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Combinations of L-N(G)-monomethyl-arginine and oseltamivir against pandemic influenza A virus infections in mice.

Abstract L-N(G)-monomethyl-arginine (L-NMMA) is an experimental compound that suppresses nitric oxide production in animals. The compound was combined with oseltamivir to treat lethal influenza A/California/04/2009 (H1N1) pandemic virus infections in mice. Treatments were given twice a day for five days starting 4 h (oseltamivir, by oral gavage) or three days (L-NMMA, by intraperitoneal route; corresponding to the time previously reported for nitric oxide induction in the animals) after infection. Low doses of oseltamivir were used in order to demonstrate synergy or antagonism. Oseltamivir monotherapy protected 70% of mice from death at 1 mg/kg/day. L-NMMA (40 and 80 mg/kg/day) was ineffective alone in preventing mortality. Compared to oseltamivir treatment alone, L-NMMA combined with oseltamivir was synergistically effective (as evaluated by three-dimensional MacSynergy analysis), resulting in survival increases from 20 to 70% when 40 or 80 mg/kg/day of L-NMMA was combined with 0.3 mg/kg/day of oseltamivir, and from 70 to 100% survival increases when these doses were combined with 1 mg/kg/day of oseltamivir. These data demonstrate that a nitric oxide inhibitor such as L-NMMA has the potential to be beneficial when combined with oseltamivir in treating influenza virus infections.
PMID
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Authors

Mayor MeshTerms
Keywords

L-NMMA

influenza

mice

oseltamivir

synergy

Journal Title antiviral chemistry & chemotherapy
Publication Year Start




PMID- 28417640
OWN - NLM
STAT- In-Process
DA  - 20170418
LR  - 20170418
IS  - 2040-2066 (Electronic)
IS  - 0956-3202 (Linking)
VI  - 25
IP  - 1
DP  - 2017 Apr
TI  - Combinations of L-NG-monomethyl-arginine and oseltamivir against pandemic
      influenza A virus infections in mice.
PG  - 11-17
LID - 10.1177/2040206617691885 [doi]
AB  - L-NG-monomethyl-arginine (L-NMMA) is an experimental compound that suppresses
      nitric oxide production in animals. The compound was combined with oseltamivir to
      treat lethal influenza A/California/04/2009 (H1N1) pandemic virus infections in
      mice. Treatments were given twice a day for five days starting 4 h (oseltamivir, 
      by oral gavage) or three days (L-NMMA, by intraperitoneal route; corresponding to
      the time previously reported for nitric oxide induction in the animals) after
      infection. Low doses of oseltamivir were used in order to demonstrate synergy or 
      antagonism. Oseltamivir monotherapy protected 70% of mice from death at 1
      mg/kg/day. L-NMMA (40 and 80 mg/kg/day) was ineffective alone in preventing
      mortality. Compared to oseltamivir treatment alone, L-NMMA combined with
      oseltamivir was synergistically effective (as evaluated by three-dimensional
      MacSynergy analysis), resulting in survival increases from 20 to 70% when 40 or
      80 mg/kg/day of L-NMMA was combined with 0.3 mg/kg/day of oseltamivir, and from
      70 to 100% survival increases when these doses were combined with 1 mg/kg/day of 
      oseltamivir. These data demonstrate that a nitric oxide inhibitor such as L-NMMA 
      has the potential to be beneficial when combined with oseltamivir in treating
      influenza virus infections.
FAU - Smee, Donald F
AU  - Smee DF
AD  - Department of Animal, Dairy and Veterinary Sciences, Institute for Antiviral
      Research, Utah State University, Logan, UT, USA.
FAU - Dagley, Ashley
AU  - Dagley A
AD  - Department of Animal, Dairy and Veterinary Sciences, Institute for Antiviral
      Research, Utah State University, Logan, UT, USA.
FAU - Tarbet, E B
AU  - Tarbet EB
AD  - Department of Animal, Dairy and Veterinary Sciences, Institute for Antiviral
      Research, Utah State University, Logan, UT, USA.
LA  - eng
PT  - Journal Article
DEP - 20170321
PL  - England
TA  - Antivir Chem Chemother
JT  - Antiviral chemistry & chemotherapy
JID - 9009212
OTO - NOTNLM
OT  - L-NMMA
OT  - influenza
OT  - mice
OT  - oseltamivir
OT  - synergy
EDAT- 2017/04/19 06:00
MHDA- 2017/04/19 06:00
CRDT- 2017/04/19 06:00
AID - 10.1177/2040206617691885 [doi]
PST - ppublish
SO  - Antivir Chem Chemother. 2017 Apr;25(1):11-17. doi: 10.1177/2040206617691885. Epub
      2017 Mar 21.

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