Coronavirus main proteinase (3CLpro) Structure: Basis for design of anti-SARS drugs

Kanchan Anand; John Ziebuhr; Parvesh Wadhwani; Jeroen R. Mesters; Rolf Hilgenfeld

doi:10.1126/science.1085658

Coronavirus main proteinase (3CL^pro) Structure: Basis for design of anti-SARS drugs

Kanchan Anand, John Ziebuhr, Parvesh Wadhwani, Jeroen R. Mesters, Rolf Hilgenfeld^*

^*Korrespondierende/r Autor/-in für diese Arbeit

Institut für Biochemie

1579 Zitate (Scopus)

Abstract

A novel coronavirus has been identified as the causative agent of severe acute respiratory syndrome (SARS). The viral main proteinase (M^pro, also called 3CL^pro), which controls the activities of the coronavirus replication complex, is an attractive target for therapy. We determined crystal structures for human coronavirus (strain 229E) M^pro and for an inhibitor complex of porcine coronavirus [transmissible gastroenteritis virus (TGEV)] M^pro and we constructed a homology model for SARS coronavirus (SARS-CoV) M^pro. The structures reveal a remarkable degree of conservation of the substrate-binding sites, which is further supported by recombinant SARS-CoV M^pro-mediated cleavage of a TGEV M^pro substrate. Molecular modeling suggests that available rhinovirus 3C^pro inhibitors may be modified to make them useful for treating SARS.

Originalsprache	Englisch
Zeitschrift	Science
Jahrgang	300
Ausgabenummer	5626
Seiten (von - bis)	1763-1767
Seitenumfang	5
ISSN	0036-8075
DOIs	https://doi.org/10.1126/science.1085658
Publikationsstatus	Veröffentlicht - 13.06.2003

Strategische Forschungsbereiche und Zentren

Forschungsschwerpunkt: Infektion und Entzündung - Zentrum für Infektions- und Entzündungsforschung Lübeck (ZIEL)

Coronavirus-Bezug

Forschung zu SARS-CoV-2 / COVID-19

UN SDGs

Dieser Output leistet einen Beitrag zu folgendem(n) Ziel(en) für nachhaltige Entwicklung

Dokumente

10.1126/science.1085658

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Coronavirus main proteinase (3CLpro) Structure: Basis for design of anti-SARS drugs