N-Acetyl cysteine effectively alleviates Coxsackievirus B-Induced myocarditis through suppressing viral replication and inflammatory response.
Acetylcysteine
/ therapeutic use
Animals
Animals, Newborn
Antiviral Agents
/ therapeutic use
Caspase Inhibitors
/ therapeutic use
Coxsackievirus Infections
/ complications
Enterovirus B, Human
/ drug effects
HeLa Cells
Humans
Inflammation
/ drug therapy
Mice, Inbred BALB C
Myocarditis
/ drug therapy
Proteasome Endopeptidase Complex
/ metabolism
Specific Pathogen-Free Organisms
Virus Replication
/ drug effects
Antiviral
Caspase-1
Coxsackievirus B
N-acetyl cysteine
Viral protease
Journal
Antiviral research
ISSN: 1872-9096
Titre abrégé: Antiviral Res
Pays: Netherlands
ID NLM: 8109699
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
21
08
2019
revised:
22
11
2019
accepted:
17
12
2019
pubmed:
31
12
2019
medline:
7
4
2021
entrez:
30
12
2019
Statut:
ppublish
Résumé
Viral myocarditis caused by Coxsackievirus B (CVB) infection is a severe inflammatory disease of the myocardium, which may develop to cardiomyopathy and heart failure. No effective specific treatment is available. Our previous study demonstrated that suppression of proinflammatory caspase-1 activation effectively inhibited CVB replication. N-acetyl cysteine (NAC) is a widely used antioxidant. In this study, we found that NAC significantly alleviated the myocardial injury caused by CVB type 3 (CVB3) under in vivo condition. Importantly, NAC treatment simultaneously suppressed viral replication and inflammatory response in both myocardium and cell culture. The antiviral and anti-inflammation mechanism of NAC, while independent of its antioxidant property, relies on its inhibition on caspase-1 activation. Moreover, NAC promotes procaspase-1 degradation via ubiquitin proteasome system, which further contributes to caspase-1 down-regulation. NAC also inhibits the activity of viral proteases. Taken together, this study shows that NAC exerts potent anti-CVB and anti-inflammation effect through targeting caspase-1. Given that NAC is a clinically approved medicine, we recommend NAC as a valuable therapeutic agent for viral myocarditis caused by CVB.
Identifiants
pubmed: 31883926
pii: S0166-3542(19)30473-5
doi: 10.1016/j.antiviral.2019.104699
pii:
doi:
Substances chimiques
Antiviral Agents
0
Caspase Inhibitors
0
Proteasome Endopeptidase Complex
EC 3.4.25.1
Acetylcysteine
WYQ7N0BPYC
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
104699Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest There is no conflict of interests in this work.