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

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.

SUBMITTER: Kumar V

PROVIDER: S-EPMC7079562 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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

Kumar Vathan V Tan Kian-Pin KP Wang Ying-Ming YM Lin Sheng-Wei SW Liang Po-Huang PH

Bioorganic & medicinal chemistry 20160512 13

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 s ...[more]

PMID: 27240464

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