Functional characterization of the NS2B/NS3 protease complex from seven viruses belonging to different groups inside the genus Flavivirus

Virus Research
Maël BessaudHugues J Tolou

Abstract

The genus Flavivirus, family Flaviviridae, comprises more than 70 viruses. Many of them cause severe, potentially fatal, human diseases. Human vaccines are available for only three viruses and no effective antiviral drug is available. In order to limit the consequences of infections with flaviviruses, a promising approach consists in developing specific compounds that target the virus-encoded NS2B/NS3 protease complex, which is crucial for the viral polyprotein processing. In order to develop such compounds active as antiviral drugs against several flaviviruses, identification of biochemical properties shared by proteases from different viruses is essential. In this work, the functional similarity between the proteases from seven flaviviruses belonging to different major groups was addressed by characterizing their enzymatic properties. For each virus, a catalytically active recombinant protease was designed and expressed as a hexahistidine-tagged protein. Chromogenic and fluorogenic substrates were used to identify optimal conditions for proteolysis. Our study identified important physico-chemical properties shared by all the seven proteases we studied (high pH value requirement for optimal activity, inhibition of substrate pr...Continue Reading

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Citations

Sep 30, 2009·PLoS Neglected Tropical Diseases·Debapriya Ghosh, Anirban Basu
Jul 5, 2008·Drug Discovery Today·Debapriya Ghosh, Anirban Basu
Oct 27, 2007·Virus Research·Boris A M PastorinoMaël Bessaud
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Jan 8, 2015·Bioorganic & Medicinal Chemistry·Lorena Ramos Freitas de SousaPaulo Cezar Vieira
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Oct 18, 2016·F1000Research·Sean EkinsCarolina H Andrade
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Oct 13, 2006·The Journal of General Virology·Boris A M PastorinoMaël Bessaud
Feb 12, 2017·Biochemical and Biophysical Research Communications·Daniel Aguilera-Pesantes, Miguel A Méndez
Jul 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Agnieszka DabrowskaKrzysztof Pyrc
Jul 19, 2021·Molecular Aspects of Medicine·Kiran Bala SharmaManjula Kalia
Jul 25, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Teow Chong TeohHussin A Rothan

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