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In Vivo Therapeutic Protection Against Influenza A (H1N1) Oseltamivir-Sensitive and Resistant Viruses by the Iminosugar UV-4

In Vivo Therapeutic Protection Against Influenza A (H1N1) Oseltamivir-Sensitive and Resistant Viruses by the Iminosugar UV-4

Eric J Stavale, Hong Vu, Aruna Sampath, Urban Ramstedt, Kelly L Warfield

PLoS One. 2015 Mar 18;10(3):e0121662.

PMID: 25786028

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP73465437	1-Deoxymannojirimycin hydrochloride		73465-43-7	Price

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