tetano
Editor, Senior Moderator
PLoS One. 2015 Mar 18;10(3):e0121662. doi: 10.1371/journal.pone.0121662. eCollection 2015.
[h=1]In Vivo Therapeutic Protection against Influenza A (H1N1) Oseltamivir-Sensitive and Resistant Viruses by the Iminosugar UV-4.[/h] Stavale EJ[SUP]1[/SUP], Vu H[SUP]1[/SUP], Sampath A[SUP]2[/SUP], Ramstedt U[SUP]2[/SUP], Warfield KL[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Our lead iminosugar analog called UV-4 or N-(9-methoxynonyl)-1-deoxynojirimycin inhibits activity of endoplasmic reticulum (ER) α-glucosidases I and II and is a potent, host-targeted antiviral candidate. The mechanism of action for the antiviral activity of iminosugars is proposed to be inhibition of ER α-glucosidases leading to misfolding of critical viral glycoproteins. These misfolded glycoproteins would then be incorporated into defective virus particles or targeted for degradation resulting in a reduction of infectious progeny virions. UV-4, and its hydrochloride salt known as UV-4B, is highly potent against dengue virus in vitro and promotes complete survival in a lethal dengue virus mouse model. In the current studies, UV-4 was shown to be highly efficacious via oral gavage against both oseltamivir-sensitive and -resistant influenza A (H1N1) infections in mice even if treatment was initiated as late as 48-72 hours after infection. The minimal effective dose was found to be 80-100 mg/kg when administered orally thrice daily. UV-4 treatment did not affect the development of protective antibody responses after either influenza infection or vaccination. Therefore, UV-4 is a promising candidate for further development as a therapeutic intervention against influenza.
PMID: 25786028 [PubMed - in process] Free full text
[h=1]In Vivo Therapeutic Protection against Influenza A (H1N1) Oseltamivir-Sensitive and Resistant Viruses by the Iminosugar UV-4.[/h] Stavale EJ[SUP]1[/SUP], Vu H[SUP]1[/SUP], Sampath A[SUP]2[/SUP], Ramstedt U[SUP]2[/SUP], Warfield KL[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Our lead iminosugar analog called UV-4 or N-(9-methoxynonyl)-1-deoxynojirimycin inhibits activity of endoplasmic reticulum (ER) α-glucosidases I and II and is a potent, host-targeted antiviral candidate. The mechanism of action for the antiviral activity of iminosugars is proposed to be inhibition of ER α-glucosidases leading to misfolding of critical viral glycoproteins. These misfolded glycoproteins would then be incorporated into defective virus particles or targeted for degradation resulting in a reduction of infectious progeny virions. UV-4, and its hydrochloride salt known as UV-4B, is highly potent against dengue virus in vitro and promotes complete survival in a lethal dengue virus mouse model. In the current studies, UV-4 was shown to be highly efficacious via oral gavage against both oseltamivir-sensitive and -resistant influenza A (H1N1) infections in mice even if treatment was initiated as late as 48-72 hours after infection. The minimal effective dose was found to be 80-100 mg/kg when administered orally thrice daily. UV-4 treatment did not affect the development of protective antibody responses after either influenza infection or vaccination. Therefore, UV-4 is a promising candidate for further development as a therapeutic intervention against influenza.
PMID: 25786028 [PubMed - in process] Free full text