Mechanisms of Action of the Host-Targeting Agent Cyclosporin A and Direct-Acting Antiviral Agents against Hepatitis C Virus.
NS5A
cyclophilin A
cyclosporin
hepatitis C virus
host-targeting agents
Journal
Viruses
ISSN: 1999-4915
Titre abrégé: Viruses
Pays: Switzerland
ID NLM: 101509722
Informations de publication
Date de publication:
17 04 2023
17 04 2023
Historique:
received:
10
02
2023
revised:
30
03
2023
accepted:
04
04
2023
medline:
1
5
2023
pubmed:
28
4
2023
entrez:
28
4
2023
Statut:
epublish
Résumé
Several direct-acting antivirals (DAAs) are available, providing interferon-free strategies for a hepatitis C cure. In contrast to DAAs, host-targeting agents (HTAs) interfere with host cellular factors that are essential in the viral replication cycle; as host genes, they are less likely to rapidly mutate under drug pressure, thus potentially exhibiting a high barrier to resistance, in addition to distinct mechanisms of action. We compared the effects of cyclosporin A (CsA), a HTA that targets cyclophilin A (CypA), to DAAs, including inhibitors of nonstructural protein 5A (NS5A), NS3/4A, and NS5B, in Huh7.5.1 cells. Our data show that CsA suppressed HCV infection as rapidly as the fastest-acting DAAs. CsA and inhibitors of NS5A and NS3/4A, but not of NS5B, suppressed the production and release of infectious HCV particles. Intriguingly, while CsA rapidly suppressed infectious extracellular virus levels, it had no significant effect on the intracellular infectious virus, suggesting that, unlike the DAAs tested here, it may block a post-assembly step in the viral replication cycle. Hence, our findings shed light on the biological processes involved in HCV replication and the role of CypA.
Identifiants
pubmed: 37112961
pii: v15040981
doi: 10.3390/v15040981
pmc: PMC10143304
pii:
doi:
Substances chimiques
Antiviral Agents
0
Cyclosporine
83HN0GTJ6D
Viral Nonstructural Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIAID NIH HHS
ID : R01 AI099284
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI120860
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI132833
Pays : United States
Organisme : NIGMS NIH HHS
ID : GM103368
Pays : United States
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