Antiviral activity of arbidol, a broad‐spectrum drug for use against respiratory viruses, varies according to test conditions

Abstract

The therapeutic activity of arbidol was investigated against representatives of seven different virus families. Its 50% median effective concentration (EC(50) ) was 0.22-11.8 µg/ml (0.41-22 nM). Therapeutic indices of 91 were obtained for type 1 poliovirus and 1.9-8.5 for influenza A and B, human paramyxo-3, avian infectious bronchitis-, and Marek's disease viruses. Arbidol was more inhibitory for influenza A/Aichi/2/68 (H3N2) virus than rimantadine or amantadine (EC(50) 10 vs. >15 and >31.6 µg/ml); greater inhibition occurred when end-points were expressed as TCID(50) s. For respiratory syncytial virus (RSV), a reduction in plaque size but not number was observed. However, when the drug was added to infected cultures (≥5 µg/ml), a 3-log reduction in titer occurred. Arbidol did not inhibit directly influenza A/Aichi/2/68 hemagglutinin (HA) or neuraminidase (NA) activity, but inhibition of fusion between the viral envelope and chicken red blood cells occurred when added at 0.1 µg/ml prior to infection. Arbidol induced changes to viral mRNA synthesis of the PB2, PA, NP, NA, and NS genes in MDCK cultures infected with influenza A/PR/8/34. There was no indirect evidence of enhancement of interferon-α by arbidol following infection with A/Aichi/2/68. Arbidol neither reduced lung viral titers nor caused a significant reduction of lung consolidation in BALB/c mice after administration by the oral and intraperitoneal (i.p.) routes and intranasal challenge with influenza A/Aichi/2/68. A small reduction in lung consolidation, but not viral titer, occurred after i.p. administration and subsequent challenge with RSV. The results indicate the potential of arbidol as a broad-spectrum respiratory antiviral drug.

Structural basis of influenza virus fusion inhibition by the antiviral drug Arbidol

“…Previous in vitro and in vivo studies have shown that Arbidol has broad-spectrum activity against influenza viruses (16)(17)(18)21). Comparison of the Arbidol-binding site in group 2 HAs against the corresponding region in group 1 HA [H1N1 A/Puerto Rico/8/1934 (H1/PR8; PDB ID code 1RU7)] reveals important structural differences between the two groups ( Fig.…”

“…Arbidol (umifenovir) is a broad-spectrum antiviral against a number of enveloped and nonenveloped viruses such as influenza, respiratory syncytial (RSV), adenovirus, Coxsackie B5, parainfluenza, Ebola (EBOV), and hepatitis B and C (14)(15)(16)(17)(18)(19)(20). Arbidol demonstrates broad activity against diverse strains and subtypes of influenza A and B viruses and is effective in mice infected with A/California/07/2009 (H1N1), A/Puerto Rico/8/1934 Significance Influenza virus is an important human pathogen.…”

“…(H1N1), and A/Aichi/2/1969 (H3N2) influenza A viruses (14)(15)(16)(17)(18)21). Arbidol is used primarily as an over-the-counter drug in Russia and China for prophylaxis and treatment of acute respiratory infections including influenza, but has not yet gained acceptance in other countries.…”

Clinical efficacy of Аrbidol (umifenovir) in the therapy of influenza in adults: Preliminary results of the multicenter double-blind randomized placebo-controlled study ARBITR

“…Противовирусная активность умифеновира in vitro и in vivo выявлена в отношении различных вирусов, в част-ности вирусов гриппа А и В, включая сезонные и высоко-патогенные подтипы A(H1N1)pdm09 и A(H5N1), ряда других возбудителей ОРВИ (аденовирус, респираторно-синцитиальный вирус, коронавирус, или вирус атипич-ной пневмонии -ТОРС, риновирус, вирус парагриппа) [22][23][24][25].…”

Crystal Structures, Thermal Analysis, and Dissolution Behavior of New Solid Forms of the Antiviral Drug Arbidol with Dicarboxylic Acids

“…Arbidol (or umifenovir) (1-methyl-2-phenylthiomethyl-3-carbethoxy-4-dimetylaminomethyl-5-hydroxy-6-bromoindole) is a Russian-made indole-derivative molecule with antiviral activity [10,11] and immunomodulatory effect ( Figure 1) [12,13]. Arbidol activity results from its ability to inhibit fusion of a virus lipid envelope with endosome membranes located within the cell.…”