Relenza (zanamivir) / GSK, Vaxart - LARVOL DELTA

Global update on the susceptibilities of influenza viruses to neuraminidase inhibitors and the cap-dependent endonuclease inhibitor baloxavir, 2020-2023. (PubMed, Antiviral Res) - "This study describes a global analysis of the susceptibility of influenza viruses to neuraminidase (NA) inhibitors (NAIs, oseltamivir, zanamivir, peramivir, laninamivir) and the cap-dependent endonuclease inhibitor (CENI, baloxavir) for three periods (May to May for 2020-2021, 2021-2022 and 2022-2023)...For zoonotic viruses, 2.7% (3/111) contained substitutions, one each NA-H275Y, NA-S247N and NA-N295S, associated with RI/HRI NAI phenotypes, and none contained PA substitutions associated with RS to baloxavir. In conclusion, the great majority of seasonal and zoonotic influenza viruses remained susceptible to NAIs and CENI baloxavir."

Journal • Infectious Disease • Influenza • Novel Coronavirus Disease • Respiratory Diseases

Discovery of Novel Natural Inhibitors of H5N1 Neuraminidase Using Integrated Molecular Modeling and ADMET Prediction. (PubMed, Bioengineering (Basel)) - "In contrast, Zanamivir exhibited limited hydrophobic interactions, compromising its binding stability within the active site. These findings offer a rational foundation for further experimental validation and the development of next-generation NA inhibitors derived from natural sources."

Journal • Infectious Disease • Influenza • Respiratory Diseases

Absorption, distribution, metabolism, and excretion of an antiviral drug-Fc conjugate CD388 following subcutaneous administration of 14C-CD388 in the rat. (PubMed, Drug Metab Dispos) - "Catabolism of the Fc domain resulted in formation of metabolites containing the unmodified dimeric zanamivir plus linker. These data support the mode of action of CD388 and demonstrate that the conjugation of zanamivir to the Fc domain is stable, thereby enabling CD388 to maintain its potent antiviral activity."

Journal • Preclinical • Infectious Disease • Influenza • Respiratory Diseases

Screening kinase inhibitors identifies MELK as a prime target against influenza virus infections through inhibition of viral mRNA splicing. (PubMed, Front Microbiol) - "Finally, we demonstrated that combining OTS167 with zanamivir or oseltamivir resulted in additive antiviral activity. In conclusion, we identified MELK as a crucial host kinase that supports the influenza virus infection. OTS167, a pharmacological inhibitor of MELK currently undergoing phase II clinical trials for treating cancer, potently inhibits influenza virus infections in vitro and in mice, representing a promising lead for developing novel influenza antivirals."

Journal • Infectious Disease • Influenza • Oncology • Pneumonia • Respiratory Diseases • CDK1 • MELK

Swine influenza virus surveillance programme pilot to assess the risk for animal and public health, the Netherlands, 2022 to 2023. (PubMed, Euro Surveill) - "Phenotypically, no reduced susceptibility to existing antiviral drugs oseltamivir and zanamivir was found.ConclusionWe provided insights into swIAVs in pigs in the Netherlands, including antiviral susceptibility and antigenic differences. It highlighted occasional virus transmission between humans and pigs. Sharing swIAV data at a national level will be continued to reduce influenza burden in swine and support identification and characterisation of emerging swIAVs with zoonotic potential."

Journal • Infectious Disease • Influenza • Respiratory Diseases

FIFTY-YEAR ANALYSIS OF INFLUENZA VACCINE EFFECTIVENESS AND ANTIVIRAL USE PATTERNS THROUGH MACHINE LEARNING: IMPLICATIONS FOR PAEDIATRIC INFLUENZA MANAGEMENT (ESPID 2025) - "Data were stratified by virus subtypes, including Influenza A(H1N1), A(H3N2), and Influenza B, as well as by the use of major antivirals such as Amantadine, Rimantadine, Zanamivir, Oseltamivir, Peramivir, and Baloxavir...Conclusions/Learning Points This analysis highlights the dynamic nature of influenza vaccine effectiveness and antiviral medication consumption over five decades. The findings underscore the necessity of ongoing research, global surveillance, and adaptability in influenza prevention and treatment strategies to address changing epidemiological patterns, particularly in vulnerable populations such as children."

