A5055306808- Influenza Virus Research Studies
- Respiratory viral infections research
- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- interferon and immune responses
- Immune Response and Inflammation
- Computational Drug Discovery Methods
- Animal Disease Management and Epidemiology
- Synthesis and biological activity
- Cytokine Signaling Pathways and Interactions
- Geriatric Care and Nursing Homes
- Virology and Viral Diseases
- Healthcare Education and Workforce Issues
- Immunotherapy and Immune Responses
- Antibiotics Pharmacokinetics and Efficacy
- Health and Well-being Studies
- Nutrition, Health and Food Behavior
- Research on Leishmaniasis Studies
- Consumer Perception and Purchasing Behavior
- Vitamin C and Antioxidants Research
- SARS-CoV-2 detection and testing
- Viral gastroenteritis research and epidemiology
- Diverse Scientific Research Studies
- Education and Learning Interventions
Shionogi (Japan)
2011-2025
Futaba (Japan)
2020-2025
Kanto Gakuin University
2024
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become established in the human population, making need to develop safe and effective treatments critical. We have developed small-molecule antiviral ensitrelvir, which targets 3C-like (3CL) protease of SARS-CoV-2. This study evaluated vitro vivo efficacy ensitrelvir compared with that another SARS-CoV-2 3CL PI, nirmatrelvir.
Baloxavir marboxil (formerly S-033188) is a first-in-class, orally available, cap-dependent endonuclease inhibitor licensed in Japan and the USA for treatment of influenza virus infection. We evaluated efficacy delayed oral with baloxavir combination neuraminidase mouse model lethal infection.The inhibitory potency acid (the active form marboxil) inhibitors was tested vitro. The therapeutic effects oseltamivir phosphate, or combinations thereof, were mice lethally infected A/PR/8/34;...
Influenza viruses cause seasonal outbreaks and pose a continuous pandemic threat. Although vaccines are available for influenza control, their efficacy varies each season vaccine novel virus manufactured using current technology will not be fast enough to mitigate the effect of first wave. Antivirals can effective against many different but have thus far been used extensively outbreak control. Baloxavir, recently licensed antiviral drug that targets endonuclease, has shown reduce shedding...
Abstract Background SARS-CoV-2 and COVID-19 remain a major global health challenge. We have discovered second-generation small molecule 3CL protease inhibitor S-892216 that is proceeding with phase 1 study in Japan. has potent antiviral activity addresses current treatment concerns of currently available antivirals regarding drug-drug interaction (DDI) safety. evaluated the therapeutic effect by using infected hamster model. In this study, virus titer lungs nasal turbinates (NT), lung...
Abstract Background S-892216 is a candidate for the treatment of COVID-19 that has 3CLpro inhibitory activity and antiviral activity. In this study, susceptibility was evaluated against SARS-CoV-2 with substitution associated reduced to other inhibitors, ensitrelvir nirmatrelvir. Additionally, in vitro selection conducted. Methods Reverse genetics-derived (rgSARS-CoV-2) substitutions including M49L E166V were generated using circular polymerase extension reaction (CPER) system The assessed...
Abstract Background Although aerosol virus transmission is the major route for SARS-CoV-2 and there remains a need to control spread with antivirals, prophylactic effect of pre-exposure antiviral treatments prevent be clarified. In previous report, we established hamster model (ESWI 2023, Nakashima et al.) (Figure 1). Here, administered ensitrelvir naive hamsters (contact) prior exposure shed by virus-infected (index) evaluated efficacy antivirals on infection.Figure 1Experimental Methods...
Abstract Background COVID-19 caused by SARS-CoV-2 remains a global public health concern. Although oral direct-acting antivirals for (such as molnupiravir, nirmatrelvir/ritonavir, ensitrelvir) were approved clinical use, there are concerns about drug-drug interactions (DDI) and safety, so development of new therapeutics is needed. In this study, we describe enzyme inhibitory antiviral activity S-892216, second-generation small molecular 3C-like protease (3CLpro) inhibitor. Methods The 3CLpro...
