Gemcitabine and Nucleos(t)ide Synthesis Inhibitors Are Broad-Spectrum Antiviral Drugs that Activate Innate Immunity

Shin, Hye Jin; Kim, Chonsaeng; Cho, Sungchan

doi:10.3390/v10040211

Cited by 28 publications

(28 citation statements)

References 45 publications

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“…Gemcitabine ( 7 , Figure 3 ) is a deoxycytidine analog with a broad-spectrum antiviral activity that inhibits SARS-CoV-1 and MERS-CoV [ 120 ]. Gemcitabine potential as an anti-COVID-19 drug was recently investigated in cell culture [ 121 ].…”

Section: Nucleoside Analogs As Anti-hcov Drugsmentioning

confidence: 99%

Nucleoside Analogs and Nucleoside Precursors as Drugs in the Fight against SARS-CoV-2 and Other Coronaviruses

et al. 2021

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Coronaviruses (CoVs) are positive-sense RNA enveloped viruses, members of the family Coronaviridae, that cause infections in a broad range of mammals including humans. Several CoV species lead to mild upper respiratory infections typically associated with common colds. However, three human CoV (HCoV) species: Severe Acute Respiratory Syndrome (SARS)-CoV-1, Middle East Respiratory Syndrome (MERS)-CoV, and SARS-CoV-2, are responsible for severe respiratory diseases at the origin of two recent epidemics (SARS and MERS), and of the current COronaVIrus Disease 19 (COVID-19), respectively. The easily transmissible SARS-CoV-2, emerging at the end of 2019 in China, spread rapidly worldwide, leading the World Health Organization (WHO) to declare COVID-19 a pandemic. While the world waits for mass vaccination, there is an urgent need for effective drugs as short-term weapons to combat the SARS-CoV-2 infection. In this context, the drug repurposing approach is a strategy able to guarantee positive results rapidly. In this regard, it is well known that several nucleoside-mimicking analogs and nucleoside precursors may inhibit the growth of viruses providing effective therapies for several viral diseases, including HCoV infections. Therefore, this review will focus on synthetic nucleosides and nucleoside precursors active against different HCoV species, paying great attention to SARS-CoV-2. This work covers progress made in anti-CoV therapy with nucleoside derivatives and provides insight into their main mechanisms of action.

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Section: Nucleoside Analogs As Anti-hcov Drugsmentioning

confidence: 99%

Nucleoside Analogs and Nucleoside Precursors as Drugs in the Fight against SARS-CoV-2 and Other Coronaviruses

et al. 2021

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“…Recently, experimental data on the antiviral activity of gemcitabine have been widely reported (Shin et al, 2018;Ianevski et al, 2019). The broad range of viruses against which gemcitabine has shown activity includes HIV-1 (Rawson et al, 2013;Clouser et al, 2010Clouser et al, , 2012, murine leukaemia virus (MuLV) (Clouser et al, 2012), HIV-2 (Beach et al, 2014), ZIKV (Kuivanen et al, 2017), enteroviruses such as poliovirus (Kang et al, 2015;Zhang et al, 2017), rhinoviruses (Song et al, 2017), HCV (Beran et al, 2012), coronaviruses (Dyall et al, 2014), Sindbis virus (SINV), HSV-1 and FLUAV (Denisova et al, 2012).…”

Section: Nucleoside Antimetabolites -Approved Antineoplastic Drugs Wimentioning

confidence: 99%

Selected nucleos(t)ide-based prescribed drugs and their multi-target activity

Pastuch-Gawołek

Gillner

Król

et al. 2019

European Journal of Pharmacology

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A B S T R A C T Nucleos(t)ide analogues play pivotal roles as antiviral, cytotoxic or immunosuppressive agents. Here, we review recent reports of nucleoside analogues that exhibit broad-spectrum activity towards multiple life-threatening RNA and DNA viruses. We also present a discussion about nucleoside antimetabolites-approved antineoplastic agents-that have recently been shown to have antiviral and/or antibacterial activity. The approved drugs and drug combinations, as well as recently identified candidates for investigation and/or experimentation, are discussed. Several examples of repurposed drugs that have already been approved for use are presented. This strategy can be crucial for the first-line treatment of acute infections or coinfections and for the management of drug-resistant strains.T against viral infections of great medical importance (e.g., herpes simplex virus (HSV), varicella zoster virus (VZV), human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV)) and/or that are known antineoplastic agents used to treat cancer. Approved nucleos(t)ide-based drugs with multi-target activity and compounds being tested in clinical trials or evaluated in preclinical assays are listed in Table 1. In this paper, the term "approval date" means the date on which the drug was approved by the US Food and Drug Administration (FDA) unless otherwise stated. G. Pastuch-Gawołek, et al. Multi-target nucleos(t)ide-based drugs in the treatment and prophylaxis of HIV, HBV and HCV infections

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“…Gemcitabine has been explored in combination therapies with HAdV-based vectors in a number of studies for treatment of cancer ( Nattress and Hallden, 2018 ), but not as an HAdV-directed antiviral therapeutic. However, it does show broad spectrum antiviral activity against many RNA viruses, such as Middle East respiratory syndrome coronavirus, severe acute respiratory syndrome coronavirus, Zika virus, HCV, poliovirus, influenza A virus, HIV, and enteroviruses ( Shin et al, 2018 ), as well as the dsDNA-containing Herpes simplex virus type I ( Denisova et al, 2012 ). Other nucleoside analogs have shown efficacy against HAdV, including cidofovir, ganciclovir and ribavirin ( Keyes et al, 2016 ; Lenaerts et al, 2008 ; Ronchi et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of human adenovirus replication inhibitors from a library of small molecules targeting cellular epigenetic regulators

Saha

Parks

2021

Virology

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Human adenovirus (HAdV) can cause severe disease in certain at-risk populations such as newborns, the elderly and those with compromised immune systems. Unfortunately, no FDA-approved anti-HAdV drug is currently available for treatment. Within the nucleus of infected cells, the HAdV genome associates with histones and forms a chromatin-like structure during early infection, and viral gene expression appears regulated by cellular epigenetic processes. Thus, one potential therapeutic strategy to combat HAdV disease may be to target the cellular proteins involved in modifying the viral nucleoprotein structure and facilitating HAdV gene expression and replication. We have screened a panel of small molecules that modulate the activity of epigenetic regulatory proteins for compounds affecting HAdV gene expression. Several of the compounds, specifically chaetocin, gemcitabine and lestaurtinib, reduced HAdV recovery by 100- to 1000-fold, while showing limited effect on cell health, suggesting that these compounds may indeed be promising as anti-HAdV therapeutics.

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Gemcitabine and Nucleos(t)ide Synthesis Inhibitors Are Broad-Spectrum Antiviral Drugs that Activate Innate Immunity

Cited by 28 publications

References 45 publications

Nucleoside Analogs and Nucleoside Precursors as Drugs in the Fight against SARS-CoV-2 and Other Coronaviruses

Nucleoside Analogs and Nucleoside Precursors as Drugs in the Fight against SARS-CoV-2 and Other Coronaviruses

Selected nucleos(t)ide-based prescribed drugs and their multi-target activity

Identification of human adenovirus replication inhibitors from a library of small molecules targeting cellular epigenetic regulators

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