A new high-content screening assay of the entire hepatitis B virus life cycle identifies novel antivirals

Yang, Jaewon; König, Alexander; Park, Soonju; Jo, Eunji; Sung, Pil Soo; Yoon, Seung Kew; Žusinaite, Eva; Kainov, Denis E.; Shum, David; Windisch, Marc P.

doi:10.1016/j.jhepr.2021.100296

Cited by 5 publications

(4 citation statements)

References 20 publications

(20 reference statements)

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“…Recently, we have tested several experimental, investigational, and approved BSAs against different viruses. We identified novel activities for saliphenylhalamide, gemcitabine, obatoclax, SNS-032, flavopiridol, nelfinavir, salinomycin, amodiaquine, obatoclax, emetine, homoharringtonine, atovaquone and ciclesonide, dalbavancin, vemurafenib, MK-2206, ezetimibe, azacitidine, cyclosporine, minocycline, ritonavir, oritavancin, cidofovir, dibucaine, azithromycin, gefitinib, minocycline, pirlindole ivermectin, brequinar, homoharringtonine, azacytidine, itraconazole, lopinavir, nitazoxanide, umifenovir, sertraline, amodiaquine and aripiprazole ( Andersen et al., 2019 ; Bosl et al., 2019 ; Chen et al., 2020 ; Denisova et al., 2012 , 2014 ; Herring et al., 2021 ; Ianevski et al., 2018 , 2020c ; Kakkola et al., 2013 ; Ko et al., 2021 ; Kuivanen et al., 2017 ; Li et al., 2020 , 2021 ; Soderholm et al., 2016 ; Yang et al., 2021 ). These results suggest that the landscape of BSA activities is vast and that it can be further interrogated and expanded.…”

Section: The Landscape Of Broad-spectrum Antiviral Activities Can Be ...mentioning

confidence: 99%

Mono- and combinational drug therapies for global viral pandemic preparedness

et al. 2022

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Section: The Landscape Of Broad-spectrum Antiviral Activities Can Be ...mentioning

confidence: 99%

Mono- and combinational drug therapies for global viral pandemic preparedness

et al. 2022

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“…Additionally, clofarabine is employed as an anticancer therapy for several solid tumors, including bladder ( 43 ), stomach ( 44 ), and breast malignancies ( 45 ). Since fludarabine dramatically reduces the release of HBV progenitor DNA, it has been used to treat HBV infection and enhance the prognosis of HCC that is related to HBV ( 46 ). Combining fludarabine with fusion proteins comprising the poliovirus receptor (PVR) and the programmed death-1 (PD-1) extracellular structural domain improves long-term tumor-specific immunosurveillance and CD8+ T cell-mediated anticancer effects ( 47 ).…”

Section: Discussionmentioning

confidence: 99%

Combined analysis of bulk and single-cell RNA sequencing reveals novel natural killer cell-related prognostic biomarkers for predicting immunotherapeutic response in hepatocellular carcinoma

Zhang

Yuan

2023

Front. Immunol.

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IntroductionNatural killer (NK) cells play an irreplaceable and important role as a subtype of innate immune cells in the contemporary setting of antitumor immunity.MethodsWe chose a total of 1,196 samples for this analysis from the public dataset’s six separate cohorts. To identify 42 NK cell marker genes, we first carried out a thorough study of single-cell RNA sequencing data from the GSE149614 cohort of hepatocellular carcinoma (HCC).ResultsUsing the NK cell marker genes in the TCGA cohort, we next created a seven-gene prognostic signature, separating the patients into two categories with distinct survival patterns. This signature’s prognostic prediction ability was well verified across several validation cohorts. Patients with high scores had higher TIDE scores but lower immune cell infiltration percentages. Importantly, low-scoring patients had superior immunotherapy response and prognosis than high-scoring patients in an independent immunotherapy cohort (IMvigor210). Finally, we used CD56 and TUBA1B antibodies for immunohistochemical labeling of HCC tissue sections, and we discovered a lower number of CD56+ cells in the HCC tissue sections with high TUBA1B expression.DiscussionIn summary, our research created a unique prognostic profile based on NK cell marker genes that may accurately predict how well immunotherapy would work for HCC patients.

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“…Gemcitabine and hydroxyurea have broad-spectrum antiviral or anti-Ribonucleotide reductase activity [37,38]. Fludarabine can reduce the secretion of hepatitis B virus progeny DNA in HepG2-NTCPsec + cells [39]. Reasonably, these approved nucleoside analogs should reduce MPXV pathogenesis by decreasing MPXV DNA synthesis that are mediated by I4L.…”

Section: Discussionmentioning

confidence: 99%

Proteome-Based Investigation Identified Potential Drug Repurposable Small Molecules Against Monkeypox Disease

et al. 2022

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Monkeypox Virus (MPXV), the causative agent of Monkeypox (MPX) disease, is an emerging zoonotic pathogen spreading in different endemic and non-endemic nations and creating outbreaks. MPX treatment mainly includes Cidofovir and Tecovirimat but they have several side effects and solely depending on these drugs may promote the emergence of drug-resistant variants. Hence, new drugs are required to control the spread of the disease. In this study, we explored the MPXV proteome to suggest repurposable drugs. DrugBank screening revealed drugs such as Brinzolamide, Dorzolamide, Methazolamide, Zidovudine, Gemcitabine, Hydroxyurea, Fludarabine, and Tecovirimat as controls. Structural analogs of these compounds were extracted from ChEMBL Database. After Molecular docking and Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET)-based screening, we identified Zidovudine (binding affinity-5.9 kcal/mol) and a Harmala alkaloid (2S,4R)-4-(9H-Pyrido [3,4-b]indol-1-yl)-1,2,4-butanetriol (binding affinity − 6.6 kcal/mol) against L2R receptor (Thymidine Kinase). Moreover, Fludarabine (binding affinity − 6.4 kcal/mol) and 5′-Dehydroadenosine (binding affinity − 6.4 kcal/ mol) can strongly interact with the I4L receptor (Ribonucleotide reductase large subunit R1). Molecular Dynamics (MD) simulations suggest all of these compounds can change the C-alpha backbone, residue mobility, compactness, and solvent accessible surface area of L2R and I4L. Our results strongly suggest that these drug repurposing small molecules are worth exploring in vivo and in vitro for clinical applications.

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A new high-content screening assay of the entire hepatitis B virus life cycle identifies novel antivirals

Cited by 5 publications

References 20 publications

Mono- and combinational drug therapies for global viral pandemic preparedness

Mono- and combinational drug therapies for global viral pandemic preparedness

Combined analysis of bulk and single-cell RNA sequencing reveals novel natural killer cell-related prognostic biomarkers for predicting immunotherapeutic response in hepatocellular carcinoma

Proteome-Based Investigation Identified Potential Drug Repurposable Small Molecules Against Monkeypox Disease

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