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Human coronavirus OC43 3CL protease and the potential of ML188 as a broad-spectrum lead compound: Homology modelling and molecular dynamic studies

Overview of attention for article published in BMC Structural Biology, April 2015
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Title
Human coronavirus OC43 3CL protease and the potential of ML188 as a broad-spectrum lead compound: Homology modelling and molecular dynamic studies
Published in
BMC Structural Biology, April 2015
DOI 10.1186/s12900-015-0035-3
Pubmed ID
Authors

Michael Berry, Burtram Fielding, Junaid Gamieldien

Abstract

The coronavirus 3 chymotrypsin-like protease (3CL(pro)) is a validated target in the design of potential anticoronavirus inhibitors. The high degree of homology within the protease's active site and substrate conservation supports the identification of broad spectrum lead compounds. A previous study identified the compound ML188, also termed 16R, as an inhibitor of the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) 3CL(pro). This study will detail the generation of a homology model of the 3CL(pro) of the human coronavirus OC43 and determine the potential of 16R to form a broad-spectrum lead compound. MODELLER was used to generate a suitable three-dimensional model of the OC43 3CL(pro) and the Prime module of Schrӧdinger predicted the binding conformation and free energy of binding of 16R within the 3CL(pro) active site. Molecular dynamics further confirmed ligand stability and hydrogen bonding networks. A high quality homology model of the OC43 3CL(pro) was successfully generated in an active conformation. Further studies reproduced the binding pose of 16R within the active site of the generated model, where its free energy of binding was shown to equal that of the 3CL(pro) of SARS-CoV, a receptor it is experimentally proven to inhibit. The stability of the ligand was subsequently confirmed by molecular dynamics. The lead compound 16R may represent a broad-spectrum inhibitor of the 3CL(pro) of OC43 and potentially other coronaviruses. This study provides an atomistic structure of the 3CL(pro) of OC43 and supports further experimental validation of the inhibitory effects of 16R. These findings further confirm that the 3CL(pro) of coronaviruses can be inhibited by broad spectrum lead compounds.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 34 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Canada 1 3%
Unknown 33 97%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 7 21%
Student > Master 7 21%
Researcher 6 18%
Other 3 9%
Professor > Associate Professor 2 6%
Other 7 21%
Unknown 2 6%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 7 21%
Agricultural and Biological Sciences 5 15%
Veterinary Science and Veterinary Medicine 4 12%
Immunology and Microbiology 3 9%
Pharmacology, Toxicology and Pharmaceutical Science 3 9%
Other 9 26%
Unknown 3 9%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 21 January 2016.
All research outputs
#7,173,118
of 8,295,152 outputs
Outputs from BMC Structural Biology
#118
of 144 outputs
Outputs of similar age
#277,953
of 331,912 outputs
Outputs of similar age from BMC Structural Biology
#5
of 6 outputs
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