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Potential Role of Flavivirus NS2B-NS3 Proteases in Viral Pathogenesis and Anti-flavivirus Drug Discovery Employing Animal Cells and Models: A Review.
- Source :
-
Viruses [Viruses] 2021 Dec 28; Vol. 14 (1). Date of Electronic Publication: 2021 Dec 28. - Publication Year :
- 2021
-
Abstract
- Flaviviruses are known to cause a variety of diseases in humans in different parts of the world. There are very limited numbers of antivirals to combat flavivirus infection, and therefore new drug targets must be explored. The flavivirus NS2B-NS3 proteases are responsible for the cleavage of the flavivirus polyprotein, which is necessary for productive viral infection and for causing clinical infections; therefore, they are a promising drug target for devising novel drugs against different flaviviruses. This review highlights the structural details of the NS2B-NS3 proteases of different flaviviruses, and also describes potential antiviral drugs that can interfere with the viral protease activity, as determined by various studies. Moreover, optimized in vitro reaction conditions for studying the NS2B-NS3 proteases of different flaviviruses may vary and have been incorporated in this review. The increasing availability of the in silico and crystallographic/structural details of flavivirus NS2B-NS3 proteases in free and drug-bound states can pave the path for the development of promising antiflavivirus drugs to be used in clinics. However, there is a paucity of information available on using animal cells and models for studying flavivirus NS2B-NS3 proteases, as well as on the testing of the antiviral drug efficacy against NS2B-NS3 proteases. Therefore, on the basis of recent studies, an effort has also been made to propose potential cellular and animal models for the study of flavivirus NS2B-NS3 proteases for the purposes of exploring flavivirus pathogenesis and for testing the efficacy of possible drugs targets, in vitro and in vivo.
- Subjects :
- Animals
Dengue Virus
Drug Tapering
Encephalitis Virus, Japanese
Flavivirus genetics
Humans
Peptide Hydrolases genetics
Polyproteins
RNA Helicases genetics
Serine Endopeptidases genetics
Viral Nonstructural Proteins genetics
Viral Replicase Complex Proteins
West Nile virus
Yellow fever virus
Zika Virus
Antiviral Agents pharmacology
Drug Discovery
Flavivirus enzymology
Flavivirus Infections virology
Peptide Hydrolases metabolism
RNA Helicases metabolism
Serine Endopeptidases metabolism
Viral Nonstructural Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1999-4915
- Volume :
- 14
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Viruses
- Publication Type :
- Academic Journal
- Accession number :
- 35062249
- Full Text :
- https://doi.org/10.3390/v14010044