A review of neuraminidase inhibitor susceptibility in influenza strains

Abstract

Influenza human infections are considered as a persistent global public health issue. Whereas vaccination is important for prevention, given its limitations, antiviral therapy is at the forefront of treatment, while it also plays a significant role in prevention. Currently, two classes of drugs, adamantanes (M2 blockers) and neuraminidase inhibitors (NAIs), are available for treatment and chemoprophylaxis of influenza infections. Given the resistance patterns of circulating influenza strains, adamantanes are not currently recommended. The current review mainly focuses on the development of resistance to NAIs among A and B subtypes of influenza virus strains over the last 5 years. 'Permissive' drift mutations and reassortment of viral gene segments have resulted in NAI oseltamivir-resistant A/(H1N1) variants that rapidly became predominant worldwide in the period 2007-2009. However, the prevalence of antiviral resistance to NAI zanamivir remains relatively low. In addition, the recently developed NAIs, peramivir and laninamivir, while licensed in certain countries, are still under evaluation and only a few reports have described resistance to peramivir. Although in 2014, the majority of circulating human influenza viruses remains susceptible to all NAIs, the emergence of oseltamivir-resistant influenza variants that could retain viral transmissibility, highlights the necessity for enhanced epidemiological and microbiological surveillance and clinical assessment of antiviral resistance.

Reduction of Neuraminidase Activity Exacerbates Disease in 2009 Pandemic Influenza Virus-Infected Mice

“…Apart from this one mutation, the remaining mutations appeared to occur sporadically, and the general consensus sequence of the virus remained intact. None of these mutations have been associated with oseltamivir resistance or oseltamivir-related treatment (33,34). Furthermore, these mutations have not been shown to be associated with mouse adaptation or viral adaptation to a new host (35)(36)(37)(38)(39)(40)(41)(42)(43).…”

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

“…IAV is an enveloped virus which belongs to the Orthomyxoviridae family [10]. The genome is comprised of eight single-stranded RNA segments to encode total 10-13 proteins depending on the virus strain.…”

“…Some proteins are only expressed in the infected cells and not present in virion, for example nonstructural protein 1 (NS1), PB1-F2, PA-X and N40. Two gene segments are alternatively spliced to produce NS1/NEP and M1/M2proteins [10].…”

“…The viruses can also undergo reassortment of genetic segments to generate even greater variations and sometimes antigenic shift. These genetic variations are potential causes of epidemic and pandemic [10].…”

Amino acid interaction networks provide a new lens for therapeutic antibody discovery and anti-viral drug optimization

“…Finally, viral genomes are not static but continuously 'updated' in response to environmental cues. For example, prior to the 2009 H1N1 pandemic, circulating influenza strains required approximately three years to develop widespread resistance to oseltamivir, a small molecule, neuraminidase inhibitor [1]. This 'resistance challenge', which can be thought of as an arms race between host and pathogen, is especially true of RNAbased viruses, such as influenza, dengue, hepatitis C, and HIV, among others.…”