Research Statement

My research focuses on the biology, evolution and pathogenesis of nidoviruses (corona-, arteri-, bafini- and roniviruses) and the molecular mechanisms involved in viral genome replication and expression. The major goal of these studies is to obtain a detailed understanding of the proteins/enzymes and mechanisms involved in viral RNA replication and pathogenesis and then use this information to develop new and better strategies to combat infections caused by these important human and animal pathogens.

Publications

Chapter(s)
Title	Book Title	Year
Expression and functions of SARS coronavirus replicative proteins	Molecular Biology of the SARS-Coronavirus	2010
SARS coronavirus replicative enzymes: structures and mechanisms	Molecular Biology of the SARS-Coronavirus	2010
Coronavirus replicative proteins	Nidoviruses	2008
Nidovirales	Encyclopedia of Virology	2008
The coronavirus replicase gene: special enzymes for special viruses	Coronaviruses - Molecular and Cellular Biology	2007
The coronavirus replicase: insights into a sophisticated enzyme machinery	The Nidoviruses: Toward Control of SARS and other Nidovirus Diseases	2006
Coronaviruses, toroviruses, and arteriviruses	Topley & Wilson's Microbiology and Microbial Infections	2005
Journal(s)
Title	Journal Name	Year
Characterization of bafinivirus main protease autoprocessing activities	Journal of Virology Vol 85 (1348-1359)  DOI	2011
Ribose 2'-O-methylation provides a molecular signature for the distinction of self and non-self mRNA dependent on the RNA sensor Mda5.	Nature Immunology Vol 12(2) (137-143)  DOI	2011
Nidovirus ribonucleases: Structures and functions in viral replication.	RNA biology Vol 8(2) (295-304)	2011
Biochemical characterization of arterivirus nonstructural protein 11 reveals the nidovirus-wide conservation of a replicative endoribonuclease	Journal of Virology Vol 83 (5671-5682)  DOI	2009
Human coronavirus 229E papain-like proteases have overlapping specificities but distinct functions in viral replication.	Journal of Virology Vol 81 (3922-3932)  DOI	2007
Discovery of an RNA virus 3'->5' exoribonuclease that is critically involved in coronavirus RNA synthesis	Proceedings of the National Academy of Sciences Vol 103(13) (5108-5113)  DOI	2006
Characterization of White bream virus reveals a novel genetic cluster of nidoviruses.	Journal of Virology Vol 80 (11598-11609)  DOI	2006
Structural and functional basis for ADP-ribose and poly(ADP-ribose) binding by viral macro domains.	Journal of Virology Vol 80 (8493-8502)  DOI	2006
Nidovirales: evolving the largest RNA virus genome.	Virus Research Vol 117 (17-37)  DOI	2006
Identification of protease and ADP-ribose 1''-monophosphatase activities associated with transmissible gastroenteritis virus non-structural protein 3.	Journal of General Virology Vol 87 (651-656)  DOI	2006
Crystal structure and mechanistic determinants of SARS coronavirus nonstructural protein 15 define an endoribonuclease family.	Proceedings of the National Academy of Sciences of the United States of America Vol 103(32) (11892-11897)  DOI	2006
A new lead for nonpeptidic active-site-directed inhibitors of the severe acute respiratory syndrome coronavirus main protease discovered by a combination of screening and docking methods.	Journal of Medicinal Chemistry Vol 48 (6832-6842)  DOI	2005
Screening of electrophilic compounds yields an aziridinyl peptide as new active-site directed SARS-CoV main protease inhibitor.	Bioorganic & Medicinal Chemistry Letters Vol 15 (5365-5369)  DOI	2005
ADP-Ribose-1"-Monophosphatase: a Conserved Coronavirus Enzyme That Is Dispensable for Viral Replication in Tissue Culture	Journal of Virology Vol 79 (12721-12731)  DOI	2005
A complex zinc finger controls the enzymatic activities of nidovirus helicases.	Journal of Virology Vol 79 (696-704)  DOI	2005
The coronavirus replicase.	Current Topics in Microbiology and Immunology Vol 287 (57-94)	2005
Design of wide-spectrum inhibitors targeting coronavirus main proteases.	PLoS Biology Vol 3 (e324/1-e324/11)  DOI	2005
Major genetic marker of nidoviruses encodes a replicative endoribonuclease	Proceedings of the National Academy of Sciences Vol 101(34) (12694-12699)  DOI	2004
Multiple Enzymatic Activities Associated with Severe Acute Respiratory Syndrome Coronavirus Helicase	Journal of Virology Vol 78(11) (5619-5632)  DOI	2004
Human coronavirus 229E nonstructural protein 13: characterization of duplex-unwinding, nucleoside triphosphatase, and RNA 5'-triphosphatase activities.	Journal of Virology Vol 78 (7833-7838)  DOI	2004
Molecular biology of severe acute respiratory syndrome coronavirus.	Current Opinion in Microbiology Vol 7 (412-419)  DOI	2004
Rapid identification of coronavirus replicase inhibitors using a selectable replicon RNA.	Journal of General Virology Vol 85 (1717-1725)  DOI	2004
Coronavirus Main Proteinase (3CLpro) Structure: Basis for Design of Anti-SARS Drugs	Science Vol 300(5626) (1763-1767)  DOI	2003
Unique and conserved features of genome and proteome of SARS-coronavirus, an early split-off from the coronavirus group 2 lineage.	Journal of Molecular Biology Vol 331 (991-1004)  DOI	2003
Mechanisms and enzymes involved in SARS coronavirus genome expression.	Journal of General Virology Vol 84 (2305-2315)  DOI	2003
The 3C-like proteinase of an invertebrate nidovirus links coronavirus and potyvirus homologs.	Journal of Virology Vol 77 (1415-1426)  DOI	2003
Structure of coronavirus main proteinase reveals combination of a chymotrypsin fold with an extra alpha-helical domain.	The EMBO Journal Vol 21 (3213-3224)  DOI	2002
Conservation of substrate specificities among coronavirus main proteases.	Journal of General Virology Vol 83 (595-599)	2002
The autocatalytic release of a putative RNA virus transcription factor from its polyprotein precursor involves two paralogous papain-like proteases that cleave the same peptide bond.	Journal of Biological Chemistry Vol 276 (33220-33232)  DOI	2001
The human coronavirus 229E superfamily 1 helicase has RNA and DNA duplex-unwinding activities with 5'-to-3' polarity.	RNA Vol 6 (1056-1068)	2000
Biochemical characterization of the equine arteritis virus helicase suggests a close functional relationship between arterivirus and coronavirus helicases.	Journal of Virology Vol 74 (9586-9593)	2000
Virus-encoded proteinases and proteolytic processing in the Nidovirales.	Journal of General Virology Vol 81 (853-879)	2000