Machine learning • Infectious Disease • Influenza

Report on influenza viruses received and tested by the Melbourne WHO Collaborating Centre for Reference and Research on Influenza during 2023. (PubMed, Commun Dis Intell (2018)) - "The majority of A(H1N1)pdm09, A(H3N2) and influenza B viruses analysed at the Centre were found to be antigenically and genetically similar to the respective WHO recommended vaccine strains for the southern hemisphere in 2023. Of 5,531 samples tested for susceptibility to the neuraminidase inhibitors oseltamivir and zanamivir, seven A(H1N1)pdm09 viruses showed highly reduced inhibition against oseltamivir."

Journal • Infectious Disease • Influenza • Respiratory Diseases

Identification & genetic & virological characterisation of a human case of avian influenza A (H9N2) virus from Eastern India. (PubMed, Indian J Med Res) - "The virus was found to be sensitive to neuraminidase inhibitors oseltamivir and zanamivir. Interpretation & conclusions Systematic avian influenza surveillance in both birds and humans is required for the early detection of newly evolved viruses."

Journal • Infectious Disease • Influenza • Respiratory Diseases

Seroprevalence of anti-influenza antibodies in humans and characterization of seasonal influenza viruses isolated in Russia during the 2023-2024 flu season. (PubMed, Arch Virol) - "All of the tested isolates were susceptible to oseltamivir and zanamivir, including two A(H1N1)pdm09 strains with an NA-S247N substitution. Seroprevalence analysis showed that 60%, 54%, and 46% of the human blood samples tested were seropositive for the A(H3N2), A(H1N1)pdm09 and B/Victoria antigens from the 2022-2023 vaccine."

Journal • Infectious Disease • Influenza • Respiratory Diseases

How to manage antivirals in critically ill patients with Influenza? (PubMed, Clin Microbiol Infect) - "Neuraminidase inhibitors constitute the vast majority of antivirals currently prescribed for influenza. The most commonly prescribed NAI to date is oseltamivir. While its efficacy in non-severe cases of influenza is well established, the evidence for its efficacy in critically ill patients is based on less robust studies, as no randomised controlled trials have been conducted in this population. Limited data on oseltamivir pharmacokinetics is available in critically ill patients. The selection of A(H1N1)pdm09 resistant variants to oseltamivir is particularly problematic in critically-ill patients hospitalised in intensive care units. Data on other antivirals, including NAIs (i.e., zanamivir, peramivir and laninamivir) or baloxavir marboxil in critically ill patients are scarce. Further research is needed to develop new drugs and assess their efficacy in critically ill patients and to better assess the effect of oseltamivir in this population."

Journal • Review • Critical care • Infectious Disease • Influenza • Respiratory Diseases

A monoclonal anti-hemagglutinin stem antibody modified with zanamivir protects against both influenza A and B viruses. (PubMed, Proc Natl Acad Sci U S A) - "The MEDI8852-zanamivir conjugate extends the circulatory half-life of zanamivir, targets both influenza HA and NA, and shows enhanced antibody-dependent cellular cytotoxicity (ADCC) compared to MEDI8852 alone. The MEDI8852-zanamivir conjugate protected mice from a lethal (10 × LD50) challenge with influenza A and B viruses at a dose similar to that required for broadly neutralizing anti-NA antibodies, with the added advantage of simultaneously targeting NA (influenza A and B) and HA (influenza A)."

