Global update on the susceptibility of human influenza viruses to neuraminidase inhibitors and status of novel antivirals, 2016–2017

2020

Sci Rep

The recommended antiviral drugs available for the treatment and prevention of influenza are neuraminidase inhibitors (NAIs). The aim of this study was to evaluate age-related clinical manifestations of adverse events (AEs) related to NAIs. FAERS and WebMD data were downloaded. The available NAIs selected for the analysis were oseltamivir, peramivir, zanamivir, and laninamivir. Disproportionality was analyzed using the proportional reporting ratio (PRR), the reporting odds ratio (ROR), and the information component (IC) methods. In total, 16729 AEs from 4598 patients and 575 AEs from 440 patients in the FAERS and WebMD, respectively, were included in the analysis. In the FAERS, AEs were more common among those who were younger (<19 years) for zanamivir, while for those who were older (>65 years) for peramivir. A disproportionality analysis showed that signals for vomiting and hallucinations were detected in younger patients given oseltamivir, while an abnormal hepatic function, cardiac failure, shock, and cardio-respiratory arrest were detected in older patients given peramivir. Psychiatric disorders were most common in younger and older patients, while gastrointestinal disorders were most common in adult given oseltamivir in the WebMD. Adverse symptoms related to NAIs varied and depended on the drugs used and the age of the patient.Influenza remains a major threat to public health in spite of the fact that an influenza vaccination has been shown to be effective for preventing infection. Every year worldwide, there are an estimated one billion cases of influenza, of which approximately three to five million are severe cases, resulting in 290,000 to 650,000 influenza-related deaths 1 . The recommended antiviral drugs available for the treatment and prevention of influenza are neuraminidase inhibitors (NAIs) 2 . After oseltamivir and zanamivir were approved by the U.S. Food and Drug Administration (FDA) in 1999, peramivir and laninamivir were developed for the prevention and control of influenza 3,4 , peramivir and laninamivir were developed for the prevention and control of influenza 5,6 . The two NAIs oseltamivir and zanamivir were widely used during the 2009 influenza A (H1N1) pandemic 7 . The most common adverse effects for oseltamivir are nausea, vomiting, and diarrhea 8 . Zanamivir can cause bronchospasm when administered by inhalation 4 . The U.S. FDA has recently approved the intravenous use of peramivir 5 , but has not approved laninamivir for use.Reports mostly from Japan in 2005 and 2006 suggested that oseltamivir increased the risk of neuropsychiatric symptoms such as delirium, hallucinations, and abnormal behaviors, and could lead to thoughts of self-injury or suicide in teenagers 9 . However, the U.S. FDA's pediatrics advisory committee concluded that the deaths were not related to oseltamivir, though twelve deaths were reported in Japanese children who were taking it in 2005 10 . In 2006, therefore, the U.S. FDA added a warning to the label of oseltamivir, drawing attention to the risk of developing n...

Section: Discussionmentioning

confidence: 99%

Assessment of adverse events related to anti-influenza neuraminidase inhibitors using the FDA adverse event reporting system and online patient reviews

Han

2020

Sci Rep

“…Neuraminidase Assay Kit (Applied Biosystems), according to the manufacturer's instructions. The susceptibility of influenza viruses to NAI was characterized using oseltamivir, zanamivir, and peramivir at concentrations that inhibited the NA activity by 50% (IC 50 ) as described previously [14].…”

Section: Na Inhibition Assaymentioning

confidence: 99%

Characterization of neuraminidase inhibitor-resistant influenza virus isolates from immunocompromised patients in the Republic of Korea

Lee

et al. 2020

Preprint

Background: The emergence of influenza viruses resistant to anti-influenza drugs is a threat to public health. The Korea Centers for Disease Control and Prevention operates the Korea Influenza and Respiratory Viruses Surveillance System (KINRESS) to monitor epidemic of influenza and Severe Acute Respiratory Infection (SARI) to identify mutated influenza viruses affecting drug resistance, pathogenesis, and transmission. Methods: Oropharyngeal swab samples were collected from KINRESS and SARI during the 2018-2019 season. The specimens confirmed influenza virus using real-time RT-PCR on inoculated MDCK cells. HA and NA sequences of the influenza viruses were analyzed for phylogeny and mutations. Neuraminidase inhibition and hemagglutination inhibition assays were utilized to characterize the isolates. Results: Two A(H1N1)pdm09 isolates harboring an H275Y substitution in the neuraminidase sequence were detected in patients with acute hematologic cancer. They had prolonged respiratory symptoms, with the virus present in the respiratory tract despite oseltamivir and peramivir treatment. Through the neuraminidase inhibition assay, both the viruses were found to be resistant to oseltamivir and peramivir, but not to zanamivir. Although hemagglutinin and neuraminidase phylogenetic analyses suggested that the two A(H1N1)pdm09 isolates were not identical, their antigenicity was similar to that of the 2018-19 influenza vaccine virus. Conclusions: Our data indicate the utility of monitoring influenza-infected immunocompromised patients in general hospitals for the early detection of emerging neuraminidase inhibitor-resistant viruses and maintaining continuous laboratory surveillance of patients with influenza-like illness in sentinel clinics to monitor the spread of such new variants. Finally, characterization of the virus can inform the assessment of risk for future epidemics and pandemics caused by drug-resistant influenza viruses.

Journal of Heterocyclic Chem

“…NAIs can prevent virus release by inhibiting the influenza NA, resulting in aggregation of viruses at the cell surface . However, because of the rapid emergence of drug resistant virus , new anti‐influenza agents should be designed and synthesized with chemical characteristics clearly different from those of existing agents .…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Novel 1,2,4‐Triazole‐3‐thione Derivatives as Influenza Neuraminidase Inhibitors

Liu

Xiao

et al. 2019

A series of 1,2,4‐triazole‐3‐thione derivatives (6a–6t) were synthesized and evaluated against influenza viruses (H1N1) neuraminidase (NA) in vitro. Eighteen compounds exhibited inhibitory potency with IC50 values ranging from 14.68 ± 0.49 to 39.85 ± 4.23 μg/mL. Among them, compounds 6e and 6h showed significant inhibitory activity with IC50 values of 14.97 ± 0.70 and 14.68 ± 0.49 μg/mL, respectively. Structure activity relationships were established. Molecular docking studies were performed to understand the binding interaction between active compounds and NA.