Structure and function of Zika virus NS5 protein: perspectives for drug design

Autor: Jikui Song, Rong Hai, Boxiao Wang, Stephanie Thurmond
Rok vydání: 2018
Předmět:
Models
Molecular
0301 basic medicine
Physiology
viruses
Viral Nonstructural Proteins
Genome
Antiviral inhibitors
Zika virus
chemistry.chemical_compound
Interferon
Models
RNA polymerase
Viral replication
2.2 Factors relating to the physical environment
Aetiology
biology
Drug discovery
Zika Virus Infection
Flavivirus
Infectious Diseases
Molecular Medicine
Infection
medicine.drug
Protein Binding
Biochemistry & Molecular Biology
030106 microbiology
Clinical Sciences
Pathogen–host interaction
RNA capping
Antiviral Agents
Article
Vaccine Related
03 medical and health sciences
Cellular and Molecular Neuroscience
Flaviviridae
Biodefense
medicine
Genetics
Animals
Humans
Molecular Biology
Pharmacology
Non-structural protein 5
Prevention
Molecular
Cell Biology
Zika Virus
biology.organism_classification
Virology
Pathogen-host interaction
030104 developmental biology
Emerging Infectious Diseases
Good Health and Well Being
chemistry
Drug Design
Biochemistry and Cell Biology
Zdroj: Cellular and molecular life sciences : CMLS, vol 75, iss 10
Popis: Zika virus (ZIKV) belongs to the positive-sense single-stranded RNA-containing Flaviviridae family. Its recent outbreak and association with human diseases (e.g. neurological disorders) have raised global health concerns, and an urgency to develop a therapeutic strategy against ZIKV infection. However, there is no currently approved antiviral against ZIKV. Here we present a comprehensive overview on recent progress in structure-function investigation of ZIKV NS5 protein, the largest non-structural protein of ZIKV, which is responsible for replication of the viral genome, RNA capping and suppression of host interferon responses. Structural comparison of the N-terminal methyltransferase (MTase) domain and C-terminal RNA dependent RNA polymerase (RdRP) domain of ZIKV NS5 with their counterparts from related viruses provides mechanistic insights into ZIKV NS5-mediated RNA replication, and identifies residues critical for its enzymatic activities. Finally, a collection of recently identified small molecule inhibitors against ZIKV NS5 or its closely related flavivirus homologues are also discussed.
Databáze: OpenAIRE
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