title: Discovery of drugs that possess activity against feline leukemia virus.
abstract: Feline leukemia virus (FeLV) is a gammaretrovirus that is a significant cause of neoplastic-related disorders affecting cats worldwide. Treatment options for FeLV are limited, associated with serious side effects, and can be cost-prohibitive. The development of drugs used to treat a related retrovirus, human immunodeficiency virus type 1 (HIV-1), has been rapid, leading to the approval of five drug classes. Although structural differences affect the susceptibility of gammaretroviruses to anti-HIV drugs, the similarities in mechanism of replication suggest that some anti-HIV-1 drugs may also inhibit FeLV. This study demonstrates the anti-FeLV activity of four drugs approved by the US FDA (Food and Drug Administration) at non-toxic concentrations. Of these, tenofovir and raltegravir are anti-HIV-1 drugs, while decitabine and gemcitabine are approved to treat myelodysplastic syndromes and pancreatic cancer, respectively, but also have anti-HIV-1 activity in cell culture. Our results indicate that these drugs may be useful for FeLV treatment and should be investigated for mechanism of action and suitability for veterinary use.
authors.affiliation: Comparative Molecular Biosciences Graduate Program, College of Veterinary Medicine, University of Minnesota, MN 55455, USA.|Institute for Molecular Virology, Academic Health Center, University of Minnesota, MN 55455 USA.
authors.forename: Willie M
authors.initials: WM
authors.lastname: Greggs
authors.affiliation: Department of Diagnostic and Biological Sciences, School of Dentistry, University of Minnesota, MN 55455, USA.|Institute for Molecular Virology, Academic Health Center, University of Minnesota, MN 55455 USA.
authors.forename: Christine L
authors.initials: CL
authors.lastname: Clouser
authors.affiliation: Center for Drug Design, Academic Health Center, University of Minnesota, MN 55455, USA.|Institute for Molecular Virology, Academic Health Center, University of Minnesota, MN 55455 USA.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Patterson
authors.affiliation: Department of Microbiology, Medical School, University of Minnesota, MN 55455, USA.|Comparative Molecular Biosciences Graduate Program, College of Veterinary Medicine, University of Minnesota, MN 55455, USA.|Center for Drug Design, Academic Health Center, University of Minnesota, MN 55455, USA.|Institute for Molecular Virology, Academic Health Center, University of Minnesota, MN 55455 USA.|Department of Diagnostic and Biological Sciences, School of Dentistry, University of Minnesota, MN 55455, USA.
authors.forename: Louis M
authors.initials: LM
authors.lastname: Mansky
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D001374:Azacitidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D002371:Cat Diseases / Q000188:drug therapy / Q000821:virology*; D002415:Cats; D000077209:Decitabine; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005256:Leukemia Virus, Feline / Q000187:drug effects*; D016582:Leukemia, Feline / Q000188:drug therapy; D063065:Organophosphonates / Q000627:therapeutic use; D011760:Pyrrolidinones / Q000627:therapeutic use; D000068898:Raltegravir Potassium; D012192:Retroviridae Infections / Q000188:drug therapy / Q000662:veterinary*; D000068698:Tenofovir; D014412:Tumor Virus Infections / Q000188:drug therapy / Q000662:veterinary*; D000093542:Gemcitabine
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; D011760:Pyrrolidinones; D003841:Deoxycytidine; D000068898:Raltegravir Potassium; D000077209:Decitabine; D000068698:Tenofovir; D000225:Adenine; D001374:Azacitidine; D000093542:Gemcitabine