Repurposing drugs as COVID-19 therapies: A toxicity evaluation

Ngan, Deborah K.; Xu, Tuan; Xia, Menghang; Zheng, Wei; Huang, Ruili

doi:10.1016/j.drudis.2022.04.001

Cited by 16 publications

(9 citation statements)

References 63 publications

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“…In any case, it is important to note that the concentrations of ivermectin under consideration are not achievable clinically at current recommended doses of <200µg/Kg 14,15,31 . Nonetheless, our findings further point towards CPE and/or cell based assays as, perhaps , more clinically relevant endpoints in screening therapeutics against SARS-CoV-2 5,11,32 .…”

Section: Discussionmentioning

confidence: 64%

Erythromycin, Retapamulin, Pyridoxine, Folic acid and Ivermectin dose dependently inhibit cytopathic effect, Papain-like Protease and M^PROof SARS-CoV-2

Bello

Imam

Bello

et al. 2022

Preprint

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We previously showed that Erythromycin, Retapamulin, Pyridoxine, Folic acid and Ivermectin inhibit SARS-COV-2 induced cytopathic effect (CPE) in Vero cells. In this study and using validated quantitative neutral red assay, we show that the inhibition of CPE is concentration dependent with Inhibitory Concentration-50(IC50) of 3.27 microM, 4.23 microM, 9.29 microM, 3.19 microM and 84.31 microM respectively. Furthermore, Erythromycin, Retapamulin, Pyridoxine, Folic acid and Ivermectin dose dependently inhibit SARS-CoV-2 Papain-like Protease with IC50 of 0.94 microM, 0.88 microM, 1.14 microM, 1.07 microM, 1.51 microM respectively and the main protease(MPRO) with IC50 of 1.35 microM, 1.25 microM, 7.36 microM, 1.15 microM, and 2.44 microM respectively. The IC50 for all the drugs, except ivermectin, are at the clinically achievable plasma concentration in human, which supports a possible role for the drugs in the management of COVID-19. The lack of inhibition of CPE by Ivermectin at clinical concentrations could be part of the explanation for its lack of effectiveness in clinical trials.

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Section: Discussionmentioning

confidence: 64%

Erythromycin, Retapamulin, Pyridoxine, Folic acid and Ivermectin dose dependently inhibit cytopathic effect, Papain-like Protease and M^PROof SARS-CoV-2

Bello

Imam

Bello

et al. 2022

Preprint

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“…Ciclopirox is a antifungal medication. According to some studies, ciclopirox has antibacterial and anti-inflammatory properties [113]. Ciclopirox may have appropriate application scenarios in COVID-19 patients with a fungal infection [114,115].…”

Section: Discussionmentioning

confidence: 99%

Systems biology approach reveals a common molecular basis for COVID-19 and non-alcoholic fatty liver disease (NAFLD)

et al. 2022

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Background Patients with non-alcoholic fatty liver disease (NAFLD) may be more susceptible to coronavirus disease 2019 (COVID-19) and even more likely to suffer from severe COVID-19. Whether there is a common molecular pathological basis for COVID-19 and NAFLD remains to be identified. The present study aimed to elucidate the transcriptional alterations shared by COVID-19 and NAFLD and to identify potential compounds targeting both diseases. Methods Differentially expressed genes (DEGs) for COVID-19 and NAFLD were extracted from the GSE147507 and GSE89632 datasets, and common DEGs were identified using the Venn diagram. Subsequently, we constructed a protein–protein interaction (PPI) network based on the common DEGs and extracted hub genes. Then, we performed gene ontology (GO) and pathway analysis of common DEGs. In addition, transcription factors (TFs) and miRNAs regulatory networks were constructed, and drug candidates were identified. Results We identified a total of 62 common DEGs for COVID-19 and NAFLD. The 10 hub genes extracted based on the PPI network were IL6, IL1B, PTGS2, JUN, FOS, ATF3, SOCS3, CSF3, NFKB2, and HBEGF. In addition, we also constructed TFs–DEGs, miRNAs–DEGs, and protein–drug interaction networks, demonstrating the complex regulatory relationships of common DEGs. Conclusion We successfully extracted 10 hub genes that could be used as novel therapeutic targets for COVID-19 and NAFLD. In addition, based on common DEGs, we propose some potential drugs that may benefit patients with COVID-19 and NAFLD.

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“…et al identified preferred drug candidates from their in-house database of approved drugs found via anti-SARS-CoV-2 activity screen and the analysis of the inhibitory profiles of the human ether-à-go-go-related gene (hERG), phospholipidosis and many cytotoxicity screens. 10 In addition, the hERG liability of anti-SARS-CoV-2 drugs currently enrolled in clinical trials was also highlighted.…”

Section: Repurposing Drugs As Anti-infective Therapiesmentioning

confidence: 99%

Drug repurposing: An effective strategy to accelerate contemporary drug discovery

Zhan

Ouyang

2022

Drug Discovery Today

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Repurposing drugs as COVID-19 therapies: A toxicity evaluation

Cited by 16 publications

References 63 publications

Erythromycin, Retapamulin, Pyridoxine, Folic acid and Ivermectin dose dependently inhibit cytopathic effect, Papain-like Protease and M^PROof SARS-CoV-2

Erythromycin, Retapamulin, Pyridoxine, Folic acid and Ivermectin dose dependently inhibit cytopathic effect, Papain-like Protease and M^PROof SARS-CoV-2

Systems biology approach reveals a common molecular basis for COVID-19 and non-alcoholic fatty liver disease (NAFLD)

Drug repurposing: An effective strategy to accelerate contemporary drug discovery

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Repurposing drugs as COVID-19 therapies: A toxicity evaluation

Cited by 16 publications

References 63 publications

Erythromycin, Retapamulin, Pyridoxine, Folic acid and Ivermectin dose dependently inhibit cytopathic effect, Papain-like Protease and MPROof SARS-CoV-2

Erythromycin, Retapamulin, Pyridoxine, Folic acid and Ivermectin dose dependently inhibit cytopathic effect, Papain-like Protease and MPROof SARS-CoV-2

Systems biology approach reveals a common molecular basis for COVID-19 and non-alcoholic fatty liver disease (NAFLD)

Drug repurposing: An effective strategy to accelerate contemporary drug discovery

Contact Info

Product

Resources

About

Erythromycin, Retapamulin, Pyridoxine, Folic acid and Ivermectin dose dependently inhibit cytopathic effect, Papain-like Protease and M^PROof SARS-CoV-2

Erythromycin, Retapamulin, Pyridoxine, Folic acid and Ivermectin dose dependently inhibit cytopathic effect, Papain-like Protease and M^PROof SARS-CoV-2