Seasonal and pandemic influenza are the two faces of respiratory infections caused by influenza viruses in humans. Influenza virus infection may result in pneumonia and acute respiratory failure, frequently complicated by bacterial coinfection[1]. Baloxavir marboxil is a small molecule inhibitor of the cap-dependent endonuclease of influenza A and B viruses. Baloxavir marboxil is a prodrug that is metabolised to an active form (known as S‐033447) which is highly effective at inhibiting a number of different influenza A and B viruses in vitro[2]. In a mouse model of infection, a single dose of Baloxavir marboxil was found to reduce viral load by 2 logs and reduced mortality compared to mice being treated with oseltamivir. In a phase II study of S‐033188, patients with uncomplicated influenza were randomised to three different doses (10 mg, 20 mg and 40 mg) and compared to placebo. All three doses resulted in significant reductions in time to alleviation of symptoms and reduced virus titres at 24 and 48 hours post‐treatment compared to placebo[2].
Baloxavir marboxil/玛巴洛沙韦 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Madin-Darby canine kidney (MDCK) cells
0.01–1000 nM
2–3 days
Assess virus sensitivity to baloxavir acid and determine IC50 values
J Infect Dis. 2020 Apr 27;221(10):1699-1702.
MDCK-SIAT1 cells
0.6 nM
24 hours
To evaluate the inhibitory effect of Baloxavir on influenza viruses, results showed significant inhibition of influenza virus by Baloxavir.
mBio. 2022 Aug 30;13(4):e0105622.
Madin-Darby canine kidney (MDCK) cells
4 nM
24 hours
To evaluate the inhibitory effect of BXA on A(H7N9) virus replication, results showed that BXA at 4 nM significantly reduced virus titers by 1.5-2.8 log.
Sci Rep. 2019 Mar 5;9(1):3466.
Baloxavir marboxil/玛巴洛沙韦 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
BALB/c mice
Lethal influenza virus A/PR/8/34 infection model
Oral gavage
0.5, 1.5, 15 or 50 mg/kg
Twice daily for 5 days
To evaluate the efficacy of delayed oral dosing (96 h post-infection) of baloxavir marboxil alone or in combination with oseltamivir phosphate in a lethal influenza virus infection Mice model. Results showed that baloxavir marboxil monotherapy (15 or 50 mg/kg twice daily) significantly and dose-dependently reduced virus titre 24 h after administration and completely prevented mortality, whereas oseltamivir phosphate monotherapy was less effective. Combination therapy (baloxavir marboxil 0.5 mg/kg + oseltamivir phosphate 10 mg/kg) provided additional efficacy compared with monotherapy in terms of virus-induced mortality, elevation of cytokine/chemokine levels, and pathological changes in the lung.
J Antimicrob Chemother. 2019 Mar 1;74(3):654-662
BALB/c mice
H5N1 highly pathogenic avian influenza virus infection model
Oral gavage
0.5, 5, or 50 mg/kg
Twice daily for 1 or 5 days
To evaluate the therapeutic effects of BXM on H5N1 highly pathogenic avian influenza virus infection, results showed that BXM significantly reduced viral titers and improved survival rates
Viruses. 2022 Jan 8;14(1):111
BALB/c mice
Highly pathogenic H7N9 virus infection model
Oral
1.5, 15, or 50 mg/kg
Once or twice daily for 5 days
To evaluate the therapeutic efficacy of baloxavir marboxil in mice infected with highly pathogenic H7N9 virus. Results showed that a single 15 mg/kg dose was sufficient to protect mice, and 5-day treatment significantly suppressed virus replication in respiratory organs.
Viruses. 2019 Nov 15;11(11):1066
Ferrets
Influenza A virus-infected ferret model
Oral
10 and 30 mg/kg
Twice daily for 1 day
To evaluate the antiviral effects of baloxavir marboxil against influenza A virus infection. Results showed that baloxavir marboxil significantly reduced virus titers and improved body temperature changes when administered at Day 1 post-infection.
Influenza Other Respir Viruses. 2020 Nov;14(6):710-719
Nude mice (BALB/c-nu/nu)
Immunocompromised Mice model infected with influenza virus
Oral
10 mg/kg
Once daily for 28 days
Evaluate therapeutic efficacy in immunocompromised hosts, prolonged survival time but failed to clear the virus
J Infect Dis. 2020 Apr 27;221(10):1699-1702.
Ferrets
Influenza virus infection model
Subcutaneous injection
4 mg/kg
Single dose
To evaluate the efficacy of Baloxavir alone or in combination with Oseltamivir in treating influenza virus infection, results showed that combination therapy reduced the selection of resistant viruses.
mBio. 2022 Aug 30;13(4):e0105622.
BALB/c mice
A/Anhui/1/2013 (H7N9) lethal infection model
Oral
5 and 50 mg/kg
Twice a day for 5 days
To evaluate the protective efficacy of BXM against A(H7N9) lethal infection, results showed that BXM at 5 and 50 mg/kg completely protected mice from lethal infection and significantly reduced lung virus titers by 2-3 log.
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