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Bioorg Med Chem. 2016 Jul 1;24(13):3035-3042. doi: 10.1016/j.bmc.2016.05.013. Epub 2016 May 12.

Identification, synthesis and evaluation of SARS-CoV and MERS-CoV 3C-like protease inhibitors.

Author information

1
Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan.
2
Institute of Biochemical Sciences, National Taiwan University, Taipei 106, Taiwan.
3
Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan; Institute of Biochemical Sciences, National Taiwan University, Taipei 106, Taiwan. Electronic address: phliang@gate.sinica.edu.tw.

Abstract

Severe acute respiratory syndrome (SARS) led to a life-threatening form of atypical pneumonia in late 2002. Following that, Middle East Respiratory Syndrome (MERS-CoV) has recently emerged, killing about 36% of patients infected globally, mainly in Saudi Arabia and South Korea. Based on a scaffold we reported for inhibiting neuraminidase (NA), we synthesized the analogues and identified compounds with low micromolar inhibitory activity against 3CL(pro) of SARS-CoV and MERS-CoV. Docking studies show that a carboxylate present at either R(1) or R(4) destabilizes the oxyanion hole in the 3CL(pro). Interestingly, 3f, 3g and 3m could inhibit both NA and 3CL(pro) and serve as a starting point to develop broad-spectrum antiviral agents.

KEYWORDS:

3CL(pro); Coronavirus; MERS-CoV; Pyrazolone; SARS-Cov

PMID:
27240464
DOI:
10.1016/j.bmc.2016.05.013
[Indexed for MEDLINE]

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