Coronavirus Main Proteinase (3CL) Structure: Basis for Design of Anti-SARS Drugs

نویسندگان

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

(1999). 32. C. L. Colby, J. R. Duhamel, M. E. Goldberg, Cereb. Cortex 5, 470 (1995). 33. K. Nakamura, C. L. Colby, Proc. Natl. Acad. Sci. U.S.A. 99, 4026 (2002). 34. S. Ben Hamed, J. R. Duhamel, Exp. Brain Res. 142, 512 (1998). 35. B. Gaymard, C. J. Ploner, S. Rivaud, A. I. Vermersch, C. Pierrot-Deseilligny, Exp. Brain Res. 123, 159 (1998). 36. D. C. Somers, S. B. Nelson, M. Sur, J. Neurosci. 15, 5448 (1995). 37. V. Dragoi, J. Sharma, E. K. Miller, M. Sur, Nature Neurosci. 5, 883 (2002). 38. We thank P. Sinha for insightful discussions and comments and J. Schummers, J. Mariño, B. Scott, and D. Lyon for careful reading of the manuscript and suggestions. Supported by a fellowship from the McDonnell-Pew Foundation (V.D.) and grants from NIH (M.S.). Supporting Online Material www.sciencemag.org/cgi/content/full/300/5626/1758/ DC1 Materials and Methods SOM Text Fig. S1 References

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Exploring the binding mechanism of the main proteinase in SARS-associated coronavirus and its implication to anti-SARS drug design.

The main proteinase of SARS-associated coronavirus (SARS-CoV) plays an important role in viral transcription and replication, and is an attractive target for anti-SARS drug development. The important thing is to understand its binding mechanism with possible ligands. In this study, we investigated possible noncanonical interactions, potential inhibitors, and binding pockets in the main proteina...

متن کامل

Severe Acute Respiratory Syndrome Coronavirus 3C-like Proteinase N Terminus Is Indispensable for Proteolytic Activity but Not for Enzyme Dimerization BIOCHEMICAL AND THERMODYNAMIC INVESTIGATION IN CONJUNCTION WITH MOLECULAR DYNAMICS SIMULATIONS*□S

Severe acute respiratory syndrome (SARS) coronavirus is a novel human coronavirus and is responsible for SARS infection. SARS coronavirus 3C-like proteinase (SARS 3CL) plays key roles in viral replication and transcription and is an attractive target for anti-SARS drug discovery. In this report, we quantitatively characterized the dimerization features of the full-length and N-terminal residues...

متن کامل

Design and synthesis of cinanserin analogs as severe acute respiratory syndrome coronavirus 3CL protease inhibitors.

The severe acute respiratory syndrome (SARS) coronavirus 3CL protease is an attractive target for the development of anti-SARS drugs. In this paper, cinanserin (1) analogs were synthesized and tested for the inhibitory activities against SARS-coronavirus (CoV) 3CL protease by fluorescence resonance energy transfer (FRET) assay. Four analogs show significant activities, especially compound 26 wi...

متن کامل

Old drugs as lead compounds for a new disease? Binding analysis of SARS coronavirus main proteinase with HIV, psychotic and parasite drugs.

The SARS-associated coronavirus (SARS-CoV) main proteinase is a key enzyme in viral polyprotein processing. To allow structure-based design of drugs directed at SARS-CoV main proteinase, we predicted its binding pockets and affinities with existing HIV, psychotic and parasite drugs (lopinavir, ritonavir, niclosamide and promazine), which show signs of inhibiting the replication of SARS-CoV. Our...

متن کامل

Coronavirus main proteinase (3CLpro) structure: basis for design of anti-SARS drugs.

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 [t...

متن کامل

Characterization and Inhibition of the Main Protease of Severe Acute Respiratory Syndrome Coronavirus

The main protease of SARS-associated coronavirus (SARS-CoV), also called 3C-like protease (3CL), is vital for the viral replication. It cleaves the replicase polyproteins at 11 sites and is a promising drug target. Several groups of inhibitors have been identified through high-throughput screening and rational drug design. In addition to the pharmaceutical applications, a mutant 3CL (T25G) with...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره   شماره 

صفحات  -

تاریخ انتشار 2003