New drug-strategies to tackle viral-host interactions for the treatment of influenza virus infections

Abstract

The influenza virus (IV) is a highly contagious virus causing seasonal global outbreaks affecting annually up to 20% of the world's population and leading to 250,000-500,000 deaths worldwide. Current vaccines have variable effectiveness, and, in particular during a pandemic outbreak, they are probably not available in the amounts needed to protect the world population. Therefore we need effective small molecule drugs to combat an IV infection and that can be produced, in case of pandemic, rapidly and in large quantities. Unfortunately, natural occurring IV becomes more and more resistant to current anti-IV drugs. And thus, there is an urgent need for development of alternative agents with new mechanisms of action. This review provides an overview of the pharmacology and effectiveness of new anti-IV agents, focusing on inhibition mechanisms directed against virus-host interactions.

Target Virus or Target Ourselves for COVID-19 Drugs Discovery?―Lessons learned from anti-influenza virus therapies

“…New strategies to control emerging viruses, including their drugresistant mutants, such as SARS-CoV-2, are utmost needed. A new approach of targeting host factors for anti-pathogens emerged recently [15]. We have been working on this topic for more than a decade, mainly focusing on SUMOylation and other Ubiquitylation-like pathways because they both regulate cytokine signaling and viral proteins stabilities [16][17][18][19].…”

Influenza virus infection, interferon response, viral counter-response and apoptosis

“…After binding, virus particles are internalized by endocytosis [13]. Following the internalization, IAVs are transported to late endosomes where the acidic environment facilitates HA-mediated fusion of the viral and endosomal membrane, followed by the dissociation and degradation of M1 from 3 of 9 vRNPs [14,15].…”

The Host Cell ViroCheckpoint: Identification and Pharmacologic Targeting of Novel Mechanistic Determinants of Coronavirus-Mediated Hijacked Cell States

“…In contrast, targeting host cell proteins, especially at an early stage when viral hijacking of host mechanisms may still be reversible, may have more universal and longer term value because the same host factors may be required by multiple, potentially unrelated viral species and because host target proteins mutate far less rapidly than viral proteins, thereby limiting emergence of drug resistance (13). Unfortunately, pharmacologic targeting of host factors is more commonly associated with toxicity, thereby limiting clinical application of many drugs identified as potential anti-viral agents in vitro, for instance, with anti-CoV drugs EC 50 markedly exceeding their maximum tolerated serum concentration (C max ) (5).…”