Synthetic Naphthoquinone Inhibits Herpes Simplex Virus Type-1 Replication Targeting Na+, K+ ATPase.
ACS Omega
; 9(34): 36835-36846, 2024 Aug 27.
Article
em En
| MEDLINE
| ID: mdl-39220530
ABSTRACT
Since 1970 acyclovir (ACV) has been the reference drug in treating herpes simplex virus (HSV) infections. However, resistant herpes simplex virus type 1 (HSV-1) strains have emerged, narrowing the treatment efficacy. The antiviral activity of classical Na+, K+ ATPase enzyme (NKA) inhibitors linked the viral replication to the NKA's activity. Herein, we evaluated the anti-HSV-1 activity of synthetic naphthoquinones, correlating their antiviral activity with NKA inhibition. We tested seven synthetic naphthoquinones initially at 50 µM on HSV-1-infected African green monkey kidney cells (VERO cells). Only one compound, 2-hydroxy-3-(2-thienyl)-1,4-naphthoquinone (AN-06), exhibited higher antiviral activity with a low cytotoxicity. AN-06 reduced the viral titer of 9 (log10) to 1.32 (log10) and decreased the steps of attachment and penetration. The addition of AN-06 up to 20 h postinfection (hpi) interfered with the viral cycle. The viral infection alone increases NKA activity 3 h postinfection (hpi), scaling up to 6 hpi. The addition of AN-06 in a culture infected with HSV-1 decreased NKA activity, suggesting that its antiviral action is linked to NKA inhibition. Also, docking results showed that this compound binds at the same site of NKA in which adenosine triphosphate (ATP) binds. AN-06 exhibited promising pharmacokinetic and toxicology properties. Thus, we postulate that AN-06 may be a good candidate for antiviral compounds with a mechanism of action targeting NKA activity.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
ACS Omega
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Brasil
País de publicação:
Estados Unidos