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Arbidol (Umifenovir): A Broad-Spectrum Antiviral Drug That Inhibits Medically Important Arthropod-Borne Flaviviruses.

ABSTRACT: Arthropod-borne flaviviruses are human pathogens of global medical importance, against which no effective small molecule-based antiviral therapy has currently been reported. Arbidol (umifenovir) is a broad-spectrum antiviral compound approved in Russia and China for prophylaxis and treatment of influenza. This compound shows activities against numerous DNA and RNA viruses. The mode of action is based predominantly on impairment of critical steps in virus-cell interactions. Here we demonstrate that arbidol possesses micromolar-level anti-viral effects (EC₅₀ values ranging from 10.57 ± 0.74 to 19.16 ± 0.29 µM) in Vero cells infected with Zika virus, West Nile virus, and tick-borne encephalitis virus, three medically important representatives of the arthropod-borne flaviviruses. Interestingly, no antiviral effects of arbidol are observed in virus infected porcine stable kidney cells (PS), human neuroblastoma cells (UKF-NB-4), and human hepatoma cells (Huh-7 cells) indicating that the antiviral effect of arbidol is strongly cell-type dependent. Arbidol shows increasing cytotoxicity when tested in various cell lines, in the order: Huh-7 < HBCA < PS < UKF-NB-4 < Vero with CC₅₀ values ranging from 18.69 ± 0.1 to 89.72 ± 0.19 µM. Antiviral activities and acceptable cytotoxicity profiles suggest that arbidol could be a promising candidate for further investigation as a potential therapeutic agent in selective treatment of flaviviral infections.

SUBMITTER: Haviernik J

PROVIDER: S-EPMC5923478 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Arbidol (Umifenovir): A Broad-Spectrum Antiviral Drug That Inhibits Medically Important Arthropod-Borne Flaviviruses.

Haviernik Jan J Štefánik Michal M Fojtíková Martina M Kali Sabrina S Tordo Noël N Rudolf Ivo I Hubálek Zdeněk Z Eyer Luděk L Ruzek Daniel D

Viruses 20180410 4

Arthropod-borne flaviviruses are human pathogens of global medical importance, against which no effective small molecule-based antiviral therapy has currently been reported. Arbidol (umifenovir) is a broad-spectrum antiviral compound approved in Russia and China for prophylaxis and treatment of influenza. This compound shows activities against numerous DNA and RNA viruses. The mode of action is based predominantly on impairment of critical steps in virus-cell interactions. Here we demonstrate th ...[more]

PMID: 29642580

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Project description:An indole derivative umifenovir (Arbidol) is one of the most widely used antiviral drugs for the prevention and treatment of COVID-19 and some other viral infections. The purpose of the present study was to shed light on the transformation processes of umifenovir in municipal wastewater, including disinfection with active chlorine, as well as to assess the levels of the antiviral drug and its metabolites entering and accumulating in natural reservoirs under conditions of the SARS-CoV-2 pandemic. The combination of high-performance liquid chromatography with electrospray ionization high-resolution mass-spectrometry and inductively coupled plasma mass spectrometry was used for tentative identification and quantification of umifenovir and its transformation products in model reaction mixtures and real samples of wastewater, river water, biological sludge and bottom sediments taken at the wastewater treatment plant in Arkhangelsk, a large cultural and industrial center at the Russian North. Laboratory experiments allowed identifying fifteen bromine-containing transformation products, forming at the initial stages of the chlorination and fourteen classic volatile and semi volatile disinfection by-products with bromoform as the dominant one. Chlorinated derivatives are only the minor disinfection by-products forming by substitution of alkylamine group in the aromatic ring. The schemes of umifenovir transformation in reactions with dissolved oxygen and sodium hypochlorite are proposed. Two established primary transformation products formed by oxidation of the thioether group to sulfoxide and elimination of thiophenol were detected in noticeable concentrations in the wastewater together with their precursor. The level of umifenovir reached 1.3 mg kg-1 in the sludge and municipal wastewater treat contained 1 μg L-1 of that drug, while its removal during biological wastewater treatment was about 40%. Pronounced accumulation of umifenovir and its transformation products in biological sludge and bottom sediments of natural reservoirs may be a source of the future secondary pollution of the environment.

Dataset Information

Arbidol (Umifenovir): A Broad-Spectrum Antiviral Drug That Inhibits Medically Important Arthropod-Borne Flaviviruses.

Publications

Arbidol (Umifenovir): A Broad-Spectrum Antiviral Drug That Inhibits Medically Important Arthropod-Borne Flaviviruses.

Similar Datasets

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