Current Advances in Anti-Influenza Therapy

Abstract

Every year, influenza epidemics cause numerous deaths and millions of hospitalizations, but the most frightening effects are seen when new strains of the virus emerge from different species (e.g. the swine-origin influenza A/H1N1 virus), causing world-wide outbreaks of infection. Several antiviral compounds have been developed against influenza virus to interfere with specific events in the replication cycle. Among them, the inhibitors of viral uncoating (amantadine), nucleoside inhibitors (ribavirin), viral transcription and neuraminidase inhibitors (zanamivir and oseltamivir) are reported as examples of traditional virus-based antiviral strategies. However, for most of them the efficacy is often limited by toxicity and the almost inevitable selection of drug-resistant viral mutants. Thus, the discovery of novel anti-influenza drugs that target general cell signaling pathways essential for viral replication, irrespective to the specific origin of the virus, would decrease the emergence of drug resistance and increase the effectiveness towards different strains of influenza virus. In this context, virus-activated intracellular cascades, finely regulated by small changes in the intracellular redox state, can contribute to inhibit influenza virus replication and pathogenesis of virus-induced disease. This novel therapeutic approach involves advanced cell-based antiviral strategies. In this review current advances in the anti-influenza therapy for both traditional virus-based antiviral strategies as well as for alternative cell-based antiviral strategies are described focusing on the last 10 years. Anti-influenza compounds are classified on the basis of their chemical structure with a special attention to describe their synthetic pathways and the corresponding structure activity relationships.

Influenza neuraminidase

“…Peramivir was briefly licensed for emergency use during the swine-origin H1N1 epidemic in an injectable formulation for patients on ventilators and is currently completing clinical trials, and several other backbones are being tested as well as further derivatives of zanamivir. Several recent reviews describe these new developments 3,5,6,66–69 .…”

Structural Insights on the Potential Significance of the Twin Asn-Residue Found at the Base of the Hemagglutinin 2 Stalk in All Influenza A H1N1 Strains: A Computational Study with Clinical Implications

“…At the moment, there are several proposed anti-influenza therapies based on varying strategies (Palese and GarciaSastre 2002;Saladino et al, 2010). Based on our results, we propose that designing influenza vaccines and antiviral strategies that target the twin Asn-residue could have the potential to be another anti-influenza strategy.…”

Cellular and Immunological Regulation of Viral Myocarditis

“…Although, directly targeting viruses has been successful in controlling viral diseases, it suffers from some serious weaknesses, including failure to eliminate chronic viral myocarditis, narrow spectrum of action, and the inherent capacity to force outgrowth of drug resistance mutations (Tan et al, 2007). Thus, the discovery of novel antiviral targets, host cell-based antiviral agents is a more promising approach and deserves more attention (Saladino et al, 2010). At the cellular level, studies have shown that host cell phospho-proteins essential for viral replication, are potentially targetable [ (Marchant 2009) reviewed in ].…”