Specific Influenza Therapy: Current State and Prospects (Review)

Abstract

Introduction. Respiratory infections are among the leaders in morbidity and mortality worldwide. The most severe cases of the disease are most often caused by the flu virus. Currently, there are many ways of specific prevention and treatment of influenza infection, but their effectiveness is far from ideal. This is due to the high variability of the influenza virus and the subsequent occurrence of resistance to the drugs used. In this regard, the improvement and development of antiviral drugs is an urgent task.Text. Influenza virus is an RNA-containing virus that causes massive epidemics and pandemics. Specific influenza prophylaxis includes vaccination. However, antigenic variability of the virus reduces the effectiveness of the vaccine, which requires constant costly development of its more advanced modifications. Specific treatment for influenza infection includes several classes of drugs, such as neuraminidase (NA) inhibitors oseltamivir, zanamivir and M2 protein inhibitors amantadine, rimantadine. At one time, these drugs were quite effective. But the formed resistance of influenza viruses to these drugs requires the creation of new or modifications of existing antiviral agents. Among the new domestic developments of antiviral drugs, histidyl-1-adamantainethylamine, which is a modification of the rimantadine molecule, has shown sufficient antiviral activity at the stage of preclinical studies. A representative of another class of drugs is arbidol (umifenovir), an inhibitor of hemagglutinin (HA) of the influenza virus. According to studies, the drug has high profiles of efficacy and safety, but the recommendation of the World Health Organization is to continue clinical trials. Currently, clinical studies of new classes of drugs are underway – baloxavir marboxil and favipiravir. Baloxavir marboxyl is a prodrug that is converted in vivo to baloxavir, an inhibitor of cap-dependent endonuclease. Favipiravir is an inhibitor of RNA-dependent RNA polymerase. In vitro studies in cell culture and in vivo in laboratory animals have shown higher efficacy of these drugs than the above with minimal toxicity.Conclusion. The rapid evolution of the influenza virus leads to a gradual decrease in the effectiveness of modern antiviral drugs. New compounds targeting targets important for virus reproduction are in clinical trials. The future of the fight against influenza depends on the outcome of these tests, according to which the compounds can become effective drugs for the prevention and treatment of influenza.

Keywords

• influenza virus
• antiviral activity
• neuraminidase inhibitors
• adamantane
• baloxavir
• rimantadine derivatives