The multi-targeted kinase inhibitor sorafenib inhibits enterovirus 71 replication by regulating IRES-dependent translation of viral proteins

Gao, Meng; Duan, Hao; Liu, Jing; Zhang, Hao; Wang, Xin; Zhu, Meng; Guo, James C. Y.; Zhao, Zhenlong; Li, Meng; Peng, Yiru

doi:10.1016/j.antiviral.2014.03.009

Cited by 24 publications

(16 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Despite the lower SI found in these cells compared with that found in MA104 cells, LJ04 effectively inhibited EV71 proliferation in HM1900 cells, and the expression of EV71 VP1 was inhibited by this polysaccharide in both MA104 and HM1900 cells. Antiviral mechanisms are complex systems, and the potential antiviral mechanisms that have been previously identified in vitro include the following: (i) a drug can directly interfere the binding between cells and viral particles, (ii) a drug can regulate antivirus‐related signaling pathways and cytokines, and (iii) a drug can directly suppress the activity of nonstructural proteins or the proliferation of viruses …”

Section: Discussionmentioning

confidence: 56%

“…Antiviral mechanisms are complex systems, and the potential antiviral mechanisms that have been previously identified in vitro include the following: (i) a drug can directly interfere the binding between cells and viral particles, [40][41][42] (ii) a drug can regulate antivirus-related signaling pathways and cytokines, [43][44][45][46] and (iii) a drug can directly suppress the activity of nonstructural proteins or the proliferation of viruses. [47][48][49] This study found that LJ04 is mainly composed of fucose, galactose, and mannose and can be considered a typical acidic polysaccharide, specifically a unique watersoluble polysaccharide with negative charge. As reported previously, the sulfuric acid group is critical for polysaccharide virucidal activity 50 and can either provide or enhance the virucidal activity of a polysaccharide through interaction with viral proteins, which might be due to attraction between the negatively charged sulfate group and the positively charged amino groups on the surface of viral F I G U R E 8 LJ04 blocked the binding of EV71 to MA104 cells.…”

Section: Discussionmentioning

confidence: 94%

See 1 more Smart Citation

Virucidal activity and the antiviral mechanism of acidic polysaccharides against Enterovirus 71 infectionin vitro

Cui

Liu

et al. 2020

Microbiology and Immunology

View full text Add to dashboard Cite

Enterovirus 71 (EV71) is the predominant pathogen for severe hand, foot, and mouth disease (HFMD) in children younger than 5 years, and currently no effective drugs are available for EV71. Thus, there is an urgent need to develop new drugs for the control of EV71 infection. In this study, LJ04 was extracted from Laminaria japonica using diethylaminoethyl cellulose‐52 with 0.4 mol/l NaCl as the eluent, and its virucidal activity was evaluated based on its cytopathic effects on a microplate. LJ04 is composed of fucose, galactose, and mannose and mainly showed good virucidal activity against EV71. The antiviral mechanisms of LJ04 were the direct inactivation of the virus, the blockage of virus binding, disruptions to viral entry, and weak inhibitory activity against the nonstructural protein 3C. The two most important findings from this study were that LJ04 inhibited EV71 proliferation in HM1900 cells, which are a human microglia cell line, and that LJ04 can directly inactivate EV71 within 2 hr at 37°C. This study demonstrates for the first time the ability of a polysaccharide from L. japonica to inhibit viral and 3C activity; importantly, the inhibition of 3C might have a minor effect on the antiviral effect of LJ04. Consequently, our results identify LJ04 as a potential drug candidate for the control of severe EV71 infection in clinical settings.

show abstract

Section: Discussionmentioning

confidence: 56%

Section: Discussionmentioning

confidence: 94%

Virucidal activity and the antiviral mechanism of acidic polysaccharides against Enterovirus 71 infectionin vitro

Cui

Liu

et al. 2020

Microbiology and Immunology

View full text Add to dashboard Cite

show abstract

“…Sorafenib is a small-molecule tyrosine kinase inhibitor that curbs angiogenesis in cancer patients [109]. In an attempt of repurposing cancer drugs as antivirals, sorafenib has been highlighted as a broad-range antiviral against adenovirus, mumps virus, chikungunya virus, dengue virus, West Nile virus, Yellow fever virus, and enterovirus 71 [110][111][112][113][114][115][116]. When administered at non-cytotoxic levels, however, sorafenib given in combination with IFN-β reduced RABV load by less than one order of magnitude (74% inhibition) [22].…”

Section: Host-directed Rabv Inhibitorsmentioning

confidence: 99%

Status of antiviral therapeutics against rabies virus and related emerging lyssaviruses

