Zinc finger antiviral protein inhibits coxsackievirus B3 virus replication and protects against viral myocarditis

Lithium chloride confers protection against viral myocarditis via suppression of coxsackievirus B3 virus replication, Microbial Pathogenesis, https://doi. Highlights Lithium chloride inhibits coxsackievirus B3 virus replication in vitro and in vivo.Lithium chloride inhibits CVB3 replication via inhibiting virus-induced cell apoptosis.LiCl treatment in vivo obviously alleviated CVB3-induced acute myocarditis. 3 Abstract Viral myocarditis (VMC) is a type of inflammation affecting myocardial cells caused by viral infection and has been an important cause of dilated cardiomyopathy (DCM) worldwide. Type B3 coxsackievirus (CVB3), a non-enveloped positive-strand RNA virus of the Enterovirus genus, is one of most common agent of viral myocarditis. Till now, effective treatments for VMC are lacking due to lack of drugs or vaccine. Lithium chloride (LiCl) is applied in the clinical management of manic depressive disorders. Accumulating evidence have demonstrated that LiCl, also as an effective antiviral drug, exhibited antiviral effects for specific viruses. However, there are few reports of evaluating LiCl's antiviral effect in mice model. Here, we investigated the inhibitory influence of LiCl on the CVB3 replication in vitro and in vivo and the development of CVB3-induced VMC. We found that LiCl significantly suppressed CVB3 replication in HeLa via inhibiting virus-induced cell apoptosis. Moreover, LiCl treatment in vivo obviously inhibited virus replication within the myocardium and alleviated CVB3-induced acute myocarditis. Collectively, our data demonstrated that LiCl inhibited CVB3 replication and negatively regulated virus-triggered inflammatory responses.Our finding further expands the antiviral targets of LiCl and provides an alternative agent for viral myocarditis. Conflict of interestThe authors declare no conflict of interest. Ethical approvalThe animal experiments were performed in accordance with Soochow University institutional guidelines, and the study was approved by the Ethics Committee of Soochow University in written form. Euthanasia of mice was performed by carbon dioxide inhalation with minimum fear, anxiety and pain. HighlightsLithium chloride inhibits coxsackievirus B3 virus replication in vitro and in vivo.

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“…The detailed protocol of RNA isolation, RT-PCR and primer sequences used were detailed in a previous report [16].…”

Section: Rna Extraction and Rt-pcrmentioning

confidence: 99%

“…SDS-PAGE and immunoblot analysis were performed as described previously [16,17]. The proteins extracted from HeLa cells or heart tissues were detected with anti-VP1 (Clone…”

Section: Western Blotmentioning

confidence: 99%

Lithium chloride confers protection against viral myocarditis via suppression of coxsackievirus B3 virus replication

Zhao

Yan

Wang

et al. 2020

Microbial Pathogenesis

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“…The host ZNF exhibits antiviral activity against positive-stranded RNA viruses (Togaviridae), negative-stranded RNA viruses (Filoviridae), and retroviruses (Retroviridae) (33). However, the relationships between ZNF623 or AZGP1 and RMPP have not been studied.…”

Section: Discussionmentioning

confidence: 99%

iTRAQ-based Quantitative Proteomics Study in Patients with Refractory <i>Mycoplasma pneumoniae</i> Pneumonia

Song

Xie

et al. 2017

Jpn J Infect Dis

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“…Host cells have developed an innate immune system to act as the first-line defense against invading virus. In addition, a series of intracellular restriction factors are also expressed endogenously to counteract viral infections, 197 and apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G (APOBEC3G, A3G) is one such factor, which possesses the capacity to restrict the replication of a panel of viruses including HIV-1, HBV, HCV, and EV71 among others via different mechanisms. A3G is known as a cytidine deaminase, catalyzing the irreversible hydrolytic deamination of cytidine and deoxycytidine to uridine and deoxyuridine, respectively.…”

Section: Apolipoprotein B Mrna-editing Enzyme Catalytic Polypeptidementioning

confidence: 99%

Medicinal chemistry strategies toward host targeting antiviral agents

2020

Medicinal Research Reviews

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Direct-acting antiviral agents (DAAs) represent a class of drugs targeting viral proteins and have been demonstrated to be very successful in combating viral infections in clinic. However, DAAs suffer from several inherent limitations, including narrow-spectrum antiviral profiles and liability to drug resistance, and hence there are still unmet needs in the treatment of viral infections. In comparison, host targeting antivirals (HTAs) target host factors for antiviral treatment. Since host proteins are probably broadly required for various viral infections, HTAs are not only perceived, but also demonstrated to exhibit broad-spectrum antiviral activities. In addition, host proteins are not under the genetic control of viral genome, and hence HTAs possess much higher genetic barrier to drug resistance as compared with DAAs. In recent years, much progress has been made to the development of HTAs with the approval of chemokine receptor type 5 antagonist maraviroc for human immunodeficiency virus treatment and more in the pipeline for other viral infections. In this review, we summarize various host proteins as antiviral targets from a medicinal chemistry prospective. Challenges and issues associated with HTAs are also discussed. K E Y W O R D S broad-spectrum antivirals, direct-acting antiviral agents, drug resistance, host targeting antiviral agents

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Zinc finger antiviral protein inhibits coxsackievirus B3 virus replication and protects against viral myocarditis

Cited by 43 publications

References 31 publications

Lithium chloride confers protection against viral myocarditis via suppression of coxsackievirus B3 virus replication

Lithium chloride confers protection against viral myocarditis via suppression of coxsackievirus B3 virus replication

iTRAQ-based Quantitative Proteomics Study in Patients with Refractory <i>Mycoplasma pneumoniae</i> Pneumonia

Medicinal chemistry strategies toward host targeting antiviral agents

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