Journal • Infectious Disease • Influenza • Respiratory Diseases

Factors Associated with Antiviral Drug Use among Commercially Insured Children at High Risk for Complications of Influenza. (PubMed, J Pediatr) - "Despite national guidelines recommending that all children at high risk for influenza complications receive antiviral treatment, nearly half of these children at high-risk did not receive an antiviral in our study. We identify several factors associated with decreased antiviral treatment that may serve to inform future interventions aiming to improve the care of vulnerable children with influenza."

Journal • Asthma • Immunology • Infectious Disease • Influenza • Pediatrics • Pulmonary Disease • Respiratory Diseases

Drug-Fc conjugate CD388 targets influenza virus neuraminidase and is broadly protective in mice. (PubMed, Nat Microbiol) - "CD388 improves the antiviral activity of zanamivir, demonstrating potent, universal activity across influenza A and B viruses, including high pathogenicity and neuraminidase inhibitor resistant strains, a low potential for resistance development and potent efficacy in lethal mouse infection models. These results suggest that CD388 has the potential for universal prevention of influenza A and B in healthy and high-risk populations."

Journal • Preclinical • Infectious Disease • Influenza • Respiratory Diseases

Novel derivatives of thiohydantoin-containing tetrahydro-β-carboline possess activity against influenza virus at late stages of viral cycle without affecting viral neuraminidase. (PubMed, Arch Pharm (Weinheim)) - "Of the 23 compounds under investigation, 10 (43.5%) displayed a selectivity index (SI) of 10 or higher, their activity strongly exceeding that of the reference compound rimantadine...However, no direct inhibiting activity against viral neuraminidase has been demonstrated. The results obtained can be considered as a rationale for further structural optimization and study of this group as potential broad-range antivirals effective against influenza viruses."

Journal • Infectious Disease • Influenza • Respiratory Diseases

Antiviral Susceptibility of Influenza A(H5N1) Clade 2.3.2.1c and 2.3.4.4b Viruses from Humans, 2023-2024. (PubMed, Emerg Infect Dis) - "In the neuraminidase inhibition assay, all viruses displayed susceptibility to neuraminidase inhibitor antiviral drugs oseltamivir, zanamivir, peramivir, laninamivir, and AV5080...All viruses were susceptible to polymerase inhibitors baloxavir and tivoxavir and to polymerase basic 2 inhibitor pimodivir with 50% effective concentrations in low nanomolar ranges. Because drug-resistant viruses can emerge spontaneously or by reassortment, close monitoring of antiviral susceptibility of H5N1 viruses collected from animals and humans by using sequence-based analysis supplemented with phenotypic testing is essential."

Journal • Infectious Disease • Influenza • Respiratory Diseases

Evaluation of influenza antiviral prophylaxis for long-term care residents: a systematic review and meta-analysis. (PubMed, Clin Infect Dis) - "Oseltamivir or zanamivir could provide some benefit but low statistical power behind most estimates precluded definitive conclusions. Therefore, additional studies (RCTs) are needed to expand the evidence base and validate whether prophylaxis is beneficial in this setting."

Journal • Retrospective data • Infectious Disease • Influenza • Respiratory Diseases

Zanamivir alleviates ethanol intoxication through activating catalase. (PubMed, Toxicol Lett) - "Collectively, our work suggests that zanamivir should be repurposed for countering alcohol intoxication in clinic."

Journal • CAT

A Simple and Efficient Stereoselective Synthesis of a 2,3-Difluorosialic acid-based influenza virus neuraminidase inhibitor. (PubMed, Chemistry) - "We now report a simple approach for the exquisitely stereo-controlled introduction of the C-3 equatorial fluorine on Neu by incorporation of steric bulk at C-4. Through this method, we have elaborated a novel synthetic route that exclusively produces the potent anti-influenza drug candidate; 2,3-difluoro-zanamivir analogue with C-3 eq fluoride."

Journal • Infectious Disease • Influenza • Respiratory Diseases

Incidence of Severe Illness in Pediatric Influenza Outpatients Treated with Baloxavir or Neuraminidase Inhibitors. (PubMed, J Infect Chemother) - "Using a large, Japanese health insurance claims database, a lower rate of hospitalization was demonstrated in children aged 5-11 years with an influenza virus infection when treated with baloxavir vs neuraminidase inhibitors. Thus, single dose, oral baloxavir may reduce the incidence of severe illness in these patients."

