In vitro and in vivo characterization of erythrosin B and derivatives against Zika virus

Li, Zhong; Xu, Jimin; Lang, Yuekun; Wu, Xiangmeng; Hu, Saiyang; Samrat, Subodh Kumar; Tharappel, Anil Mathew; Kuo, Lili; Butler, David; Song, Yuanlin; Zhou, Jia; Li, Hongmin

doi:10.1016/j.apsb.2021.10.017

Cited by 15 publications

(13 citation statements)

References 48 publications

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“…ZIKV infection has been shown to impact the growth and size of forebrain organoids as well as the thickness of the ventricular zone layer (Qian et al 2016 ; Xu et al 2019 ). In addition, forebrain organoids have also been used as a platform to screen the anti-ZIKV activity of small molecule inhibitors (Xu et al 2016 ; Li et al 2020 , 2022 ). Infection studies in several brain organoid models have suggested that ZIKV can replicate in NPCs, astrocytes, and neurons that define the ZIKV neuropathology by mainly resulting in a general size reduction of organoids due to the defective differentiation/maturation and inducing cellular death (Garcez et al 2016 ; Cugola et al 2016 ; Dang et al 2016 ; Wells et al 2016 ; Gabriel et al 2017 ; Zhou et al 2017 ; Salick et al 2017 ; Liu et al 2019 ; Krenn et al 2021 ).…”

Section: Three-dimensional (3d) Brain Organoid Culturesmentioning

confidence: 99%

iPSC-derived three-dimensional brain organoid models and neurotropic viral infections

et al. 2023

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Progress in stem cell research has revolutionized the medical field for more than two decades. More recently, the discovery of induced pluripotent stem cells (iPSCs) has allowed for the development of advanced disease modeling and tissue engineering platforms. iPSCs are generated from adult somatic cells by reprogramming them into an embryonic-like state via the expression of transcription factors required for establishing pluripotency. In the context of the central nervous system (CNS), iPSCs have the potential to differentiate into a wide variety of brain cell types including neurons, astrocytes, microglial cells, endothelial cells, and oligodendrocytes. iPSCs can be used to generate brain organoids by using a constructive approach in three-dimensional (3D) culture in vitro. Recent advances in 3D brain organoid modeling have provided access to a better understanding of cell-to-cell interactions in disease progression, particularly with neurotropic viral infections. Neurotropic viral infections have been difficult to study in two-dimensional culture systems in vitro due to the lack of a multicellular composition of CNS cell networks. In recent years, 3D brain organoids have been preferred for modeling neurotropic viral diseases and have provided invaluable information for better understanding the molecular regulation of viral infection and cellular responses. Here we provide a comprehensive review of the literature on recent advances in iPSC-derived 3D brain organoid culturing and their utilization in modeling major neurotropic viral infections including HIV-1, HSV-1, JCV, ZIKV, CMV, and SARS-CoV2.

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Section: Three-dimensional (3d) Brain Organoid Culturesmentioning

confidence: 99%

iPSC-derived three-dimensional brain organoid models and neurotropic viral infections

et al. 2023

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“…Furthermore, compound 23 (erythrosin B) was found to be a potent orthosteric inhibitor of the NS2B-NS3 proteases of ZIKV and DENV-2 with IC 50 values of 1.7 μM and 1.9 μM, and EC 50 values of 0.62 μM and 1.2 μM, respectively [ 80 ]. SAR studies suggested that compound 23 derivative compound 24 (JMX0902, or Acid Red 94) was slightly more potent than the compound 23 in inhibition of ZIKV replication, with an EC 50 of 0.3 µM and a slightly reduced IC 50 of 2.6 µM [ 81 ]. The SAR studies indicated that iodine substitutions at R 1 and R 3 positions of the xanthene ring were critical for compound 23 ’s biological activities, whereas chlorine substitutions were tolerated on the isobenzofuran ring of compound 23 [ 81 ].…”

Section: Ns2b-ns3 Protease Inhibitorsmentioning

confidence: 99%

Antiviral Agents against Flavivirus Protease: Prospect and Future Direction

Samrat

et al. 2022

Pathogens

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Flaviviruses cause a significant amount of mortality and morbidity, especially in regions where they are endemic. A recent example is the outbreak of Zika virus throughout the world. Development of antiviral drugs against different viral targets is as important as the development of vaccines. During viral replication, a single polyprotein precursor (PP) is produced and further cleaved into individual proteins by a viral NS2B-NS3 protease complex together with host proteases. Flavivirus protease is one of the most attractive targets for development of therapeutic antivirals because it is essential for viral PP processing, leading to active viral proteins. In this review, we have summarized recent development in drug discovery targeting the NS2B-NS3 protease of flaviviruses, especially Zika, dengue, and West Nile viruses.

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“…Furthermore, compound 23 (erythrosin B (EB)) was found as a potent orthosteric inhibitor of the NS2B-NS3 proteases of ZIKV and DENV-2 with IC50 values of 1.7 µM and 1.9 µM, and EC50 values of 0.62 µM and 1.2 µM, respectively [72]. SAR studies suggested that compound 23 derivative compound 24 (JMX0902, or Acid Red 94) was slightly more potent than the compound 23 in inhibition of ZIKV replication, with an IC50 of 2.6 µMand EC50 of 0.3 µM [73]. The SAR studies indicated that iodine substitutions at R1 and R3 positions of the xanthene ring were essential for compound 23's biological activities, whereas chlorine substitutions were allowed on the isobenzofuran ring of compound 23 [73].…”

Section: Non-competitive Inhibitorsmentioning

confidence: 99%

“…SAR studies suggested that compound 23 derivative compound 24 (JMX0902, or Acid Red 94) was slightly more potent than the compound 23 in inhibition of ZIKV replication, with an IC50 of 2.6 µMand EC50 of 0.3 µM [73]. The SAR studies indicated that iodine substitutions at R1 and R3 positions of the xanthene ring were essential for compound 23's biological activities, whereas chlorine substitutions were allowed on the isobenzofuran ring of compound 23 [73].…”

Section: Non-competitive Inhibitorsmentioning

confidence: 99%

Antiviral Agents Against Flavivirus Protease: Prospect and Future Direction

Samrat¹,

Xu²,

Li³

et al. 2022

Preprint

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Flaviviruses cause a significant amount of mortality and morbidity, especially in the area where they are endemic. A recent example is the outbreak of Zika virus though out the world. Development of antiviral drugs against different viral targets is as important as development of vaccine. During viral replication, the flavivirus genome is translated as a single polyprotein precursor, which must be cleaved into individual proteins by a complex of the viral protease, NS3, and its cofactor, NS2B. Flavivirus protease is the most attractive target for development of therapeutic antivirals because it is essential for processing of viral polyprotein precursor and generation of functional viral proteins. In this review, we have summarized recent development in drug discovery targeting NS3-NS2B protease of flaviviruses, especially Zika, dengue and West Nile virus.

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In vitro and in vivo characterization of erythrosin B and derivatives against Zika virus

Cited by 15 publications

References 48 publications

iPSC-derived three-dimensional brain organoid models and neurotropic viral infections

iPSC-derived three-dimensional brain organoid models and neurotropic viral infections

Antiviral Agents against Flavivirus Protease: Prospect and Future Direction

Antiviral Agents Against Flavivirus Protease: Prospect and Future Direction

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