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The flavivirus protease as a target for drug discovery

  • Review
  • Published:
Virologica Sinica

Abstract

Many flaviviruses are significant human pathogens causing considerable disease burdens, including encephalitis and hemorrhagic fever, in the regions in which they are endemic. A paucity of treatments for flaviviral infections has driven interest in drug development targeting proteins essential to flavivirus replication, such as the viral protease. During viral replication, the flavivirus genome is translated as a single polyprotein precursor, which must be cleaved into individual proteins by a complex of the viral protease, NS3, and its cofactor, NS2B. Because this cleavage is an obligate step of the viral life-cycle, the flavivirus protease is an attractive target for antiviral drug development. In this review, we will survey recent drug development studies targeting the NS3 active site, as well as studies targeting an NS2B/NS3 interaction site determined from flavivirus protease crystal structures.

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Authors and Affiliations

  1. Wadsworth Center, New York State Department of Health, 120 New Scotland Ave, Albany, NY, 12208, USA

    Matthew Brecher, Jing Zhang & Hongmin Li

  2. Department of Biomedical Sciences, School of Public Health, State University of New York, Empire State Plaza, PO Box 509, Albany, New York, 12201-0509, USA

    Hongmin Li

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  1. Matthew Brecher
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Correspondence to Hongmin Li.

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Brecher, M., Zhang, J. & Li, H. The flavivirus protease as a target for drug discovery. Virol. Sin. 28, 326–336 (2013). https://doi.org/10.1007/s12250-013-3390-x

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