- |||||||||| Xofluza (baloxavir marboxil) / Roche
P4 data, Journal, Adverse events, Real-world evidence, Real-world: A real-world disproportionality analysis of Baloxavir Marboxil: post-marketing pharmacovigilance data. (Pubmed Central) - Sep 5, 2024
Compared to baloxavir's FDA label, some new PTs emerged, with the top 10 being pneumonia, loss of consciousness, rhabdomyolysis, seizure, altered state of consciousness, hepatic function abnormal, delirium, depressed level of consciousness, encephalopathy and cardio-respiratory arrest. In clinical application of baloxavir, attention should be paid to the new AE signals in addition to the those recorded in the labels, so as to ensure the safety of the patients.
- |||||||||| Relenza (zanamivir) / GSK, Vaxart, Xofluza (baloxavir marboxil) / Roche
Journal: Genotypic and phenotypic susceptibility of emerging avian influenza A viruses to neuraminidase and cap-dependent endonuclease inhibitors. (Pubmed Central) - Aug 12, 2024
The frequencies of NA or PA substitutions associated with reduced inhibition (RI) or highly reduced inhibition (HRI) by NA inhibitors (NAIs) (oseltamivir, zanamivir) or a cap-dependent endonuclease inhibitor (baloxavir) were low: 0.60% (137/22,713) and 0.62% (126/20,347), respectively...PA-E199A/D in A(H7Nx) and A(H9N2) viruses caused a 2- to 4-fold decrease in EC50 (close to the borderline for RI) and should be closely monitored. Our data indicate antiviral susceptibility is high among avian influenza A viruses with pandemic potential and present novel markers of resistance to existing antiviral interventions.
- |||||||||| Journal: Antiviral susceptibility of SARS-CoV-2 and influenza viruses from 3 co-infected pediatric patients. (Pubmed Central) - Aug 10, 2024
We evaluated the susceptibility of SARS-CoV-2 against RNA-dependent RNA polymerase inhibitors (remdesivir and molnupiravir) and 3C-like protease inhibitors (nirmatrelvir and ensitrelvir), and that of influenza viruses against neuraminidase inhibitors (oseltamivir, peramivir, zanamivir, and laninamivir) and the cap-dependent endonuclease inhibitor baloxavir...The patients were treated with anti-influenza drugs and did not develop severe symptoms despite the co-infection. Since SARS-CoV-2 and influenza viruses continue to evolve, continuous monitoring of their circulation remains essential to assess public health measures and support clinical management.
- |||||||||| Xofluza (baloxavir marboxil) / Roche
Journal: Influenza C virus susceptibility to antivirals with different mechanisms of action. (Pubmed Central) - May 2, 2024
However, these three inhibitors displayed comparable activity (EC50 8-22 nM) against type C viruses from six lineages. Banana lectin and a monoclonal antibody, YA3, targeting the hemagglutinin-esterase protein effectively neutralized some, but not all, type C viruses.
- |||||||||| Xofluza (baloxavir marboxil) / Roche, Shionogi
Journal: Discovery of a Macrocyclic Influenza Cap-Dependent Endonuclease Inhibitor. (Pubmed Central) - Feb 23, 2024
Despite their high antiviral potency, drug-resistant variants have been observed in clinical trials. Herein, we report a novel CEN inhibitor 8 with a delicately designed macrocyclic scaffold that exhibits a significantly smaller shift of inhibitory activity toward baloxavir-resistant variants.
- |||||||||| Journal: Identification of tanshinone I as cap-dependent endonuclease inhibitor with broad-spectrum antiviral effect. (Pubmed Central) - Dec 25, 2023
Tanshinones, especially tanshinone I, were identified as a cap-dependent endonuclease inhibitor with broad-spectrum antiviral effects on negative-stranded, segmented RNA viruses including bandavirus, orthomyxovirus, and arenavirus from natural products, implying an important resource of candidate antivirals from the traditional Chinese medicines. This study supplies novel candidate antivirals for the negative-stranded, segmented RNA virus and highlights the endonuclease involved in the cap-snatching process as a reliable broad-spectrum antiviral target.
- |||||||||| Xofluza (baloxavir marboxil) / Roche, Shionogi
Preclinical, Journal: Prophylactic Treatment with Baloxavir Protects Mice from Lethal Infection with Influenza A and B Viruses. (Pubmed Central) - Nov 29, 2023
In this model, baloxavir acid maintained significant prophylactic effects against influenza A and B virus infections when the plasma concentration at the time of infection was at least 0.88 and 3.58 ng/mL, respectively. The significant prophylactic efficacy observed in our mouse model suggests the potential utility of baloxavir marboxil for prophylaxis against influenza in humans.
