Detection and management of antiviral resistance for influenza viruses

Abstract

Neuraminidase inhibitors (NAIs) are first‐line agents for the treatment and prevention of influenza virus infections. As for other antivirals, the development of resistance to NAIs has become an important concern particularly in the case of A(H1N1) viruses and oseltamivir. The most frequently reported change conferring oseltamivir resistance in that viral context is the H275Y neuraminidase mutation (N1 numbering). Recent studies have shown that, in the presence of the appropriate permissive mutations, the H275Y variant can retain virulence and transmissibility in some viral backgrounds. Most oseltamivir‐resistant influenza A virus infections can be managed with the use of inhaled or intravenous zanamivir, another NAI. New NAI compounds and non‐neuraminidase agents as well as combination therapies are currently in clinical evaluation for the treatment for severe influenza infections.

A Novel Endonuclease Inhibitor Exhibits Broad-Spectrum Anti-Influenza Virus Activity In Vitro

“…In this report, we have characterized the activity of this compound in a variety of assays and platforms: the plaque number reduction, virus yield (TCID 50 ) reduction, and cell viability assays (5,59). Our results across 36 influenza A and B viruses demonstrate the breadth of anti-influenza activity of RO-7.…”

“…Two classes of virus protein-specific antiviral drugs are available for treating influenza, but of these, the drugs in the first class, the adamantanes (amantadine hydrochloride [amantadine] and rimantadine), are largely ineffective because of widespread virus resistance (5). The drugs in the second class, the neuraminidase (NA) inhibitors (NAIs), are currently the only drugs recommended for prophylaxis and treatment of influenza virus infection (6).…”

“…The drugs in the second class, the neuraminidase (NA) inhibitors (NAIs), are currently the only drugs recommended for prophylaxis and treatment of influenza virus infection (6). Until 2007, a low (Ͻ0.3%) frequency of circulation of NAIresistant influenza viruses was reported (7), but during the 2007-2009 seasons, naturally occurring oseltamivir-resistant A(H1N1) viruses with an H274Y NA substitution (N2 numbering is used here and throughout the text) were detected with high prevalence (approximately 90%) worldwide (5,8). This lineage was later supplanted by the novel swine-origin pandemic A(H1N1)pdm09 influenza virus, which was susceptible to oseltamivir (5,9).…”

“…Until 2007, a low (Ͻ0.3%) frequency of circulation of NAIresistant influenza viruses was reported (7), but during the 2007-2009 seasons, naturally occurring oseltamivir-resistant A(H1N1) viruses with an H274Y NA substitution (N2 numbering is used here and throughout the text) were detected with high prevalence (approximately 90%) worldwide (5,8). This lineage was later supplanted by the novel swine-origin pandemic A(H1N1)pdm09 influenza virus, which was susceptible to oseltamivir (5,9). Antiviral surveillance reported a low (0.1% to 3%) frequency of biologically fit oseltamivir-resistant A(H1N1)pdm09 viruses between 2009 and 2015, but the possibility of the establishment and spread of such strains remains a major concern (10,11).…”

The PA Endonuclease Inhibitor RO-7 Protects Mice from Lethal Challenge with Influenza A or B Viruses

“…The development of NAI resistance is of critical concern. During the 2007-2009 influenza seasons, naturally occurring oseltamivirresistant A (H1N1) viruses with an H274Y NA substitution (N2 numbering) appeared and predominated (with approximately 90% resistance being detected) among circulating viruses of this subtype (13,14). The incidence of NAI resistance among seasonal influenza viruses remains low (0.1 to 3%) (15,16).…”