Strategies for the development of influenza drugs: Basis for new efficient combination therapies

Abstract

Only four drugs are approved for the specific treatment of acute influenza infections worldwide. These drugs address either the viral neuraminidase or the M2-channel but suffer from poor efficacy and the rapid emergence of drug resistances. Some additional drugs are launched in few countries, but their efficacy is relatively low and often limited to certain influenza strains. Ideally, new drugs should possess a broad potency against all influenza viruses and be less susceptible to the development of resistances. The propagation cycle of the influenza virus offers many possibilities for the development of new anti-influenza drugs. Various compounds addressing viral targets reached clinical development, from which the most-advanced candidate is the polymerase inhibitor favipiravir. A promising strategy could be also the inhibition of host targets and signaling pathways, e.g., by already approved kinase inhibitors, anti-inflammatory drugs, or immunomodulatory agents. However, the benefit of these agents has to be demonstrated in controlled clinical trials. A broader arsenal of approved drugs will offer the possibility for more efficient combinatorial therapies in the future. The first proof of concept studies for such multiple drug therapies in infected mice revealed beneficial effects. Moreover, this strategy should reduce the rapid emergence of resistant influenza strains.