Coronavirus main proteinase (3CLpro) structure: basis for design of anti-SARS drugs
- PMID: 12746549
- DOI: 10.1126/science.1085658
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.
Similar articles
-
The SARS-coronavirus papain-like protease: structure, function and inhibition by designed antiviral compounds.Antiviral Res. 2015 Mar;115:21-38. doi: 10.1016/j.antiviral.2014.12.015. Epub 2014 Dec 29. Antiviral Res. 2015. PMID: 25554382 Free PMC article. Review.
-
The newly emerged SARS-like coronavirus HCoV-EMC also has an "Achilles' heel": current effective inhibitor targeting a 3C-like protease.Protein Cell. 2013 Apr;4(4):248-50. doi: 10.1007/s13238-013-2841-3. Protein Cell. 2013. PMID: 23549610 Free PMC article. No abstract available.
-
Drug design targeting the main protease, the Achilles' heel of coronaviruses.Curr Pharm Des. 2006;12(35):4573-90. doi: 10.2174/138161206779010369. Curr Pharm Des. 2006. PMID: 17168763 Review.
-
Design of wide-spectrum inhibitors targeting coronavirus main proteases.PLoS Biol. 2005 Oct;3(10):e324. doi: 10.1371/journal.pbio.0030324. Epub 2005 Sep 6. PLoS Biol. 2005. PMID: 16128623 Free PMC article.
-
A 3D model of SARS_CoV 3CL proteinase and its inhibitors design by virtual screening.Acta Pharmacol Sin. 2003 Jun;24(6):497-504. Acta Pharmacol Sin. 2003. PMID: 12791174
Cited by
-
Role of marine natural products in the development of antiviral agents against SARS-CoV-2: potential and prospects.Mar Life Sci Technol. 2024 Feb 21;6(2):280-297. doi: 10.1007/s42995-023-00215-9. eCollection 2024 May. Mar Life Sci Technol. 2024. PMID: 38827130 Review.
-
Unveiling the Multifaceted Capabilities of Endophytic Aspergillus flavus Isolated from Annona squamosa Fruit Peels against Staphylococcus Isolates and HCoV 229E-In Vitro and In Silico Investigations.Pharmaceuticals (Basel). 2024 May 19;17(5):656. doi: 10.3390/ph17050656. Pharmaceuticals (Basel). 2024. PMID: 38794226 Free PMC article.
-
Phytoconstituents of Artemisia Annua as potential inhibitors of SARS CoV2 main protease: an in silico study.BMC Infect Dis. 2024 May 15;24(1):495. doi: 10.1186/s12879-024-09387-w. BMC Infect Dis. 2024. PMID: 38750422 Free PMC article.
-
Aminoguanidine-based bioactive proligand as AIEE probe for anticancer and anticovid studies.RSC Adv. 2024 Apr 25;14(19):13654-13668. doi: 10.1039/d4ra00554f. eCollection 2024 Apr 22. RSC Adv. 2024. PMID: 38665490 Free PMC article.
-
Quinazolines and thiazolidine-2,4-dions as SARS-CoV-2 inhibitors: repurposing, in silico molecular docking and dynamics simulation.RSC Adv. 2024 Apr 23;14(19):13237-13250. doi: 10.1039/d4ra02029d. eCollection 2024 Apr 22. RSC Adv. 2024. PMID: 38655479 Free PMC article.
Publication types
MeSH terms
Substances
Associated data
- Actions
- Actions
- Actions
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases
Miscellaneous