Baloxavir Marboxil Treatment of Nude Mice Infected With Influenza A Virus

Abstract Background Immunocompromised patients infected with influenza virus require prolonged treatment with neuraminidase inhibitors, because these patients are not able to eradicate the virus from the respiratory tract, leading to the emergence of drug-resistant mutant viruses. Methods In this study, we examined the efficacy of baloxavir marboxil in nude mice that were immunologically deficient. Results Daily treatment with a suboptimal dose of baloxavir marboxil increased the survival time of the virus-infected nude mice but did not clear the virus from their respiratory organs, resulting in gradual body weight loss after termination of treatment. Conclusions Despite the prolonged baloxavir marboxil treatment, few resistant mutants were detected.

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Solution NMR structure of the V27A drug resistant mutant of influenza A M2 channel

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2010.09.008 ◽

2010 ◽

Vol 401 (1) ◽

pp. 58-63 ◽

Cited By ~ 72

Author(s):

Rafal M. Pielak ◽

James J. Chou

Keyword(s):

Influenza A ◽

Resistant Mutant ◽

Nmr Structure ◽

Solution Nmr ◽

Drug Resistant ◽

Drug Resistant Mutant

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Discovery of Novel Dual Inhibitors of the Wild-Type and the Most Prevalent Drug-Resistant Mutant, S31N, of the M2 Proton Channel from Influenza A Virus

Journal of Medicinal Chemistry ◽

10.1021/jm301538e ◽

2013 ◽

Vol 56 (7) ◽

pp. 2804-2812 ◽

Cited By ~ 68

Author(s):

Jizhou Wang ◽

Chunlong Ma ◽

Jun Wang ◽

Hyunil Jo ◽

Belgin Canturk ◽

...

Keyword(s):

Influenza A Virus ◽

Influenza A ◽

Resistant Mutant ◽

Proton Channel ◽

Drug Resistant ◽

Wild Type ◽

Drug Resistant Mutant ◽

Dual Inhibitors ◽

M2 Proton Channel

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Combination Therapy With Neuraminidase and Polymerase Inhibitors in Nude Mice Infected With Influenza Virus

The Journal of Infectious Diseases ◽

10.1093/infdis/jix606 ◽

2017 ◽

Vol 217 (6) ◽

pp. 887-896 ◽

Cited By ~ 23

Author(s):

Maki Kiso ◽

Tiago J S Lopes ◽

Seiya Yamayoshi ◽

Mutsumi Ito ◽

Makoto Yamashita ◽

...

Keyword(s):

Influenza Virus ◽

Combination Therapy ◽

Nude Mice ◽

Influenza A ◽

Neuraminidase Inhibitor ◽

Drug Resistant ◽

Neuraminidase Inhibitors ◽

Combination Therapies ◽

Survival Times ◽

Immunocompromised Hosts

Abstract Background Treatment of immunocompromised, influenza virus–infected patients with the viral neuraminidase inhibitor oseltamivir often leads to the emergence of drug-resistant variants. Combination therapy with compounds that target different steps in the viral life cycle may improve treatment outcomes and reduce the emergence of drug-resistant variants. Methods Here, we infected immunocompromised nude mice with an influenza A virus and treated them with neuraminidase (oseltamivir, laninamivir) or viral polymerase (favipiravir) inhibitors, or combinations thereof. Results Combination therapy for 28 days increased survival times compared with monotherapy, but the animals died after treatment was terminated. Mono- and combination therapies did not consistently reduce lung virus titers. Prolonged viral replication led to the emergence of neuraminidase inhibitor–resistant variants, although viruses remained sensitive to favipiravir. Overall, favipiravir provided greater benefit than neuraminidase inhibitors. Conclusions Collectively, our data demonstrate that combination therapy in immunocompromised hosts increases survival times, but does not suppress the emergence of neuraminidase inhibitor–resistant variants.

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Interaction between finger millet (Eleusine coracana) genotypes and drug-resistant mutants ofAzospirillum brasilensein calcareous soil

The Journal of Agricultural Science ◽

10.1017/s0021859600042088 ◽

1984 ◽

Vol 102 (3) ◽

pp. 521-529 ◽

Cited By ~ 10

Author(s):

R. Rai ◽

V. Prasad ◽

I. C. Shukla

Keyword(s):

Azospirillum Brasilense ◽

Finger Millet ◽

Nitrogenase Activity ◽

Resistant Mutant ◽

Eleusine Coracana ◽

Drug Resistant ◽

Mutant Strains ◽

Drug Resistant Mutant ◽

Uninoculated Control ◽

Resistant Mutants

SummaryAzospirillum brasilensewas treated with nitrosoguanidine and five drug-resistant mutant strains isolated. The effects of acriflavin on pre- and post-irradiation with u.v. light and the level of antibiotic resistance were studied. Variations in factors were found between the strains. Inoculation of finger millet withA. brasilenseand mutant strains led to significant increases in grain yield and nitrogenase activity compared with the uninoculated control, with significant strain x genotype interactions. Differential response of genotype and strain was noted on the protein and amino acid concentration of seeds.

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