title: A Novel Iminosugar UV-12 with Activity against the Diverse Viruses Influenza and Dengue (Novel Iminosugar Antiviral for Influenza and Dengue).
abstract: Iminosugars are capable of targeting the life cycles of multiple viruses by blocking host endoplasmic reticulum α-glucosidase enzymes that are required for competent replication of a variety of enveloped, glycosylated viruses. Iminosugars as a class are approved for use in humans with diseases such as diabetes and Gaucher's disease, providing evidence for safety of this class of compounds. The in vitro antiviral activity of iminosugars has been described in several publications with a subset of these demonstrating in vivo activity against flaviviruses, herpesviruses, retroviruses and filoviruses. Although there is compelling non-clinical in vivo evidence of antiviral efficacy, the efficacy of iminosugars as antivirals has yet to be demonstrated in humans. In the current study, we report a novel iminosugar, UV-12, which has efficacy against dengue and influenza in mouse models. UV-12 exhibits drug-like properties including oral bioavailability and good safety profile in mice and guinea pigs. UV-12 is an example of an iminosugar with activity against multiple virus families that should be investigated in further safety and efficacy studies and demonstrates potential value of this drug class as antiviral therapeutics.
authors.affiliation: Unither Virology LLC, Silver Spring, MD 20910, USA. kwarfield@unithervirology.com.
authors.forename: Kelly L
authors.initials: KL
authors.lastname: Warfield
authors.affiliation: La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA. eplummer@liai.org.
authors.forename: Emily
authors.initials: E
authors.lastname: Plummer
authors.affiliation: Oxford Glycobiology Institute, Oxford OX1 3QU, UK,. dominic.alonzi@bioch.ox.ac.uk.
authors.forename: Dominic S
authors.initials: DS
authors.lastname: Alonzi
authors.affiliation: Gary Wolfe Toxicology, Herndon, VA 20170, USA. gary@gwtox.com.
authors.forename: Gary W
authors.initials: GW
authors.lastname: Wolfe
authors.affiliation: Unither Virology LLC, Silver Spring, MD 20910, USA. asampath@unithervirology.com.
authors.forename: Aruna
authors.initials: A
authors.lastname: Sampath
authors.affiliation: Tam Nguyen LLC, Gaithersburg, MD 20879, USA. tam.3.nguyen@gmail.com.
authors.forename: Tam
authors.initials: T
authors.lastname: Nguyen
authors.affiliation: Oxford Glycobiology Institute, Oxford OX1 3QU, UK,. terry.butters@btinternet.com.
authors.forename: Terry D
authors.initials: TD
authors.lastname: Butters
authors.affiliation: Integrated Biotherapeutics, Gaithersburg, MD 20878, USA. sven@integratedbiotherapeutics.com.
authors.forename: Sven G
authors.initials: SG
authors.lastname: Enterlein
authors.affiliation: Integrated Biotherapeutics, Gaithersburg, MD 20878, USA. eric@integratedbiotherapeutics.com.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Stavale
authors.affiliation: La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA. sujan@lji.org.
authors.forename: Sujan
authors.initials: S
authors.lastname: Shresta
authors.affiliation: Unither Virology LLC, Silver Spring, MD 20910, USA. urban_ramstedt@yahoo.com.
authors.forename: Urban
authors.initials: U
authors.lastname: Ramstedt
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003715:Dengue / Q000188:drug therapy*; D003716:Dengue Virus / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D006168:Guinea Pigs; D050111:Imino Sugars / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D009975:Orthomyxoviridae / Q000187:drug effects; D009976:Orthomyxoviridae Infections / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D050111:Imino Sugars
keywords: Flaviviridae; Orthomyxoviridae; flavivirus; glucosidase; glycosylation; mouse; orthomyxovirus