A novel flavivirus entry inhibitor, BP34610, discovered through high-throughput screening with dengue reporter viruses

Yang, Ching‐Fen; Hu, Han-Shu; Lin, Hui-Mei; Wu, Pei-Shan; Wu, Ren-Huang; Tian, Jia-Ni; Wu, Szu-Huei; Tsou, Lun K.; Song, Jen‐Shin; Chen, Hsin–Wei; Chern, Jyh-Haur; Chen, Chiung‐Tong; Yueh, Andrew

doi:10.1016/j.antiviral.2019.104636

Cited by 10 publications

(7 citation statements)

References 51 publications

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“…The target could be the N-terminal stem region of the E protein, of which the S397 site is crucial for the interaction between BP34610 and the DENV E protein. The mutation of S397P causes DENV2 to resist BP34610 [ 44 ]. Given the sequence similarity between the JEV and DENV E proteins, it is speculated that the target of BP34610 against JEV infection may also be the E protein, but more details of this must be revealed.…”

Section: Antivirals Against Jev Infectionmentioning

confidence: 99%

Recent Advances in Antivirals for Japanese Encephalitis Virus

Zhu

Chen

Lurong

et al. 2023

Viruses

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Culex mosquitoes are the primary vectors of the Japanese encephalitis virus (JEV). Since its discovery in 1935, Japanese encephalitis (JE), caused by JEV, has posed a significant threat to human health. Despite the widespread implementation of several JEV vaccines, the transmission chain of JEV in the natural ecosystem has not changed, and the vector of transmission cannot be eradicated. Therefore, JEV is still the focus of attention for flaviviruses. At present, there is no clinically specific drug for JE treatment. JEV infection is a complex interaction between the virus and the host cell, which is the focus of drug design and development. An overview of antivirals that target JEV elements and host factors is presented in this review. In addition, drugs that balance antiviral effects and host protection by regulating innate immunity, inflammation, apoptosis, or necrosis are reviewed to treat JE effectively.

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Section: Antivirals Against Jev Infectionmentioning

confidence: 99%

Recent Advances in Antivirals for Japanese Encephalitis Virus

Zhu

Chen

Lurong

et al. 2023

Viruses

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“…Besides synthetic peptide, a small molecule, BP34610, also displayed an inhibitory effect on all four dengue serotypes by targeting the E protein. Besides being capable of affecting the early stage of viral entry, this inhibitor portrays a synergistic effect with ribavirin against DENV [52].…”

Section: E Proteinmentioning

confidence: 99%

Updates on Dengue Vaccine and Antiviral: Where Are We Heading?

2021

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Approximately 100–400 million people from more than 100 countries in the tropical and subtropical world are affected by dengue infections. Recent scientific breakthroughs have brought new insights into novel strategies for the production of dengue antivirals and vaccines. The search for specific dengue inhibitors is expanding, and the mechanisms for evaluating the efficacy of novel drugs are currently established, allowing for expedited translation into human trials. Furthermore, in the aftermath of the only FDA-approved vaccine, Dengvaxia, a safer and more effective dengue vaccine candidate is making its way through the clinical trials. Until an effective antiviral therapy and licensed vaccine are available, disease monitoring and vector population control will be the mainstays of dengue prevention. In this article, we highlighted recent advances made in the perspectives of efforts made recently, in dengue vaccine development and dengue antiviral drug.

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“…Many natural products also demonstrated antiviral efficacy against other flavivirus members, including DENV and WNV [265][266][267][268]. In addition, niclosamide [245], tyrphostin A9 [245], BP34610 [234], and nanchangmycin [133] have been shown to have antiviral activities. Niclosamide, an antiparasitic drug [247], and tyrphostin A9, an RTK inhibitor [269], were identified as the most potent broad-spectrum compounds in a screen for Semliki Forest virus (SFV) and DENV-2 antivirals that act at the step of virus entry [245].…”

Section: Targeting Endocytic Entry: An Avenue For Flavivirus Antiviralsmentioning

confidence: 99%

“…Tyrphostin A9 may impact cargo-receptor signaling during endocytosis based on the mechanisms of chemical analogues [270] while niclosamide appears to impact endosomal acidification [246,247], though these proposed mechanisms are not definitive [245]. Another DENV screen identified BP34610, a candidate with antiviral efficacy against DENV-1/2/3/4 as well as JEV [234]. Time-of-addition assays revealed a role for BP34610 in viral entry, and resistant viruses suggested the compound likely targets the virion, rather than a host pathway.…”

Section: Targeting Endocytic Entry: An Avenue For Flavivirus Antiviralsmentioning

confidence: 99%

Beyond the Surface: Endocytosis of Mosquito-Borne Flaviviruses

Carro

Cherry

2020

Viruses

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Flaviviruses are a group of positive-sense RNA viruses that are primarily transmitted through arthropod vectors and are capable of causing a broad spectrum of diseases. Many of the flaviviruses that are pathogenic in humans are transmitted specifically through mosquito vectors. Over the past century, many mosquito-borne flavivirus infections have emerged and re-emerged, and are of global importance with hundreds of millions of infections occurring yearly. There is a need for novel, effective, and accessible vaccines and antivirals capable of inhibiting flavivirus infection and ameliorating disease. The development of therapeutics targeting viral entry has long been a goal of antiviral research, but most efforts are hindered by the lack of broad-spectrum potency or toxicities associated with on-target effects, since many host proteins necessary for viral entry are also essential for host cell biology. Mosquito-borne flaviviruses generally enter cells by clathrin-mediated endocytosis (CME), and recent studies suggest that a subset of these viruses can be internalized through a specialized form of CME that has additional dependencies distinct from canonical CME pathways, and antivirals targeting this pathway have been discovered. In this review, we discuss the role and contribution of endocytosis to mosquito-borne flavivirus entry as well as consider past and future efforts to target endocytosis for therapeutic interventions.

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A novel flavivirus entry inhibitor, BP34610, discovered through high-throughput screening with dengue reporter viruses

Cited by 10 publications

References 51 publications

Recent Advances in Antivirals for Japanese Encephalitis Virus

Recent Advances in Antivirals for Japanese Encephalitis Virus

Updates on Dengue Vaccine and Antiviral: Where Are We Heading?

Beyond the Surface: Endocytosis of Mosquito-Borne Flaviviruses

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