Repurposing of Kinase Inhibitors as Broad-Spectrum Antiviral Drugs

Schor, Stanford; Einav, Shirit

doi:10.1089/dna.2017.4033

Cited by 78 publications

(68 citation statements)

References 71 publications

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“…Anti-malaria quinolones (chloroquine and hydroxychloroquine) inhibit acidification of endosomes, which is an essential process for uncoating of ssRNA viruses (Al-Bari, 2017). Anticancer kinase inhibitors dasatinib, imatinib, gefitinib, nilotinib, erlotinib and sunitinib impair intracellular viral trafficking and exert BSA effects (Bekerman et al, 2017;Schor and Einav, 2018). The anti-Duchenne muscular dystrophy agent, alisporivir, targets cellular cyclophilin and inhibits the folding of HCV, HIV, MERS-and SARS-CoV proteins, and, therefore, prevents formation of infectious virus particles (Boldescu et al, 2017;de Wilde et al, 2017;Soriano et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Novel activities of safe-in-human broad-spectrum antiviral agents

et al. 2018

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According to the WHO, there is an urgent need for better control of viral diseases. Re-positioning existing safe-in-human antiviral agents from one viral disease to another could play a pivotal role in this process. Here, we reviewed all approved, investigational and experimental antiviral agents, which are safe in man, and identified 59 compounds that target at least three viral diseases. We tested 55 of these compounds against eight different RNA and DNA viruses. We found novel activities for dalbavancin against echovirus 1, ezetimibe against human immunodeficiency virus 1 and Zika virus, as well as azacitidine, cyclosporine, minocycline, oritavancin and ritonavir against Rift valley fever virus. Thus, the spectrum of antiviral activities of existing antiviral agents could be expanded towards other viral diseases.

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Section: Introductionmentioning

confidence: 99%

Novel activities of safe-in-human broad-spectrum antiviral agents

et al. 2018

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“…Mounting evidence have shown that viruses hijack a variety of human kinases throughout the entire viral life cycle to facilitate their replications, and some kinases are broadly required. [109][110][111] Therefore, it can be anticipated that the inhibition of such kinases would lead to the disruption of a broad spectrum of viral replications. Since tremendous kinase inhibitors have been approved in clinic for treating cancer and inflammatory diseases, and more are under development in the pipelines, increasing efforts have been devoted to repurposing approved kinase inhibitors as broad-spectrum antiviral agents.…”

Section: Kinasesmentioning

confidence: 99%

“…Many other kinases are also involved and play essential roles in different life cycle of various viruses, and their corresponding kinase inhibitors show broad-spectrum antiviral activities against a wide range of viruses both in vitro and in vivo. [109][110][111] Since host kinase is not under the genetic control of virus, kinase inhibitors for antiviral treatment have much higher genetic barrier to resistance. For example, DENV developed resistance against the viral NS4B inhibitor SDM25N after eight passages, yet it remained sensitive to the treatment of 49 and 50 under the same conditions.…”

Section: Kinasesmentioning

confidence: 99%

Medicinal chemistry strategies toward host targeting antiviral agents

2020

Medicinal Research Reviews

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Direct-acting antiviral agents (DAAs) represent a class of drugs targeting viral proteins and have been demonstrated to be very successful in combating viral infections in clinic. However, DAAs suffer from several inherent limitations, including narrow-spectrum antiviral profiles and liability to drug resistance, and hence there are still unmet needs in the treatment of viral infections. In comparison, host targeting antivirals (HTAs) target host factors for antiviral treatment. Since host proteins are probably broadly required for various viral infections, HTAs are not only perceived, but also demonstrated to exhibit broad-spectrum antiviral activities. In addition, host proteins are not under the genetic control of viral genome, and hence HTAs possess much higher genetic barrier to drug resistance as compared with DAAs. In recent years, much progress has been made to the development of HTAs with the approval of chemokine receptor type 5 antagonist maraviroc for human immunodeficiency virus treatment and more in the pipeline for other viral infections. In this review, we summarize various host proteins as antiviral targets from a medicinal chemistry prospective. Challenges and issues associated with HTAs are also discussed. K E Y W O R D S broad-spectrum antivirals, direct-acting antiviral agents, drug resistance, host targeting antiviral agents

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“…Due to all these reasons, we urgently need new, efficient, broadspectrum antivirals (Howard and Fletcher, 2012;Schor and Einav, 2018). The traditional strategy in drug development of one virus one drug, based in the development of molecules that specifically target a viral protein, has been very successful for certain viruses like HIV or hepatitis C virus (HCV) (Barre-Sinoussi et al, 2013;Li and De Clercq, 2017).…”

Section: Introductionmentioning

confidence: 99%

Drug repurposing for new, efficient, broad spectrum antivirals

2019

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Emerging viruses are a major threat to human health. Recent outbreaks have emphasized the urgent need for new antiviral treatments. For several pathogenic viruses, considerable efforts have focused on vaccine development. However, during epidemics infected individuals need to be treated urgently. High-throughput screening of clinically tested compounds provides a rapid means to identify undiscovered, antiviral functions for wellcharacterized therapeutics. Repurposed drugs can bypass part of the early cost and time needed for validation and authorization. In this review we describe recent efforts to find broad spectrum antivirals through drug repurposing. We have chosen several candidates and propose strategies to understand their mechanism of action and to determine how resistance to antivirals develops in infected cells.

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Repurposing of Kinase Inhibitors as Broad-Spectrum Antiviral Drugs

Cited by 78 publications

References 71 publications

Novel activities of safe-in-human broad-spectrum antiviral agents

Novel activities of safe-in-human broad-spectrum antiviral agents

Medicinal chemistry strategies toward host targeting antiviral agents

Drug repurposing for new, efficient, broad spectrum antivirals

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