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

Megan J. Brooks, Elena I. Burtseva, Philip J. Ellery, Glenn A. Marsh, Andrew M. Lew, Anatoly N. Slepushkin, Suzanne M. Crowe, Gregory A. Tannock

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.