title: An Overview of Severe Acute Respiratory Syndrome-Coronavirus (SARS-CoV) 3CL Protease Inhibitors: Peptidomimetics and Small Molecule Chemotherapy.
abstract: Severe acute respiratory syndrome (SARS) is caused by a newly emerged coronavirus that infected more than 8000 individuals and resulted in more than 800 (10-15%) fatalities in 2003. The causative agent of SARS has been identified as a novel human coronavirus (SARS-CoV), and its viral protease, SARS-CoV 3CL(pro), has been shown to be essential for replication and has hence been recognized as a potent drug target for SARS infection. Currently, there is no effective treatment for this epidemic despite the intensive research that has been undertaken since 2003 (over 3500 publications). This perspective focuses on the status of various efficacious anti-SARS-CoV 3CL(pro) chemotherapies discovered during the last 12 years (2003-2015) from all sources, including laboratory synthetic methods, natural products, and virtual screening. We describe here mainly peptidomimetic and small molecule inhibitors of SARS-CoV 3CL(pro). Attempts have been made to provide a complete description of the structural features and binding modes of these inhibitors under many conditions.
authors.affiliation: Pharmaceutical Institute, Pharmaceutical Chemistry I, University of Bonn , An der Immenburg 4, D-53121 Bonn, Germany.
authors.forename: Thanigaimalai
authors.initials: T
authors.lastname: Pillaiyar
authors.affiliation: College of Pharmacy and Institute of Drug Research and Development, Chungnam National University , Daejeon 34134, South Korea.
authors.forename: Manoj
authors.initials: M
authors.lastname: Manickam
authors.affiliation: Pharmaceutical Institute, Pharmaceutical Chemistry I, University of Bonn , An der Immenburg 4, D-53121 Bonn, Germany.
authors.forename: Vigneshwaran
authors.initials: V
authors.lastname: Namasivayam
authors.affiliation: Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences , Tokyo 192-0392, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hayashi
authors.affiliation: College of Pharmacy and Institute of Drug Research and Development, Chungnam National University , Daejeon 34134, South Korea.
authors.forename: Sang-Hun
authors.initials: SH
authors.lastname: Jung
mesh_terms: D000818:Animals; D000086782:Coronavirus 3C Proteases; D003546:Cysteine Endopeptidases / Q000378:metabolism; D006801:Humans; D008968:Molecular Conformation; D057786:Peptidomimetics / Q000737:chemistry / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014764:Viral Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D057786:Peptidomimetics; D011480:Protease Inhibitors; D054852:Small Molecule Libraries; D014764:Viral Proteins; D003546:Cysteine Endopeptidases; D000086782:Coronavirus 3C Proteases