The Clinically Approved Antifungal Drug Posaconazole Inhibits Human Cytomegalovirus Replication.
HCMV
antiviral
antiviral agents
drug repurposing
human CYP51
human cytomegalovirus
posaconazole
synergism
Journal
Antimicrobial agents and chemotherapy
ISSN: 1098-6596
Titre abrégé: Antimicrob Agents Chemother
Pays: United States
ID NLM: 0315061
Informations de publication
Date de publication:
21 09 2020
21 09 2020
Historique:
received:
10
01
2020
accepted:
11
05
2020
pubmed:
22
7
2020
medline:
22
6
2021
entrez:
22
7
2020
Statut:
epublish
Résumé
Posaconazole (PCZ) is a clinically approved drug used predominantly for prophylaxis and salvage therapy of fungal infections. Here, we report its previously undescribed anti-human cytomegalovirus (HCMV) activity. By using antiviral assays, we demonstrated that PCZ, along with other azolic antifungals, has a broad anti-HCMV activity, being active against different strains, including low-passage-number clinical isolates and strains resistant to viral DNA polymerase inhibitors. Using a pharmacological approach, we identified the inhibition of human cytochrome P450 51 (hCYP51), or lanosterol 14α demethylase, a cellular target of posaconazole in infected cells, as a mechanism of anti-HCMV activity of the drug. Indeed, hCYP51 expression was stimulated upon HCMV infection, and the inhibition of its enzymatic activity by either the lanosterol analog VFV {(
Identifiants
pubmed: 32690644
pii: AAC.00056-20
doi: 10.1128/AAC.00056-20
pmc: PMC7508619
pii:
doi:
Substances chimiques
Antifungal Agents
0
Antiviral Agents
0
Pharmaceutical Preparations
0
Triazoles
0
posaconazole
6TK1G07BHZ
Ganciclovir
P9G3CKZ4P5
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM067871
Pays : United States
Informations de copyright
Copyright © 2020 American Society for Microbiology.
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