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.

Antiviral chemotherapeutic agents against respiratory viruses: where are we now and what's in the pipeline?

PURPOSE OF REVIEW: The emergence of severe acute respiratory syndrome in late 2002 and the recent outbreaks of avian influenza in Asia are timely reminders of the ever present risks from respiratory viral diseases. Apart from influenza, there are no vaccines and very few antiviral chemotherapeutic agents available for the prevention and treatment of respiratory viral infections-the most common cause of human illness. If the current H5N1 avian influenza outbreak ever assumes the role of a pandemic, formidable technical difficulties relating to the properties of the agent, itself, will ensure that vaccines will only become available after a significant lead time and then only to a relatively small percentage of the population. The use of existing antivirals could be critical in limiting the initial spread of a pandemic, although their use in the control of epidemics caused by nonpandemic viruses has not been evaluated. It is against this background that a review of recent developments in respiratory antivirals has been undertaken. RECENT FINDINGS: The late 1990s were a period of unprecedented activity in the development of new and much superior antivirals for the treatment of influenza infections. However, during the past 2 to 3 years and largely for commercial reasons, there has been a decline in interest in their further development by major drug companies. This situation may soon change with the possible advent of new pandemic viruses, and moves are afoot in several countries to consider the stockpiling of antivirals. The neuraminidase inhibitors zanamivir and oseltamivir, and the M2 inhibitors amantadine and rimantadine, remain the only options for controlling respiratory disease caused by influenza viruses, although the latter two could not be used against very recent H5N1 strains. There are several other neuraminidase inhibitors in development. Compounds with activity against other respiratory viruses, notably rhinoviruses, are also in development, many based on a newer knowledge of viral protein structure and function (rational drug design). SUMMARY: The following is an overview of recent papers on the further development of neuraminidase inhibitors against influenza viruses and on recent development of newer antivirals against RSV and rhinoviruses. Where possible, comparisons are made with existing antivirals. For considerations of space, this review has been structured around stages in the replication cycle of significant respiratory viruses that have been traditionally used as targets for inhibition.