Identification of filovirus entry inhibitors targeting the endosomal receptor NPC1 binding site

Wang, Leah Liu; Palermo, Nicholas Y.; Estrada, Leslie; Thompson, Colton; Patten, J.J.; Anantpadma, Manu; Davey, Robert A.; Xiang, Shi-Hua

doi:10.1016/j.antiviral.2021.105059

Cited by 4 publications

(2 citation statements)

References 38 publications

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“…Screening studies have identified various drugs with MARV entry-specific inhibition and synergistic effects on inhibiting viral entry ( Cheng et al, 2015 ; Zhang et al, 2020 ; Schafer et al, 2021 ). Additionally, compounds with potent inhibitory activity against both Ebola and Marburg viruses have been identified ( Wang et al, 2021 ) ( Table 1 ).…”

Section: Emerging Therapeutic Approaches For Marburg Virus Infectionmentioning

confidence: 99%

Novel antiviral approaches for Marburg: a promising therapeutics in the pipeline

Srivastava,

Kumar,

Ashique

et al. 2024

Front. Microbiol.

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Marburg virus disease (MVD) presents a significant global health threat, lacking effective antivirals and with current supportive care offering limited therapeutic options. This mini review explores the emerging landscape of novel antiviral strategies against MVD, focusing on promising therapeutics currently in the development pipeline. We delve into direct-acting antiviral approaches, including small molecule inhibitors targeting viral entry, replication, and assembly, alongside nucleic acid antisense and RNA interference strategies. Host-targeting antivirals are also considered, encompassing immune modulators like interferons and cytokine/chemokine modulators, broad-spectrum antivirals, and convalescent plasma and antibody-based therapies. The paper then examines preclinical and clinical development for the novel therapeutics, highlighting in vitro and in vivo models for antiviral evaluation, safety and efficacy assessments, and the critical stages of clinical trials. Recognizing the challenges of drug resistance and viral escape, the mini review underscores the potential of combination therapy strategies and emphasizes the need for rapid diagnostic tools to optimize treatment initiation. Finally, we discuss the importance of public health preparedness and equitable access to these promising therapeutics in achieving effective MVD control and global health security. This mini review presents a comprehensive overview of the burgeoning field of MVD antivirals, highlighting the potential of these novel approaches to reshape the future of MVD treatment and prevention.

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Section: Emerging Therapeutic Approaches For Marburg Virus Infectionmentioning

confidence: 99%

Novel antiviral approaches for Marburg: a promising therapeutics in the pipeline

Srivastava,

Kumar,

Ashique

et al. 2024

Front. Microbiol.

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“…Cathepsin inhibitors such as E-64 27 , 28 and AMS36 29 prevent GP from being cleaved into its fusion-active form. NPC1 binding and fusion can be inhibited by compounds such as compound 3.47, U18666A, MBX2254, MBX2270, SC198, SC073, and SC816 10 , 30 , 31 , 32 , 33 . Besides, a series of compounds, including toremifene, clomiphene, sertraline, bepridil, imipramine, clomipramine and thioridazine, were reported to inhibits fusion by destabilizing the stability of GP 34 , 35 , 36 .…”

Section: Introductionmentioning

confidence: 99%

Repurposing of berbamine hydrochloride to inhibit Ebola virus by targeting viral glycoprotein

Wang

et al. 2022

Acta Pharmaceutica Sinica B

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Filovirus helical nucleocapsid structures

Noda

2022

Microscopy

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Filoviruses are filamentous enveloped viruses belonging to the family Filoviridae, in the order Mononegavirales. Some filovirus members, such as Ebola virus (EBOV) and Marburg virus (MARV), cause severe hemorrhagic fever in humans and non-human primates. The filovirus ribonucleoprotein complex, called the nucleocapsid, forms a double-layered helical structure in which a non-segmented, single-stranded negative-sense RNA genome is encapsidated by nucleoprotein (NP), viral protein 35 (VP35), VP24, VP30, and RNA-dependent RNA polymerase (L). The inner layer consists of the helical NP–RNA complex, acting as a scaffold for the binding of VP35 and VP24 that constitute the outer layer. Recent structural studies using cryo-electron microscopy have advanced our understanding of the molecular mechanism of filovirus nucleocapsid formation. Here, we review the key characteristics of the EBOV and MARV nucleocapsid structures, highlighting the similarities and differences between the two viruses. In particular, we focus on the structure of the helical NP–RNA complex, the RNA binding mechanism, and the NP–NP interactions in the helix. The structural analyses reveal a possible mechanism of nucleocapsid assembly and provide potential targets for the anti-filovirus drug design. Mini-abstract Filovirus nucleocapsid is responsible for viral genome transcription and replication. Here, we summarize the helical nucleocapsid structure of Ebola and Marburg viruses, focusing on the nucleoprotein-RNA helix of the nucleocapsid core structure, which has been recently determined by cryo-electron microscopy.

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Identification of filovirus entry inhibitors targeting the endosomal receptor NPC1 binding site

Cited by 4 publications

References 38 publications

Novel antiviral approaches for Marburg: a promising therapeutics in the pipeline

Novel antiviral approaches for Marburg: a promising therapeutics in the pipeline

Repurposing of berbamine hydrochloride to inhibit Ebola virus by targeting viral glycoprotein

Filovirus helical nucleocapsid structures

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