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Effects Of Combinations Of Favipiravir (T-705) And Oseltamivir On Influenza A (H1n1, H3n2, And H5n1) Virus Infections In Mice, D F. Smee, B L. Hurst, M H. Wong, K W. Bailey, E B. Tarbet, John D. Morrey, Y Furuta
Effects Of Combinations Of Favipiravir (T-705) And Oseltamivir On Influenza A (H1n1, H3n2, And H5n1) Virus Infections In Mice, D F. Smee, B L. Hurst, M H. Wong, K W. Bailey, E B. Tarbet, John D. Morrey, Y Furuta
John D. Morrey
Favipiravir (T-705 [6-fluoro-3-hydroxy-2-pyrazinecarboxamide]) and oseltamivir were combined to treat influenza virus A/NWS/33 (H1N1), A/Victoria/3/75 (H3N2), and A/Duck/MN/1525/81 (H5N1) infections. T-705 alone inhibited viruses in cell culture at 1.4 to 4.3 µM. Oseltamivir inhibited these three viruses in cells at 3.7, 0.02, and 0.16 µM and in neuraminidase assays at 0.94, 0.46, and 2.31 nM, respectively. Oral treatments were given twice daily to mice for 5 to 7 days starting, generally, 24 h after infection. Survival resulting from 5 days of oseltamivir treatment (0.1 and 0.3 mg/kg/day) was significantly better in combination with 20 mg/kg of body weight/day of T-705 against …
Persistent West Nile Virus Associated With A Neurological Sequela In Hamsters Identified By Motor Unit Number Estimation, V Siddharthan, H Wang, N E. Motter, J O. Hall, R D. Skinner, R T. Skirpstunas, John D. Morrey
Persistent West Nile Virus Associated With A Neurological Sequela In Hamsters Identified By Motor Unit Number Estimation, V Siddharthan, H Wang, N E. Motter, J O. Hall, R D. Skinner, R T. Skirpstunas, John D. Morrey
John D. Morrey
To investigate the hypothesis that neurological sequelae are associated with persistent West Nile virus (WNV) and neuropathology, we developed an electrophysiological motor unit number estimation (MUNE) assay to measure the health of motor neurons temporally in hamsters. The MUNE assay was successful in identifying chronic neuropathology in the spinal cords of infected hamsters. MUNE was suppressed at days 9 to 92 in hamsters injected subcutaneously with WNV, thereby establishing that a long-term neurological sequela does occur in the hamster model. MUNE suppression at day 10 correlated with the loss of neuronal function as indicated by reduced choline acetyltransferase staining (R2 …
Alkoxyalkyl Esters Of 9-(S)-(3-Hydroxy-2-Phosphonomethoxypropyl) Adenine Are Potent And Selective Inhibitors Of Hepatitis B Virus (Hbv) Replication In Vitro And In Hbv Transgenic Mice In Vivo, John D. Morrey, B E. Korba, J R. Beadle, D L. Wyles, K Y. Hostetler
Alkoxyalkyl Esters Of 9-(S)-(3-Hydroxy-2-Phosphonomethoxypropyl) Adenine Are Potent And Selective Inhibitors Of Hepatitis B Virus (Hbv) Replication In Vitro And In Hbv Transgenic Mice In Vivo, John D. Morrey, B E. Korba, J R. Beadle, D L. Wyles, K Y. Hostetler
John D. Morrey
Alkoxyalkyl esters of acyclic nucleoside phosphonates have previously been shown to have increased antiviral activity when they are administered orally in animal models of viral diseases, including lethal infections with vaccinia virus, cowpox virus, ectromelia virus, murine cytomegalovirus, and adenovirus. 9-(S)-(3-Hydroxy-2-phosphonomethoxypropyl)adenine [(S)-HPMPA] was previously shown to have activity against hepatitis B virus (HBV) in vitro. To assess the effect of alkoxyalkyl esterification of (S)-HPMPA, we prepared the hexadecyloxypropyl (HDP), 15-methyl-hexadecyloxypropyl (15M-HDP), and octadecyloxyethyl (ODE) esters and compared their activities with the activity of adefovir dipivoxil in vitro and in vivo. Alkoxyalkyl esters of (S)-HPMPA were 6 to 20 times more …
Activity Of T-705 In A Hamster Model Of Yellow Fever Virus Infection In Comparison With That Of A Chemically Related Compound, T-1106, J G. Julander, K Shafer, D F. Smee, John D. Morrey, Y Furuta
Activity Of T-705 In A Hamster Model Of Yellow Fever Virus Infection In Comparison With That Of A Chemically Related Compound, T-1106, J G. Julander, K Shafer, D F. Smee, John D. Morrey, Y Furuta
John D. Morrey
Treatment with the nucleoside analog T-1106 was previously shown to be effective in a hamster model of yellow fever virus (YFV) disease, even though it had only slight activity in cell culture. In the study described in this report, the activity of T-705, a chemically related compound currently undergoing clinical trials for the treatment of influenza (FDANews 4:1, 2007), was tested against YFV in cell culture and in the hamster model. The antiviral efficacy of T-705 in cell culture occurred at a concentration of 330 µM, which was more than threefold lower than the concentration at which T-1106 had antiviral …
Effects Of Double Combinations Of Amantadine, Oseltamivir, And Ribavirin On Influenza A (H5n1) Virus Infections In Cell Culture And In Mice, D F. Smee, B L. Hurst, M H. Wong, K W. Bailey, John D. Morrey
Effects Of Double Combinations Of Amantadine, Oseltamivir, And Ribavirin On Influenza A (H5n1) Virus Infections In Cell Culture And In Mice, D F. Smee, B L. Hurst, M H. Wong, K W. Bailey, John D. Morrey
John D. Morrey
An amantadine-resistant influenza A/Duck/MN/1525/81 (H5N1) virus was developed from the low-pathogenic North American wild-type (amantadine-sensitive) virus for studying treatment of infections in cell culture and in mice. Double combinations of amantadine, oseltamivir (or the cell culture-active form, oseltamivir carboxylate), and ribavirin were used. Amantadine-oseltamivir carboxylate and amantadine-ribavirin combinations showed synergistic interactions over a range of doses against wild-type virus in Madin-Darby canine kidney (MDCK) cell culture, but oseltamivir carboxylate-ribavirin combinations did not. Primarily additive interactions were seen with oseltamivir carboxylate-ribavirin combinations against amantadine-resistant virus. The presence of amantadine in drug combinations against the resistant virus did not improve activity. The …