- |||||||||| ZX-7101A / Zenshine Pharma, Xofluza (baloxavir marboxil) / Roche, Shionogi
Journal: PA-E18G substitution in influenza A virus confers resistance to ZX-7101, a cap-dependent endonuclease inhibitor. (Pubmed Central) - Aug 14, 2023
The CEN inhibitor, baloxavir marboxil (BXM), was approved in Japan and the US in 2018 and several other countries subsequently...Herein, we comprehensively characterized the in vitro and in vivo antiviral activities of ZX-7101A, an analogue of BXM...Reverse genetic and sequencing analysis demonstrated that a single E18G substitution in the PA subunit contributed to the reduced susceptibility to both ZX-7101 and BXA. Taken together, our results not only characterized a new CEN inhibitor of IAV but also identified a novel amino acid substitution responsible for CEN inhibitor resistance, which provides critical clues for future drug development and drug resistance surveillance.
- |||||||||| Xofluza (baloxavir marboxil) / Roche, Shionogi
Journal: Structure-activity relationship studies of anti-bunyaviral cap-dependent endonuclease inhibitors. (Pubmed Central) - Mar 2, 2023
This led us to screen carbamoyl pyridone bicycle (CAB) compounds, which compose a series of baloxavir acid (BXA) derivatives, against lymphocytic choriomeningitis virus (LCMV) and Junin virus (JUNV) among the bunyaviruses...The SAR results are discussed using a binding model of 9d in the active center of the known LCMV CEN crystal structure. These compounds show promise as broad-spectrum anti-bunyavirus therapeutics, given their relatively favorable metabolic stability and PK profiles.
- |||||||||| Xofluza (baloxavir marboxil) / Roche, Shionogi
Review, Journal: Antiviral Potential of Natural Resources against Influenza Virus Infections. (Pubmed Central) - Nov 15, 2022
Natural products have made an important contribution to the development of new lead structures, particularly in the field of infectious diseases. Therefore, this article aims to review the research on the identification of novel lead structures isolated from natural resources suitable to treat influenza infections.
- |||||||||| ribavirin / Generic mfg.
Journal: Identification of cap-dependent endonuclease inhibitors with broad-spectrum activity against bunyaviruses. (Pubmed Central) - Sep 6, 2022
We screened compounds from our CEN inhibitor (CENi) library and identified specific structural compounds that are 100 to 1,000 times more active in vitro than ribavirin against bunyaviruses, including Lassa virus, lymphocytic choriomeningitis virus (LCMV), and Junin virus...In LCMV-infected mice, the compounds significantly decreased blood viral load, suppressed symptoms such as thrombocytopenia and hepatic dysfunction, and improved survival rates. These data suggest a potential broad-spectrum clinical utility of CENis for the treatment of both severe influenza and hemorrhagic diseases caused by bunyaviruses.
- |||||||||| Journal: Estimation of optimal antiviral stockpile for a novel influenza pandemic. (Pubmed Central) - Jul 8, 2022
This will depend not only on the cost of the drugs, but on factors difficult to anticipate, such as the transmissibility of the virus, the time needed for vaccine development, and (especially) the emergence of resistance. If this information can be estimated, our model can be used to obtain the optimum.
- |||||||||| Journal: Antiviral Treatments for Influenza. (Pubmed Central) - May 6, 2022
Efficacy and safety profile of neuraminidase inhibitors (oseltamivir, zanamivir, laninamivir, peramivir) and recently approved cap-dependent endonuclease inhibitor baloxavir marboxil are reported in literature, but still little information is available about special populations such as critically ill patients and patients with a history of chronic respiratory disease. Moreover, the emergence of strains with reduced or no susceptibility to current drugs is a matter of concern, suggesting the need of constant monitoring of viral variants.
- |||||||||| Xofluza (baloxavir marboxil) / Roche, Shionogi
Review, Journal: Drug update - Baloxavir marboxil: Latest entrant into the arena of pharmacotherapy of influenza. (Pubmed Central) - Apr 26, 2022
Baloxavir marboxil, the prodrug of baloxavir, is the latest addition to the family of anti-influenza drugs, and it received US-FDA approval on October 24, 2018. Baloxavir acts through a novel mechanism of inhibiting Cap-dependent endonuclease (CEN), the vital step in the transcription of viral RNA, and prevents further spread of the virus.
- |||||||||| Xofluza (baloxavir marboxil) / Roche, Shionogi
Review, Journal: Baloxavir Marboxil: An Original New Drug against Influenza. (Pubmed Central) - Jan 26, 2022
The drug is now in post-marketing pharmacovigilance phase, and its interest will be especially re-evaluated in the future during the annual flu outbreaks. It has been also introduced in a recent clinical trial against COVID-19 with favipiravir.
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