Elucidation of the mechanism of anti-herpes action of two novel semisynthetic cardenolide derivatives.
Acyclovir
/ pharmacology
Animals
Antiviral Agents
/ chemical synthesis
Cardenolides
/ chemical synthesis
Chlorocebus aethiops
Drug Evaluation, Preclinical
Drug Resistance, Viral
Herpesviridae Infections
/ drug therapy
Herpesvirus 1, Human
/ drug effects
Herpesvirus 2, Human
/ drug effects
Humans
Vero Cells
Journal
Archives of virology
ISSN: 1432-8798
Titre abrégé: Arch Virol
Pays: Austria
ID NLM: 7506870
Informations de publication
Date de publication:
Jun 2020
Jun 2020
Historique:
received:
06
11
2019
accepted:
22
01
2020
pubmed:
30
4
2020
medline:
28
5
2020
entrez:
30
4
2020
Statut:
ppublish
Résumé
Human herpesviruses are among the most prevalent pathogens worldwide and have become an important public health issue. Recurrent infections and the emergence of resistant viral strains reinforce the need of searching new drugs to treat herpes virus infections. Cardiac glycosides are used clinically to treat cardiovascular disturbances, such as congestive heart failure and atrial arrhythmias. In recent years, they have sparked new interest in their potential anti-herpes action. It has been previously reported by our research group that two new semisynthetic cardenolides, namely C10 (3β-[(N-(2-hydroxyethyl)aminoacetyl]amino-3-deoxydigitoxigenin) and C11 (3β-(hydroxyacetyl)amino-3-deoxydigitoxigenin), exhibited potential anti-HSV-1 and anti-HSV-2 with selectivity index values > 1,000, comparable with those of acyclovir. This work reports the mechanism investigation of anti-herpes action of these derivatives. The results demonstrated that C10 and C11 interfere with the intermediate and final steps of HSV replication, but not with the early stages, since they completely abolished the expression of the UL42 (β) and gD (γ) proteins and partially reduced that of ICP27 (α). Additionally, they were not virucidal and had no prophylactic effects. Both compounds inhibited HSV replication at nanomolar concentrations, but cardenolide C10 was more active than C11 and can be considered as an anti-herpes drug candidate including against acyclovir-resistant HSV-1 strains.
Identifiants
pubmed: 32346764
doi: 10.1007/s00705-020-04562-1
pii: 10.1007/s00705-020-04562-1
pmc: PMC7188521
doi:
Substances chimiques
Antiviral Agents
0
Cardenolides
0
Acyclovir
X4HES1O11F
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1385-1396Subventions
Organisme : Fapemig
ID : APQ-00538-17
Organisme : Fapemig
ID : RMP
Organisme : CNPq
ID : 305878/2016-6
Organisme : CNPq
ID : 490057/2011-0
Organisme : Marie Curie Foundation/European Community
ID : 295251
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