Drug screening identified gemcitabine inhibiting hepatitis E virus by inducing interferon-like response via activation of STAT1 phosphorylation

Mono- and combinational drug therapies for global viral pandemic preparedness

“…Interestingly, many predicted BCCs contain nucleotide/nucleoside analogs along with inhibitors of pyrimidine/purine biosynthesis, cap analogs, or IFNs, which also target viral RNA synthesis via IFN-induced RNases. Indeed, such combinations showed synergy in experiments performed in our and other laboratories ( Bellobuono et al., 1997 ; Byrn et al., 2015 ; Falloon et al., 2000 ; Herring et al., 2021 ; Ianevski et al., 2021a , 2021b ; Li et al., 2020 , 2022 ; Phillips et al., 2015 ; Pires de Mello et al., 2018 ; Schultz et al., 2022 ; Tong et al., 2018 ; Wedemeyer et al., 2013 ). Thus, our preliminary results suggest that scores could correlate with the antiviral efficacy of BCCs and that some of these combinations could be used as pan- and even cross-virus family .…”

“…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.…”

Recapitulating hepatitis E virus–host interactions and facilitating antiviral drug discovery in human liver–derived organoids

“…To provide proof of concept, we now screened a library of 94 known safe-in-human broad-spectrum antiviral agents in p6Luc organoids (table S2). We previously have screened this library in cancer line–based viral infection models ( 36 , 37 ). In this study, we used a low concentration (2.5 μM) to minimize nonspecific effects.…”

Broad-spectrum mono- and combinational drug therapies for global viral pandemic preparedness

“…Recently, we have tested several experimental, investigational, and approved BSAs against different viruses. We identified novel activities for saliphenylhalamide, gemcitabine, obatoclax, SNS-032, flavopiridole, 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 [27][28][29][30][31][32][33][34][35][36][37][38][39][40][41]. These results suggest that the landscape of BSA activities is vast and that it can and should be further interrogated and expanded.…”