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Substrate specificity profiling of SARS-CoV-2 Mpro protease provides basis for anti-COVID-19 drug design

Wioletta Rut, Katarzyna Groborz, Linlin Zhang, Xinyuanyuan Sun, Mikolaj Zmudzinski, View ORCID ProfileRolf Hilgenfeld, Marcin Drag
doi: https://doi.org/10.1101/2020.03.07.981928
Wioletta Rut
aDepartment of Chemical Biology and Bioimaging, Wroclaw University of Science and Technology, Wyb. Wyspianskiego 27, 50-370 Wroclaw, Poland
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  • For correspondence: wioletta.rut@pwr.edu.pl marcin.drag@pwr.edu.pl
Katarzyna Groborz
aDepartment of Chemical Biology and Bioimaging, Wroclaw University of Science and Technology, Wyb. Wyspianskiego 27, 50-370 Wroclaw, Poland
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Linlin Zhang
bInstitute of Biochemistry, Center for Structural and Cell Biology in Medicine, University of Luebeck, Ratzeburger Allee 160, 23562 Luebeck, Germany
cGerman Center for Infection Research (DZIF), Hamburg-Luebeck-Borstel-Riems Site, University of Luebeck, 23562 Luebeck, Germany
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Xinyuanyuan Sun
bInstitute of Biochemistry, Center for Structural and Cell Biology in Medicine, University of Luebeck, Ratzeburger Allee 160, 23562 Luebeck, Germany
cGerman Center for Infection Research (DZIF), Hamburg-Luebeck-Borstel-Riems Site, University of Luebeck, 23562 Luebeck, Germany
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Mikolaj Zmudzinski
aDepartment of Chemical Biology and Bioimaging, Wroclaw University of Science and Technology, Wyb. Wyspianskiego 27, 50-370 Wroclaw, Poland
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Rolf Hilgenfeld
bInstitute of Biochemistry, Center for Structural and Cell Biology in Medicine, University of Luebeck, Ratzeburger Allee 160, 23562 Luebeck, Germany
cGerman Center for Infection Research (DZIF), Hamburg-Luebeck-Borstel-Riems Site, University of Luebeck, 23562 Luebeck, Germany
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  • ORCID record for Rolf Hilgenfeld
Marcin Drag
aDepartment of Chemical Biology and Bioimaging, Wroclaw University of Science and Technology, Wyb. Wyspianskiego 27, 50-370 Wroclaw, Poland
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  • For correspondence: wioletta.rut@pwr.edu.pl marcin.drag@pwr.edu.pl
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Abstract

In December 2019, the first cases of a novel coronavirus infection were diagnosed in Wuhan, China. Due to international travel and human-to-human transmission, the virus spread rapidly inside and outside of China. Currently, there is no effective antiviral treatment for COVID-19, therefore research efforts are focused on the rapid development of vaccines and antiviral drugs. The SARS-CoV-2 Mpro protease constitutes one of the most attractive antiviral drug targets. To address this emerging problem, we have synthesized a combinatorial library of fluorogenic substrates with glutamine in the P1 position. We used it to determine the substrate preferences of the SARS-CoV and SARS-CoV-2 proteases, using natural and a large panel of unnatural amino acids. The results of our work provide a structural framework for the design of inhibitors as antiviral agents or diagnostic tests.

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Posted March 08, 2020.
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Substrate specificity profiling of SARS-CoV-2 Mpro protease provides basis for anti-COVID-19 drug design
Wioletta Rut, Katarzyna Groborz, Linlin Zhang, Xinyuanyuan Sun, Mikolaj Zmudzinski, Rolf Hilgenfeld, Marcin Drag
bioRxiv 2020.03.07.981928; doi: https://doi.org/10.1101/2020.03.07.981928
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Substrate specificity profiling of SARS-CoV-2 Mpro protease provides basis for anti-COVID-19 drug design
Wioletta Rut, Katarzyna Groborz, Linlin Zhang, Xinyuanyuan Sun, Mikolaj Zmudzinski, Rolf Hilgenfeld, Marcin Drag
bioRxiv 2020.03.07.981928; doi: https://doi.org/10.1101/2020.03.07.981928

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