tetano
Editor, Senior Moderator
Antiviral Res. 2013 Jun 29. pii: S0166-3542(13)00171-X. doi: 10.1016/j.antiviral.2013.06.014. [Epub ahead of print]
Inhibitory and combinatorial effect of diphyllin, a v-ATPase blocker, on influenza viruses.
Chen HW, Cheng JX, Liu MT, King K, Peng JY, Zhang XQ, Wang CH, Shresta S, Schooley RT, Liu YT.
Source
Division of Infectious Disease, School of Medicine, University of California San Diego. 9500 Gilman Drive, La Jolla, CA 92093, United Sates of America; Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology. 9420 Athena Circle, La Jolla, CA 92037, United States of America; School of Veterinary Medicine, National Taiwan University. No. 1, Sec. 4 Roosevelt Road, Taipei 10617, Taiwan.
Abstract
An influenza pandemic poses a serious threat to humans and animals. Conventional treatments against influenza include two classes of pathogen-targeting antivirals: M2 ion channel blockers (such as amantadine) and neuraminidase inhibitors (such as oseltamivir). Examination of the mechanism of influenza viral infection has shown that endosomal acidification plays a major role in facilitating the fusion between viral and endosomal membranes. This pathway has led to investigations on vacuolar ATPase (v-ATPase) activity, whose role as a regulating factor on influenza virus replication has been verified in extensive genome-wide screenings. Blocking v-ATPase activity thus presents the opportunity to interfere with influenza viral infection by preventing the pH-dependent membrane fusion between endosomes and virions. This study aims to apply diphyllin, a natural compound shown to be as a novel v-ATPase inhibitor, as a potential antiviral for various influenza virus strains using cell-based assays. The results show that diphyllin alters cellular susceptibility to influenza viruses through the inhibition of endosomal acidification, thus interfering with downstream virus replication, including that of known drug-resistant strains. In addition, combinatorial treatment of the host-targeting diphyllin with pathogen-targeting therapeutics (oseltamivir and amantadine) demonstrates enhanced antiviral effects and cell protection in vitro.
Copyright ? 2013. Published by Elsevier B.V.
PMID:
23820269
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23820269
Inhibitory and combinatorial effect of diphyllin, a v-ATPase blocker, on influenza viruses.
Chen HW, Cheng JX, Liu MT, King K, Peng JY, Zhang XQ, Wang CH, Shresta S, Schooley RT, Liu YT.
Source
Division of Infectious Disease, School of Medicine, University of California San Diego. 9500 Gilman Drive, La Jolla, CA 92093, United Sates of America; Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology. 9420 Athena Circle, La Jolla, CA 92037, United States of America; School of Veterinary Medicine, National Taiwan University. No. 1, Sec. 4 Roosevelt Road, Taipei 10617, Taiwan.
Abstract
An influenza pandemic poses a serious threat to humans and animals. Conventional treatments against influenza include two classes of pathogen-targeting antivirals: M2 ion channel blockers (such as amantadine) and neuraminidase inhibitors (such as oseltamivir). Examination of the mechanism of influenza viral infection has shown that endosomal acidification plays a major role in facilitating the fusion between viral and endosomal membranes. This pathway has led to investigations on vacuolar ATPase (v-ATPase) activity, whose role as a regulating factor on influenza virus replication has been verified in extensive genome-wide screenings. Blocking v-ATPase activity thus presents the opportunity to interfere with influenza viral infection by preventing the pH-dependent membrane fusion between endosomes and virions. This study aims to apply diphyllin, a natural compound shown to be as a novel v-ATPase inhibitor, as a potential antiviral for various influenza virus strains using cell-based assays. The results show that diphyllin alters cellular susceptibility to influenza viruses through the inhibition of endosomal acidification, thus interfering with downstream virus replication, including that of known drug-resistant strains. In addition, combinatorial treatment of the host-targeting diphyllin with pathogen-targeting therapeutics (oseltamivir and amantadine) demonstrates enhanced antiviral effects and cell protection in vitro.
Copyright ? 2013. Published by Elsevier B.V.
PMID:
23820269
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23820269