Pont

Plemper

Schnell

2019

Current Opinion in Virology

View full text Add to dashboard Cite

Rabies virus (RABV) constitutes a major social and economic burden associated with 60,000 deaths annually worldwide. Although pre-and post-exposure treatment options are available, they are efficacious only when initiated prior to the onset of clinical symptoms. Aggravating the problem, the current RABV vaccine does not cross-protect against the emerging zoonotic phylogroup II lyssaviruses. A requirement for an uninterrupted cold chain and high cost of the immunoglobulin component of rabies prophylaxis generate an unmet need for the development of RABV-specific antivirals. We discuss desirable anti-RABV drug profiles, past efforts to address the problem and inhibitor candidates identified, and examine how the rapidly expanding structural insight into RABV protein organization has illuminated novel druggable target candidates and paved the way to structure-aided drug optimization. Special emphasis is given to the viral RNAdependent RNA polymerase complex as a promising target for direct-acting broad-spectrum RABV inhibitors.

show abstract

“…Their data further showed that mutations in viral 3A and 3D polymerase regions could confer resistance against NITD008, suggesting an intimate crosstalk between 3A and 3D during viral replication. Sorafenib, previously known as BAY 43-9006 and marketed commercially as Nexavar, is a multi-target tyrosine and serine-threonine kinase inhibitor currently used in cancer therapy [84] . A significant reduction of infectious HEV71 titres and viral RNA was observed in infected cells when sorafenib was added 1 and 3 h postinfection.…”

Section: Post-infection Inhibitorsmentioning

confidence: 99%

“…A previous study has shown that HEV71 infection induced cyclooxygenase-2 (COX-2)/prostaglandins (PG) E2 expression via mitogen-activated protein kinases (MAPKs) including ERK and p38, and further that inhibition of HEV71-induced COX-2/PGE2 expression may reduce CNS inflammation [85] . Thus it was proposed that sorafenib treatment may alleviate HEV71-induced inflammatory responses [84] . Further in vivo studies are required to validate the effectiveness of the drug.…”

Section: Post-infection Inhibitorsmentioning

confidence: 99%

Therapeutic and prevention strategies against human enterovirus 71 infection

Kok

2015

WJV

View full text Add to dashboard Cite

Human enterovirus 71 (HEV71) is the cause of hand, foot and mouth disease and associated neurological complications in children under five years of age. There has been an increase in HEV71 epidemic activity throughout the Asia-Pacific region in the past decade, and it is predicted to replace poliovirus as the extant neurotropic enterovirus of highest global public health significance. To date there is no effective antiviral treatment and no vaccine is available to prevent HEV71 infection. The increase in prevalence, virulence and geographic spread of HEV71 infection over the past decade provides increasing incentive for the development of new therapeutic and prevention strategies against this emerging viral infection. The current review focuses on the potential, advantages and disadvantages of these strategies. Since the explosion of outbreaks leading to large epidemics in China, research in natural therapeutic products has identified several groups of compounds with anti-HEV71 activities. Concurrently, the search for effective synthetic antivirals has produced promising results. Other therapeutic strategies including immunotherapy and the use of oligonucleotides have also been explored. A sound prevention strategy is crucial in order to control the spread of HEV71. To this end the ultimate goal is the rapid development, regulatory approval and widespread implementation of a safe and effective vaccine. The various forms of HEV71 vaccine designs are highlighted in this review. Given the rapid progress of research in this area, eradication of the virus is likely to be achieved. Core tip: This review focuses on therapeutic and prevention strategies for the control of human enterovirus 71 infection. Therapeutic strategies highlighted include natural products, synthetic antivirals, immunotherapy, and the use of olignucleotides. Prevention strategies such as surveillance, physical prevention, and vaccine development form the second part of the review.Kok CC. Therapeutic and prevention strategies against human enterovirus 71 infection. World J Virol 2015; 4(2): 78-95 Available from:

show abstract

The multi-targeted kinase inhibitor sorafenib inhibits enterovirus 71 replication by regulating IRES-dependent translation of viral proteins

Cited by 24 publications

References 26 publications

Virucidal activity and the antiviral mechanism of acidic polysaccharides against Enterovirus 71 infectionin vitro

Virucidal activity and the antiviral mechanism of acidic polysaccharides against Enterovirus 71 infectionin vitro

Status of antiviral therapeutics against rabies virus and related emerging lyssaviruses

Therapeutic and prevention strategies against human enterovirus 71 infection

Contact Info

Product

Resources

About