Antiviral activity of arbidol, a broad-spectrum drug for use against respiratory viruses, varies according to test conditions.
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.
Department of Biotechnology and Environmental Biology, RMIT University, Bundoora, Victoria, Australia.
Megan J
MJ
Brooks
Elena I
EI
Burtseva
Philip J
PJ
Ellery
Glenn A
GA
Marsh
Andrew M
AM
Lew
Anatoly N
AN
Slepushkin
Suzanne M
SM
Crowe
Gregory A
GA
Tannock
D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002460:Cell Line; D004195:Disease Models, Animal; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology*; D008168:Lung / Q000473:pathology / Q000821:virology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests / Q000379:methods; D009976:Orthomyxoviridae Infections / Q000188:drug therapy; D012141:Respiratory Tract Infections / Q000821:virology*; D019562:Viral Load; D010948:Viral Plaque Assay; D014780:Viruses / Q000187:drug effects* / Q000302:isolation & purification; D013440:Sulfides
D000998:Antiviral Agents; D007211:Indoles; C086979:umifenovir; D013440:Sulfides