Niclosamide inhibits lytic replication of Epstein-Barr virus by disrupting mTOR activation

Huang, Lu; Yang, Mengtian; Yuan, Yan; Li, Xiaojuan; Kuang, Ersheng

doi:10.1016/j.antiviral.2016.12.002

Cited by 35 publications

(28 citation statements)

References 58 publications

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“…Amodiaquine is an anti-malaria drug, which also possesses antiviral activities against DENV, HCV, RRV, SINV, WNV, EFV, EBOV, LASV, RABV, VZV, and HSV-1 in immortalized cell cultures (Boonyasuppayakorn et al, 2014;Hulseberg et al, 2019;Mazzon et al, 2019). Niclosamide is an orally bioavailable anthelmintic drug, which inhibits the broadest range of viruses in vitro and, in some cases, in vivo (Cairns et al, 2018;Fang et al, 2013;Huang et al, 2017;Hulseberg et al, 2019;Jurgeit et al, 2012;Kao et al, 2018;Mazzon et al, 2019;Stachulski et al, 2011;Wang et al, 2016;Wu et al, 2004). These safe-in-man BSAAs represent promising drug candidates.…”

Section: J O U R N a L P R E -P R O O Fmentioning

confidence: 99%

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

Andersen

Ianevski

Lysvand

et al. 2020

International Journal of Infectious Diseases

198

108

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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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Section: J O U R N a L P R E -P R O O Fmentioning

confidence: 99%

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

Andersen

Ianevski

Lysvand

et al. 2020

International Journal of Infectious Diseases

198

108

View full text Add to dashboard Cite

show abstract

“…Niclosamide is an orally bioavailable anthelmintic drug and potential antineoplastic agent. In addition, it inhibits the broadest range of viruses, including HSV-2, in vitro and, in some cases, in vivo [28][29][30][31][32][33][34][35][36][37]. It was shown that niclosamide induces endosomal neutralization and prevents virus entry into host cells.…”

Section: Discussionmentioning

confidence: 99%

Novel Antiviral Activities of Obatoclax, Emetine, Niclosamide, Brequinar, and Homoharringtonine

Andersen¹,

Krpina²,

Ianevski³

et al. 2019

Preprint

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Viruses are the major causes of acute and chronic infectious diseases in the world. According to the World Health Organization, there is an urgent need for better control of viral diseases. Re-purposing existing antiviral agents from one viral disease to another could play a pivotal role in this process. Here we identified novel activities of obatoclax and emetine against herpes simplex virus type 2 (HSV-2), human immunodeficiency virus 1 (HIV-1), echovirus 1 (EV1), human metapneumovirus (HMPV) and Rift Valley fever virus (RVFV) in cell cultures. Moreover, we demonstrated novel activities of emetine against influenza A virus (FluAV), niclosamide against HSV-2, brequinar against HIV-1, and homoharringtonine against EV1. Our findings may expand the spectrum of indications of these safe-in-man agents and reinforce the arsenal of available antiviral therapeutics pending the results of further in vivo tests.

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Section: Evaluation Of Bsaas In Human Primary Cell Culture and Co-culmentioning

confidence: 99%

Discovery and Development of Safe-in-Man Broad-Spectrum Antiviral Agents

Andersen¹,

Ianevski²,

Lysvand³

et al. 2020

Preprint

View full text Add to dashboard Cite

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 re-emerging viral diseases reinforcing the arsenal of available antiviral options. Here, we reviewed discovery and development of BSAAs and summarized the information on 120 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.

show abstract

Niclosamide inhibits lytic replication of Epstein-Barr virus by disrupting mTOR activation

Cited by 35 publications

References 58 publications

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

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

Novel Antiviral Activities of Obatoclax, Emetine, Niclosamide, Brequinar, and Homoharringtonine

Discovery and Development of Safe-in-Man Broad-Spectrum Antiviral Agents

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