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^*

^*Corresponding author for this work

Institute of Biochemistry

514 Citations (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.

Original language	English
Journal	Science
Volume	300
Issue number	5626
Pages (from-to)	1763-1767
Number of pages	5
ISSN	0036-8075
DOIs	https://doi.org/10.1126/science.1085658
Publication status	Published - 13.06.2003

Research Areas and Centers

Academic Focus: Center for Infection and Inflammation Research (ZIEL)

Coronavirus related work

Research on SARS-CoV-2 / COVID-19

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1126/science.1085658

Cite this

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

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

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AU - Hilgenfeld, Rolf

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