Understanding the mechanisms of viral RNA synthesis : towards the discovery of new inhibitors

In single-stranded RNA viruses, the initiation of RNA synthesis by the viral polymerases is a key step to the replication and transcription of the genetic material. RNA-dependent RNA polymerases (RdRps) have evolved independently for each virus family to recognize the 3'-end of viral genomes, maintain the integrity and the functionality of copied RNA, and to evade the recognition of foreign nucleic acid by host innate immune response. A better understanding of the underlying mechanisms governing the enzymatic activities involved in RNA initiation has enabled the discovery of small molecule inhibitors that can block virus replication and can be developed for therapeutic application. In this review, we present examples of such mechanisms for three unrelated single-stranded RNA virus families. In the first case, we show how blocking a conformation change of hepatitis C virus polymerase prevents the formation of the elongation complex. The second example describes inhibitors of the cap formation in Mononegavirales. In the third case, the inhibition of the endonuclease activity of the PA protein prevents the cap-snatching step of viral transcription by the RNA polymerase of Orthomyxoviruses.

Medienart:

E-Artikel

Erscheinungsjahr:

2014

Erschienen:

2014

Enthalten in:

Zur Gesamtaufnahme - volume:18

Enthalten in:

Virologie (Montrouge, France) - 18(2014), 3 vom: 01. Juni, Seite 136-150

Sprache:

Englisch

Weiterer Titel:

Compréhension des mécanismes d’initiation de la synthèse des ARN viraux : vers la découverte de nouveaux inhibiteurs

Beteiligte Personen:

Deval, Jerome [VerfasserIn]

Links:

Volltext

Themen:

Antivirals
Cap
Elongation
Flaviviridae
Hepatitis C virus
Influenza
Inhibition
Initiation
Journal Article
Orthomyxoviridae
Paramyxoviridae
RNA polymerase
RdRp
Respiratory syncytial virus
VSV

Anmerkungen:

Date Revised 19.10.2020

published: Print

Citation Status PubMed-not-MEDLINE

doi:

10.1684/vir.2014.0567

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM316353116