What question did this study set out to answer?

The aim is to evaluate the current landscape of direct-acting antivirals for influenza and identify challenges.

June 11, 2026Microbiology and Molecular Biology Reviews0 citations

Effective influenza treatment: a comprehensive review of challenges and advances

KPKristina PomeshikovaFederal Center Research Fundamentals of Biotechnology APArtem PoromovPeoples' Friendship University of Russia MSMichaela SchmidtkeJena University Hospital

Key Points

The aim is to evaluate the current landscape of direct-acting antivirals for influenza and identify challenges.
Reviewed existing antiviral drugs including DAAs, neuraminidase inhibitors, and polymerase inhibitors.
Analyzed complexities in drug synthesis, pharmacokinetics, and resistance development.
Provided comparative analyses of WHO-recommended drugs and those approved in various countries.
Identified significant antiviral resistance, particularly with M2 blockers, and to a lesser extent with NA and polymerase inhibitors.
Highlighted suboptimal pharmacokinetic profiles of many existing antiviral treatments as a barrier to effective therapy.
Emphasized the need for balanced strategies in antiviral development to ensure efficacy and global accessibility.

Abstract

SUMMARYInfluenza viruses remain a serious global health problem, causing annual epidemics and potential pandemics with significant morbidity and mortality. Antiviral therapy, particularly with direct-acting antivirals (DAAs), is a critical component of influenza control. This comprehensive review analyzes the current landscape of DAA drugs, with special attention paid to the complexity of synthesis, pharmacokinetic properties, and the development of antiviral resistance. We evaluated approved treatments, including neuraminidase (NA) inhibitors, viral RNA polymerase inhibitors, hemagglutinin (HA) inhibitors, and M2 ion channel blockers. We identify several critical obstacles to effective treatment: (i) the high genetic variability of influenza viruses, which facilitates the emergence of resistance, particularly in the case of M2 blockers (widespread) and, to a lesser but concerning extent, NA and polymerase inhibitors, both through natural evolution and selective pressure during drug treatment, and (ii) the suboptimal pharmacokinetic profiles of many existing drugs. This review provides a crucial framework for evaluating existing and investigational drugs for influenza, emphasizing the need to develop balanced therapeutic strategies that consider efficacy, resistance management, and global accessibility. The novelty of this review is a comprehensive comparative analysis of not only the drugs officially recommended by the WHO but also a wide range of other anti-influenza drugs approved in individual countries or under development. We have identified key comparative aspects that are discussed in detail here and are not always brought together in other reviews. The purpose of the article is to provide a generalized overview of the current state of knowledge, identify key trends and problems, and discuss future prospects without providing new primary data or experimental results.

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