Searching for effective antiviral small molecules against influenza A virus: A patent review

41 p.-6 fig.Introduction Despite the current interest caused by SARS-Cov-2, influenza continues to be one of the most serious health concerns, with an estimated 1 billion cases of influenza across the globe, including 3-5 million severe cases and 290,000-650,000 deaths worldwide.Areas covered This manuscript reviews the efforts made in the development of small molecules for the treatment of influenza virus, primarily focused on patent applications in the last five years. Attention is paid to compounds targeting key functional viral proteins, such as the M2 channel, neuraminidase, and hemagglutinin, highlighting the evolution toward novel ligands and scaffolds motivated by the emergence of resistant strains. Finally, the discovery of compounds against novel viral targets, such as the RNA-dependent RNA polymerase, is discussed.Expert opinion The therapeutic potential of antiviral agents is limited by the increasing presence of resistant strains. This should encourage research on novel strategies for therapeutic intervention. In this context, the discovery of arbidol and JNJ7918 against hemagglutinin, and current efforts on RNA-dependent RNA polymerase have disclosed novel opportunities for therapeutic treatment. Future studies should attempt to expand the therapeutic arsenal of anti-flu agents, often in combined therapies, which might be relevant to prevent future health challenges caused by influenza virus.This work was supported by the Spanish Ministerio de Economia y Competitividad (MINECO, SAF2017-88107-R; MDM2017-0767; AEI/FEDER UE), and the Generalitat de Catalunya (2017SGR1746)Peer reviewe