title: Processing of viral glycoproteins by the subtilisin-like endoprotease furin and its inhibition by specific peptidylchloroalkylketones.
abstract: The spike glycoproteins of many enveloped viruses are proteolytically cleaved at the carboxytermini of sequences containing the basic motif R-X-K/R-R. Cleavage is often necessary for the fusion capacity of the glycoproteins and, thus, for virus infectivity. Among these viruses are pathogenic avian influenza viruses, human parainfluenza virus, human cytomegalovirus, and human immunodeficiency virus; it has been demonstrated that these viruses can be activated by furin. Indigenous furin has been identified in T-lymphocytes, which are host cells for HIV. Furin has been localized in the TGN and on the surface of cells after vectorial expression. Peptidylchloroalkylketones have been designed that inhibit with high specificity cleavage and fusion activity of viral glycoproteins, as well as virus replication.
authors: Institut für Virologie, Philipps-Universität Marburg, Germany.
authors: W
authors: W
authors: Garten
authors: S
authors: S
authors: Hallenberger
authors: D
authors: D
authors: Ortmann
authors: W
authors: W
authors: Schäfer
authors: M
authors: M
authors: Vey
authors: H
authors: H
authors: Angliker
authors: E
authors: E
authors: Shaw
authors: H D
authors: HD
authors: Klenk
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D016384:Consensus Sequence; D045683:Furin; D006678:HIV / Q000378:metabolism; D008969:Molecular Sequence Data; D011480:Protease Inhibitors / Q000494:pharmacology*; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D013379:Substrate Specificity; D013381:Subtilisins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013601:T-Lymphocytes / Q000201:enzymology; D014764:Viral Proteins / Q000096:biosynthesis* / Q000737:chemistry; D014780:Viruses / Q000378:metabolism
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D011480:Protease Inhibitors; D014764:Viral Proteins; D013381:Subtilisins; D045683:Furin