Expanding the activity spectrum of antiviral agents

Ianevski, Aleksandr; Andersen, Petter I.; Merits, Andres; Bjørås, Magnar; Kainov, Denis E.

doi:10.1016/j.drudis.2019.04.006

Cited by 43 publications

(54 citation statements)

References 48 publications

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“…Through previous literature review, we identified 136 safe-in-man BSAAs and made a database to bring this information into the public domain (https://drugvirus.info/). Recently, we have expanded on the spectrum of activities for some of these BSAAs (Andersen et al, 2020a;Andersen et al, 2019;Bosl et al, 2019b;Ianevski et al, 2019a;Ianevski et al, 2018). Some of these agents could be repositioned for treatment of SARS-CoV-2 infection.…”

Section: Repurposing Safe-in-man Bsaasmentioning

confidence: 99%

Potential antiviral options against SARS-CoV-2 infection

Ianevski

Yao

Fenstad

et al. 2020

Preprint

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As of May 2020, the number of people infected with SARS-CoV-2 continues to skyrocket, with more than 4,5 million cases worldwide. Both the World Health Organization (WHO) and United Nations (UN) has highlighted the need for better control of SARS-CoV-2 infections. Developing novel virus-specific vaccines, monoclonal antibodies and antiviral drugs against SARS-CoV-2 can be time-consuming and costly. Convalescent plasma and safe-in-man broad-spectrum antivirals (BSAAs) are readily available treatment options. Here we developed a neutralization assay using SARS-CoV-2 virus and monkey Vero-E6 cells. We identified most potent sera from recovered patients for treatment of SARS-CoV-2-infected patients. We also screened 136 safe-in-man broad-spectrum antivirals against SARS-CoV-2 infection in Vero-E6 cells and identified antiviral activity of nelfinavir, salinomycin, amodiaquine, obatoclax, emetine and homoharringtonine. We found that combinations of virus-directed drug nelfinavir with host-directed drugs, such as salinomycin, amodiaquine, obatoclax, emetine and homoharringtonine exhibit synergistic effect against SARS-CoV-2 in vitro. Finally, we developed a website to disseminate the knowledge on available and emerging treatments of COVID-19.

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Section: Repurposing Safe-in-man Bsaasmentioning

confidence: 99%

Potential antiviral options against SARS-CoV-2 infection

Ianevski

Yao

Fenstad

et al. 2020

Preprint

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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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“…Previously, there has been a focus on "one drug, one virus" dogma, which relied on targeting virus-specific factors. A counterpoint to this is "one drug, multiple viruses" paradigm, which came with the discovery of broad-spectrum antiviral agents (BSAAs), small-molecules that inhibit a wide range of human viruses (Bekerman and Einav, 2015;de Clercq and Montgomery, 1983;Debing et al, 2015;Ianevski et al, 2019;Rada and Dragun, 1977;Sidwell et al, 1972). This paradigm was based on the observation that different viruses utilize similar pathways and host factors to replicate inside a cell (Bosl et al, 2019).…”

mentioning

confidence: 99%

Discovery and development of safe-in-man broad-spectrum antiviral agents

Andersen

Ianevski

Lysvand

et al. 2020

International Journal of Infectious Diseases

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# Contributed equally J o u r n a l P r e -p r o o f Highlights  We reviewed discovery and development process of broad-spectrum antiviral agents.  We summarized the information on 119 safe-in-man agents in freely accessible database.  Further studies will increase the number of broad-spectrum antivirals, expand spectrum of their indications, and identify drug combinations for treatment of emerging and re-emerging viral infections. Abstract: Viral diseases are one of the leading causes of morbidity and mortality in the world. Virus-specific vaccines and antiviral drugs are the most powerful tools to combat viral diseases. However, broad-spectrum antiviral agents (BSAAs, i.e. compounds targeting viruses belonging to two or more viral families) could provide additional protection of general population from emerging and reemerging viral diseases reinforcing the arsenal of available antiviral options. Here, we reviewed discovery and development of BSAAs and summarized the information on 119 safe-in-man agents in freely accessible database (https://drugvirus.info/). Future and ongoing pre-clinical and clinical studies will increase the number of BSAAs, expand spectrum of their indications, and identify drug combinations for treatment of emerging and re-emerging viral infections as well as co-infections. J o u r n a l P r e -p r o o f 2015). Antiviral drugs and vaccines are used to fight viral infections in human (De Clercq and Li, 2016; Marston et al., 2014). Previously, there has been a focus on "one drug, one virus" dogma, which relied on targeting virus-specific factors. A counterpoint to this is "one drug, multiple viruses" paradigm, which came with the discovery of broad-spectrum antiviral agents (BSAAs), small-molecules that inhibit a wide range of human viruses (Bekerman and Einav, 2015; de Clercq and Montgomery, 1983; Debing et al., 2015; Ianevski et al., 2019; Rada and Dragun, 1977; Sidwell et al., 1972). This paradigm was based on the observation that different viruses utilize similar pathways and host factors to replicate inside a cell (Bosl et al., 2019). Although the concept of BSAAs has been around for almost 50 years, the field received a new impetus with recent outbreaks of Ebola, Zika, Dengue, influenza and other viral infections, the discovery of novel host-directed agents as well as development of drug repositioning methodology. Drug repurposing, also called repositioning, redirecting, reprofiling, is a strategy for generating additional value from an existing drug by targeting disease other than that for which it was originally intended (Nishimura and Hara, 2018; Pushpakom et al., 2019). This has significant advantages over new drug discovery since chemical synthesis steps, manufacturing processes, reliable safety, and pharmacokinetic properties in pre-clinical (animal model) and early clinical developmental phases (phase 0, I and IIa) are already available (Figure 1). Therefore, repositioning of launched or even failed drugs to viral diseases provides unique translational opportunities, includi...

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Expanding the activity spectrum of antiviral agents

Cited by 43 publications

References 48 publications

Potential antiviral options against SARS-CoV-2 infection

Potential antiviral options against SARS-CoV-2 infection

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

Discovery and development of safe-in-man broad-spectrum antiviral agents

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