ABSTRACT We evaluated the efficacy of a single intravenous dose peramivir for treatment influenza B virus infection in ferrets and cynomolgus macaques present study. A (60 mg/kg body weight) given to on 1 day postinfection with significantly reduced median area under curve (AUC) titers (peramivir, 8.3 log 10 50% tissue culture infective doses [TCID 50 s]·day/ml; control, 10.7 TCID s·day/ml; P < 0.0001). Furthermore, nasal 2 receiving injection (30 mg/kg) AUCs temperature increase 60 were...
The small-molecule antiviral drug ensitrelvir targets the 3C-like protease of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study evaluated its inhibitory effect on viral replication in a delayed-treatment mouse model and investigated relationship between pharmacokinetic (PK) parameters pharmacodynamic (PD) effects. SARS-CoV-2 gamma-strain-infected BALB/c mice were orally treated with various doses starting 24 h post-infection. Effectiveness was determined 48 after first...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological cause of disease 2019 (COVID-19) and continues to be a major health concern worldwide. Strategies protect individuals at high risk COVID-19 are critical but currently largely unmet need. We evaluated oral antiviral drug ensitrelvir, which specifically targets SARS-CoV-2 3CL protease, for its efficacy as pre-exposure prophylactic treatment. Aged BALB/c mice were subcutaneously treated with various doses...
Although the prevalence of polymerase acidic (PA)/I38T strains influenza virus with reduced susceptibility to baloxavir acid is low, there a possibility emergence under selective pressure. Furthermore, may be transmitted between humans. We investigated in vivo efficacy and oseltamivir phosphate against A subtypes H1N1, H1N1pdm09, H3N2, PA/I38T substitution, at doses simulating human plasma concentrations. pharmacokinetic/pharmacodynamic analysis was performed strengthen validity findings...
Influenza remains a worldwide health concern. Antiviral drugs are considered as one of the useful options for its prevention complementary measure to vaccination. Baloxavir acid selectively inhibits cap-dependent endonuclease influenza viruses and exhibits marked viral titre reduction in patients. Here, we describe prophylactic potency baloxavir against lethal infection with A B mice. BALB/c mice were subcutaneously administered once suspension, or orally daily 10 days oseltamivir phosphate...
Abstract Background Baloxavir marboxil (BXM), the oral prodrug of baloxavir acid (BXA), greatly reduces virus titers as well influenza symptoms uncomplicated in patients. Objectives To investigate pharmacokinetic profiles BXA and its efficacy against A infection ferrets. Methods Ferrets were dosed orally with BXM (10 30 mg/kg twice daily for 1 day), oseltamivir phosphate (OSP) (5 2 days) or vehicle to measure antiviral effects OSP. The parameters was determined after single dosing BXM....
This study aimed to clarify factors that affect turnover intention of nurses in Japanese nursing homes (NHs).
Abstract Background Baloxavir marboxil (BXM) is a novel small molecule inhibitor of cap-dependent endonuclease that essential for influenza virus transcription and replication. In this study, pharmacokinetic profiles BXM baloxavir acid (BXA), an active form BXM, were first examined in ferrets, then the therapeutic effects against A infection compared with oseltamivir phosphate ferrets. Methods The plasma exposure BXA was after single oral administration at doses 10 30 mg/kg. concentrations...
Abstract Background Baloxavir acid (BXA), an active form of orally available prodrug baloxavir marboxil (BXM, formerly S-033188), is a novel small molecule inhibitor cap-dependent endonuclease (CEN) influenza A and B virus, was recently launched for the treatment acute uncomplicated with single dosing BXM (the trade name XOFLUZA™) in Japan March 2018. Here, we evaluated prophylactic efficacy BXA mice lethally infected virus. Methods T1/2 human more than 10 times longer that mice. Therefore,...