Journal • Infectious Disease • Influenza • Pediatrics • Respiratory Diseases

In vitro neuraminidase inhibitory concentrations (IC50) of four neuraminidase inhibitors in the Japanese 2023-24 season: Comparison with the 2010-11 to 2022-23 seasons. (PubMed, J Infect Chemother) - "These results indicate that susceptibility to these four NAIs has been maintained across the three influenza types/subtypes over the past fourteen seasons in Japan."

Journal • Preclinical • Infectious Disease • Influenza • Respiratory Diseases

Pharmacologic background and clinical issue of anti-influenza drugs. (PubMed, Fukushima J Med Sci) - "Since 2000, rapid antigen detection kits and anti-influenza drugs have been used for the early diagnosis and treatment of influenza in Japan, respectively.　The main drugs available in clinical practice are the neuraminidase inhibitors oseltamivir, zanamivir, laninamivir, and peramivir, as well as the cap-dependent endonuclease inhibitor baloxavir marboxil.　Antiviral therapy with neuraminidase inhibitors has been practiced for many years, especially in Japan; it can shorten the febrile period and reduce complications.　Despite having similar structures, the pharmacologic background of neuraminidase inhibitors differs significantly, as reflected in their varying clinical efficacy.　Due to its inhibitory mechanism, baloxavir marboxil can rapidly reduce the viral load than neuraminidase inhibitors.　However, the duration of symptoms was similar after the administration of baloxavir marboxil and oseltamivir, and variants with reduced drug susceptibility have been detected in..."

Journal • Infectious Disease • Influenza • Pediatrics • Respiratory Diseases

A Pharmacoeconomic Study of Post-Exposure Prophylaxis Strategies for Influenza Virus Infections in Japan. (PubMed, Adv Ther) - "Baloxavir marboxil and oseltamivir are cost-effective prophylactic agents for flu from the perspective of healthcare costs in Japan. This strategy to select baloxavir marboxil or oseltamivir would be helpful to manage a formulary for post-exposure prophylaxis in Japan."

HEOR • Journal • Infectious Disease • Influenza • Respiratory Diseases

In persons exposed to influenza, zanamivir, oseltamivir, laninamivir, and baloxavir reduce symptomatic seasonal influenza. (PubMed, Ann Intern Med) - "2024;404:764-772. 39181596."

Journal • Infectious Disease • Influenza • Respiratory Diseases

Antiviral drug development by targeting RNA binding site, oligomerization and nuclear export of influenza nucleoprotein. (PubMed, Int J Biol Macromol) - "Current antiviral drugs such as oseltamivir, zanamivir, peramivir and baloxavir marboxil along with seasonal vaccines have limitations due to viral variability caused by antigenic drift and shift as well as the development of drug resistance...We discuss various strategies for targeting NP, including RNA binding, oligomerization, and nuclear export, and also consider the potential of NP-based vaccines. Overall, this review provides insights into recent developments and future perspectives on targeting influenza NP for antiviral therapies."

Journal • Review • Infectious Disease • Influenza • Respiratory Diseases

Update and narrative review of avian influenza (H5N1) infection in adult patients. (PubMed, Pharmacotherapy) - "This includes a cell-based vaccine approved by the FDA for people aged 6 months and older who are at higher risk of exposure to the H5N1 virus called Audenz...Neuraminidase inhibitors are the mainstay of the avian influenza treatment and includes oseltamivir, peramivir, and zanamivir. Baloxavir marboxil is a cap-dependent endonuclease inhibitor. This clinical review aims to highlight the background, epidemiology, clinical presentation, complications and current treatment and prevention strategies for avian influenza H5N1."

Journal • Review • Infectious Disease • Influenza • Respiratory Diseases