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News 2021

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Neuraminidase inhibitors

Profile and generation of reduced neuraminidase inhibitor susceptibility in highly pathogenic avian influenza H7N9 virus from human cases in Mainland of China, 2016-2019

This study examined the drug resistance profile of 30 HPAI H7N9 isolates from Mainland of China (2016-2019) and also passaged an HPAI reassortant with NAIs for 10 passages …read more

In vitro profiling of laninamivir-resistant substitutions in N3 to N9 avian influenza virus neuraminidase subtypes and their association with in vivo susceptibility

This study profiled resistance to the anti-influenza drug laninamivir in AIVs with substitutions known to impart resistance to other NAIs. It was found that 10 substitutions that conferred resistance to all four NAIs tested. On the other hand, the remaining 26 NA substitutions were susceptible to at least one or more NAIs and showed for a small selection that in vitro data predicted in vivo behaviour …read more

Comparison of Household Transmission of Influenza Virus From Index Patients Treated With Baloxavir Marboxil or Neuraminidase Inhibitors: A Health Insurance Claims Database Study

This study concluded that Baloxavir may contribute to reduce the incidence of household transmission compared with oseltamivir, which is widely used for oral influenza treatment. In comparison between baloxavir and inhalants, a similar reduction was not shown and it might be due to unmeasured confounding by administration route differences …read more

Efficacy of oseltamivir compared with zanamivir in COPD patients with seasonal influenza virus infection: a randomized controlled trial

The results suggested that oseltamivir and zanamivir are effective in reducing body temperature, while oseltamivir led to better clinical improvement regarding influenza-like symptoms in patients with COPD …read more

Baloxivir Marboxil

Multiple polymerase acidic (PA) I38X substitutions in influenza A(H1N1)pdm09 virus permit polymerase activity and cause reduced baloxavir inhibition

This study provides a targeted approach for virus rescue and analysis of novel baloxavir marboxil reduced-susceptibility markers, supports the consideration of a broader range of these markers during antiviral surveillance and adds to the growing knowledge of baloxavir marboxil resistance profiles … read more

The antiviral effects of baloxavir marboxil against influenza A virus infection in ferrets

This animal study looks at baloxivir pharmacokinetics in ferrets, and also demonstrates effectiveness of baloxivir in reducing viral titres in both a prophylaxis or therapeutic model … read more

Detection of baloxavir resistant influenza A viruses using next generation sequencing and pyrosequencing methods

This study explores different methods of detection for baloxavir resistant variants …read more

Evaluation of Baloxavir Marboxil and Peramivir for the Treatment of High Pathogenicity Avian Influenza in Chickens

This study evaluated the impact of baloxavir and peramivir on treatment of chicken challenged with the highly pathogenic avian H5N6 HPAI virus and found improvements with both … read more

New Drug Discovery

Discovery of highly potent and selective influenza virus neuraminidase inhibitors targeting 150-cavity

Reports the design, synthesis and biological evaluation of a series of novel oseltamivir derivatives. 5c bearing a 4-(3-methoxybenzyloxy) benzyl group exhibited high potency against N1 and N1–H274Y mutant NAs … read more

Synthesis, inhibitory activity and oral dosing formulation of AV5124, the structural analogue of influenza virus endonuclease inhibitor baloxavir

This study describes the synthesis of structural analogues of cap-dependent endonuclease inhibitors, AV5124 and A5116 … read more

The clinically used serine protease inhibitor nafamostat reduces influenza virus replication and cytokine production in human airway epithelial cells and viral replication in mice

The findings from this study suggest that nafamostat may inhibit influenza virus replication in human airway epithelial cells and mouse lungs and reduce infection-induced airway inflammation by modulating cytokine production …read more

Clinical Trials and Case studies

Baloxavir treatment in adolescents with acute influenza: subgroup analysis from the CAPSTONE-1 trial

This study showed that baloxavir demonstrated clinical and virologic efficacy in otherwise healthy adolescents with acute influenza compared with placebo …read more

Duration of fever and symptoms in children after treatment with baloxavir marboxil and oseltamivir during the 2018-2019 season and detection of variant influenza A viruses with polymerase acidic subunit substitutions

This prospective, multicenter, non-randomized observational study assessed the duration of fever and symptoms of influenza A/H1N1pdm09 and A/H3N2 infected children < 19 years old treated with either baloxavir or oseltamivir …read more

Baloxavir treatment of oseltamivir-resistant influenza A/H1pdm09 in two immunocompromised patients

This study found that baloxavir/zanamivir combination therapy was effective in one patient, but persistent viral shedding was noted with baloxavir monotherapy in the other patient … read more

Antiviral News prepared by: Rubaiyea Farrukee, Postdoctoral Fellow at University of Melbourne, Australia