Abstract
Influenza is a major acute respiratory infection that causes mortality and morbidity worldwide. Two classes of conventional antivirals, M2 ion channel blockers and neuraminidase inhibitors, are mainstays in managing influenza disease to lessen symptoms while minimizing hospitalization and death in patients with severe influenza. However, the development of viral resistance to both drug classes has become a major public health concern. Vaccines are prophylaxis mainstays but are limited in efficacy due to the difficulty in matching predicted dominant viral strains to circulating strains. As such, other potential interventions are being explored. Since viruses rely on host cellular functions to replicate, recent therapeutic developments focus on targeting host factors involved in virus replication. Besides controlling virus replication, potential targets for drug development include controlling virus-induced host immune responses such as the recently suggested involvement of innate lymphoid cells and NADPH oxidases in influenza virus pathogenesis and immune cell metabolism. In this review, we will discuss the advancements in novel host-based interventions for treating influenza disease.
Highlights
Influenza remains a source of public health concern
Despite impaired Influenza A virus (IAV) internalization caused by ARCN1 depletion via siRNA [56, 58], it was not able to recapitulate through acute inhibition of COPI complex by pharmaceutical means [58]
Transportation of HA to the plasma membrane for viral budding was found to be inhibited by Histone deacetylase 6 (HDAC6). This data suggests that activation of HDAC6 by its stimulant could be a potential approach to anti-IAV therapy, despite HDAC6 stimulants still being under development
Summary
Influenza remains a source of public health concern. Influenza A virus (IAV) has been the cause of historical noxious pandemics, such as the Spanish flu 1918 H1N1, Asian flu H2N2 1957, Hong Kong H3N2 flu 1968, and more recently the pandemic of H1N1 2009 (Swine flu). Significant levels of resistance to both classes of drugs have been repeatedly reported [4, 5]. Novel Targets for Influenza Treatment resistance (up to 91%) to M2 blockers has been reported in H3N2 virus strain in American isolates [6]. IAV resistance to NA inhibitors has become an increasingly prevalent concern, with the recent highly fatal outbreak of influenza A(H1N1)pdm in India 2015 associated with oseltamivir drug resistance [8, 9]. A large cluster of influenza A(H1N1)pdm viruses in Japan was found to have increased oseltamivir and peramivir drug resistance [5]. Many recent studies have focused on the investigation of targeting host factors to control virus replication as well as modulate immune response, which we have previously evaluated [13]. We will discuss the latest studies (in the past 5 years) on the investigation of novel host-based approaches with potential for influenza treatment
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