Nanoformulation of the Broad-Spectrum Hydrophobic Antiviral Vacuolar ATPase Inhibitor Diphyllin in Human Recombinant
SARS-CoV-2
TBEV
WNV
Zika virus
drug delivery
Journal
International journal of nanomedicine
ISSN: 1178-2013
Titre abrégé: Int J Nanomedicine
Pays: New Zealand
ID NLM: 101263847
Informations de publication
Date de publication:
2024
2024
Historique:
received:
28
11
2023
accepted:
08
04
2024
medline:
6
5
2024
pubmed:
6
5
2024
entrez:
6
5
2024
Statut:
epublish
Résumé
As highlighted by recent pandemic outbreaks, antiviral drugs are crucial resources in the global battle against viral diseases. Unfortunately, most antiviral drugs are characterized by a plethora of side effects and low efficiency/poor bioavailability owing to their insolubility. This also applies to the arylnaphthalide lignin family member, diphyllin (Diph). Diph acts as a vacuolar ATPase inhibitor and has been previously identified as a promising candidate with broad-spectrum antiviral activity. However, its physicochemical properties preclude its efficient administration in vivo, complicating preclinical testing. We produced human recombinant We revealed that loading into HsaFtH decreased the undesired cytotoxicity of Diph in mammalian host cells. We also confirmed that encapsulated Diph exhibited slightly lower antiviral activity than free Diph, which may be due to the differential uptake mechanism and kinetics of free Diph and Diph@HsaFtH. Furthermore, we confirmed that the antiviral effect was mediated solely by Diph with no contribution from HsaFtH. It was confirmed that HsaFtH is a suitable vehicle that allows easy loading of Diph and production of highly homogeneous nanoparticles dispersion with promising broad-spectrum antiviral activity.
Sections du résumé
Background
UNASSIGNED
As highlighted by recent pandemic outbreaks, antiviral drugs are crucial resources in the global battle against viral diseases. Unfortunately, most antiviral drugs are characterized by a plethora of side effects and low efficiency/poor bioavailability owing to their insolubility. This also applies to the arylnaphthalide lignin family member, diphyllin (Diph). Diph acts as a vacuolar ATPase inhibitor and has been previously identified as a promising candidate with broad-spectrum antiviral activity. However, its physicochemical properties preclude its efficient administration in vivo, complicating preclinical testing.
Methods
UNASSIGNED
We produced human recombinant
Results
UNASSIGNED
We revealed that loading into HsaFtH decreased the undesired cytotoxicity of Diph in mammalian host cells. We also confirmed that encapsulated Diph exhibited slightly lower antiviral activity than free Diph, which may be due to the differential uptake mechanism and kinetics of free Diph and Diph@HsaFtH. Furthermore, we confirmed that the antiviral effect was mediated solely by Diph with no contribution from HsaFtH.
Conclusion
UNASSIGNED
It was confirmed that HsaFtH is a suitable vehicle that allows easy loading of Diph and production of highly homogeneous nanoparticles dispersion with promising broad-spectrum antiviral activity.
Identifiants
pubmed: 38708183
doi: 10.2147/IJN.S452119
pii: 452119
pmc: PMC11069354
doi:
Substances chimiques
Antiviral Agents
0
diphyllin
W4PN5LDP26
Recombinant Proteins
0
Vacuolar Proton-Translocating ATPases
EC 3.6.1.-
Lignans
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3907-3917Informations de copyright
© 2024 Vojnikova et al.
Déclaration de conflit d'intérêts
The authors report no conflicts of interest in this work.