero 76) cell lines were maintained in Dulbecco’s modified Eagle’s medium (DMEM; Invitrogen, CA, USA) with 10% fetal bovine serum (FBS) and 1% penicillin and streptomycin. The Candid #1 vaccine strain of JUNV was kindly provided by Dr. Juan C. de la Torre (Scripps Research Institute, California, USA) [63 (link)]. Favipiravir was obtained from FUJIFILM Toyama Chemical CO., LTD. (Toyama, Japan). Ribavirin (Sigma Aldrich, MO, USA) and remdesivir (Cayman, MI, USA) were purchased. All compounds were dissolved in 100% dimethyl sulfoxide (DMSO) and stored at −30°C until use.
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3

Cell Cultures and Compound Screening

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Human embryonic kidney HEK293T, human hepatocellular carcinoma Huh7, African green monkey kidney Vero, and hamster kidney BHK cells were cultured in Dulbecco’s modified Eagle medium (DMEM; Nacalai tesque, Kyoto, Japan) supplemented with 10% fetal bovine serum (FBS; Invitrogen, Waltham, MA, USA), 100 μg/mL of streptomycin, and 100 units of penicillin (Nacalai tesque). Favipiravir (6-fluoro-3-hydroxy-2-pyrazinecarboxamide) and ribavirin (1-b-D-ribofuranosyl-1,2,4-triazole-3-carboxamide) were obtained from Fujifilm Toyama Chemical Co. Ltd. (Toyama, Japan) and Fujifilm Wako Pure Chemical (Osaka, Japan), respectively. The compound libraries, namely FDA-approved Drug Library and G protein-coupled receptor (GPCR) Compound Library, were purchased from TargetMol (Boston, MA, USA). MMF, MTX, clofarabine, and bleomycin sulfate were purchased from Tokyo Chemical Industry (Tokyo, Japan). Thonzonium bromide, everolimus, and niclosamide were purchased from MedChemExpress (Monmouth Junction, NJ, USA).
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4

Randomized COVID-19 Treatment Trial

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A prescreening visit (usually by telephone) briefly assessed eligibility and collected the following information: study site, age (≤55 versus >55 years), sex, height and weight (to calculate body mass index (BMI)), symptomatic or asymptomatic, current smoking status (current smoker, non-smoker, ex-smoker), ethnicity, previous COVID-19 specific vaccination (yes/no), and presence/absence of the following comorbidities: diabetes, hypertension, ischaemic or other heart disease, and chronic respiratory disease. These variables were used as part of the minimisation strategy to randomise participants into the 4 arms 1:1:1:1 using a centralised concealed online process to assign participants to a medication kit number.
Trial medication kits, prepared by RenaClinical, were coded to maintain double blinding (investigators and participants). Kits contained favipiravir or colour and size matched placebo 200-mg tablets supplied by Fujifilm Toyama Chemical Co. and lopinavir-ritonavir 200-mg/50-mg tablets (AbbVie) or colour and size matched placebos (RenaClinical).
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