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 |
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Erscheinungsjahr: |
2014 |
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Erschienen: |
2014 |
Enthalten in: |
Zur Gesamtaufnahme - volume:18 |
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Enthalten in: |
Virologie (Montrouge, France) - 18(2014), 3 vom: 01. Juni, Seite 136-150 |
Sprache: |
Englisch |
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Weiterer Titel: |
Compréhension des mécanismes d’initiation de la synthèse des ARN viraux : vers la découverte de nouveaux inhibiteurs |
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Beteiligte Personen: |
Deval, Jerome [VerfasserIn] |
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Links: |
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Themen: |
Antivirals |
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Anmerkungen: |
Date Revised 19.10.2020 published: Print Citation Status PubMed-not-MEDLINE |
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doi: |
10.1684/vir.2014.0567 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM316353116 |
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520 | |a 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 | ||
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