Strategies Towards Protease Inhibitors for Emerging Flaviviruses

Advances in Experimental Medicine and Biology
Christoph Nitsche

Abstract

Infections with flaviviruses are a continuing public health threat. In addition to vaccine development and vector control, the search for antiviral agents that alleviate symptoms in patients are of considerable interest. Among others, the flaviviral protease NS2B-NS3 is a promising drug target to inhibit viral replication. Flaviviral proteases share a high degree of structural similarity and substrate-recognition profile, which may facilitate a strategy towards development of pan-flaviviral protease inhibitors. However, the success of various drug discovery attempts during the last decade has been limited by the nature of the viral enzyme as well as a lack of robust structural templates. Small-molecular, structurally diverse protease inhibitors have been reported to reach affinities in the lower micromolar range. Peptide-based, substrate-derived compounds are often nanomolar inhibitors, however, with highly compromised drug-likeness. With some exceptions, the antiviral cellular activity of most of the reported compounds have been patchy and insufficient for further development. Recent progress has been made in the elucidation of inhibitor binding using different structural methods. This will hopefully lead to more rational atte...Continue Reading

Citations

Feb 27, 2019·Biophysics Reviews·Christoph Nitsche
May 6, 2020·Nature Microbiology·Theodore C Pierson, Michael S Diamond
Sep 21, 2019·Current Drug Targets·Dhurvas Chandrasekaran DineshEvžen Bouřa
Nov 17, 2020·Frontiers in Pharmacology·Xiangling CuiShan Cen
Apr 15, 2021·Journal of Medicinal Chemistry·Nikos KühlChristian D Klein
Jun 25, 2021·Chemical Science·Richard Morewood, Christoph Nitsche
Feb 21, 2019·ACS Medicinal Chemistry Letters·Christoph NitscheGottfried Otting
Aug 31, 2021·RSC Medicinal Chemistry·Saan Voss, Christoph Nitsche
Jan 1, 2019·Antiviral Research·Siew Pheng Lim

❮ Previous
Next ❯

Methods Mentioned

BETA
X-ray
NMR
protease assay
imaging techniques

Related Concepts

Related Feeds

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.