Cinanserin Is an Inhibitor of the 3C-Like Proteinase of Severe Acute Respiratory Syndrome Coronavirus and Strongly Reduces Virus Replication In Vitro

  title={Cinanserin Is an Inhibitor of the 3C-Like Proteinase of Severe Acute Respiratory Syndrome Coronavirus and Strongly Reduces Virus Replication In Vitro},
  author={Li-li Chen and Chunshan Gui and Xiaomin Luo and Qingang Yang and Stephan G{\"u}nther and Elke Scandella and Christian Drosten and Dong-lu Bai and X C He and Burkhard Ludewig and Jing Chen and Haibin Luo and Yiming Yang and Yifu Yang and Jianping Zou and Volker Thiel and Kaixian Chen and Jianhua Shen and Xu Shen and Hualiang Jiang},
  journal={Journal of Virology},
  pages={7095 - 7103}
ABSTRACT The 3C-like proteinase (3CLpro) of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is one of the most promising targets for anti-SARS-CoV drugs due to its crucial role in the viral life cycle. In this study, a database containing structural information of more than 8,000 existing drugs was virtually screened by a docking approach to identify potential binding molecules of SARS-CoV 3CLpro. As a target for screening, both a homology model and the crystallographic… 
Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors
A programme of structure-assisted drug design and high-throughput screening identifies six compounds that inhibit the main protease of SARS-CoV-2, demonstrating the ability of this strategy to isolate drug leads with clinical potential.
Several coumarin derivatives and their Pd(ii) complexes as potential inhibitors of the main protease of SARS-CoV-2, an in silico approach
Results showed that the molecules bearing structural similarity to the approved drugs and their complexes have the potential to inhibit the functional activity of SARS-CoV-2 protease and further experimental studies should be undertaken.
Design and Evaluation of Anti-SARS-Coronavirus Agents Based on Molecular Interactions with the Viral Protease
A series of studies on SARS-CoV are reviewed, focusing on the development of inhibitors for the SARS -CoV 3CLpro based on molecular interactions with the 3CL protease, which is thought to be an ideal therapeutic agent against SARS, MERS, or COVID-19.
Characterization and Inhibition of the Main Protease of Severe Acute Respiratory Syndrome Coronavirus
Current developments in anti‐SARS agents targeting 3CLpro and the application of the mutant protease as a tag‐cleavage endopeptidase are summarized.
Discovery of a novel family of SARS-CoV protease inhibitors by virtual screening and 3D-QSAR studies.
A search for analogues with common substructure in the Maybridge, ChemBridge, and SPECS_SC databases led to the identification of another 25 compounds that exhibited inhibition against SARS-CoV 3CL(pro) (IC(50) = 3-1,000 microM).
Substrate specificity profiling and identification of a new class of inhibitor for the major protease of the SARS coronavirus.
A complete description of the tetrapeptide substrate specificity of 3Clpro is reported using fully degenerate peptide libraries consisting of all 160,000 possible naturally occurring tetrapptides to provide the foundation for a rational small-molecule inhibitor design effort based upon the inhibitor scaffold identified, the crystal structure of the complex, and a more complete understanding of P1-P4 substrate specificity.


Coronavirus Main Proteinase (3CLpro) Structure: Basis for Design of Anti-SARS Drugs
Molecular modeling suggests that available rhinovirus 3Cpro inhibitors may be modified to make them useful for treating SARS, and a homology model for SARS coronavirus (SARS-CoV) Mpro is constructed.
Exploring the binding mechanism of the main proteinase in SARS-associated coronavirus and its implication to anti-SARS drug design
The crystal structures of severe acute respiratory syndrome virus main protease and its complex with an inhibitor
  • Haitao Yang, Maojun Yang, Z. Rao
  • Chemistry, Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 2003
This series of crystal structures, which is the first, to the authors' knowledge, of any protein from the SARS virus, reveal substantial pH-dependent conformational changes, and an unexpected mode of inhibitor binding, providing a structural basis for rational drug design.
Identifying inhibitors of the SARS coronavirus proteinase
Small molecules targeting severe acute respiratory syndrome human coronavirus.
A cell-based assay was developed to screen existing drugs, natural products, and synthetic compounds to identify effective anti-SARS agents, and of particular interest are the two anti-HIV agents, one as an entry blocker and the other as a 3CL protease inhibitor.
Molecular cloning, expression, purification, and mass spectrometric characterization of 3C-like protease of SARS coronavirus
Application of real-time PCR for testing antiviral compounds against Lassa virus, SARS coronavirus and Ebola virus in vitro
Identification of Severe Acute Respiratory Syndrome Coronavirus Replicase Products and Characterization of Papain-Like Protease Activity
This work identifies SARS coronavirus amino-terminal replicase products nsp1, nsp2, and nsp3 and describes trans-cleavage assays that characterize the protease activity required to generate these products and revealed that PLpro can cleave in trans at the three predicted cleavage sites and that it requires membrane association to process the nSP3/4 cleavage site.
Characterization of SARS main protease and inhibitor assay using a fluorogenic substrate
Mechanisms and enzymes involved in SARS coronavirus genome expression.
The availability of recombinant forms of key replicative enzymes of SARS coronavirus should pave the way for high-throughput screening approaches to identify candidate inhibitors in compound libraries.