Repurposing Estrogen Receptor Antagonists for the Treatment of Infectious Disease

Montoya, Marhiah C.; Krysan, Damian J.

doi:10.1128/mbio.02272-18

Cited by 61 publications

(49 citation statements)

References 76 publications

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“…In addition, BSAAs showed activity against a wide range of other medically important human pathogens, including fungi, protozoa and parasites (Table S1) (Montoya and Krysan, 2018), pointing out that some pathogens utilize common mechanisms to infect hosts. Moreover, structure-activity relationship analysis of BSAAs suggest that some agents, such as doxycycline, artesunate, omeprazole, nitazoxanide, suramin, azithromycin, minocycline and chloroquine, could have novel antibacterial, antiprotozoal, antifungal or anthelmintic activities (Figure 4).…”

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

“…In addition, BSAAs showed activity against a wide range of other medically important human pathogens, including fungi, protozoa and parasites (Table S1) (115), pointing out that some pathogens utilize common mechanisms to infect hosts. Moreover, structure-activity relationship analysis of BSAAs suggest that some agents, such as doxycycline, artesunate, omeprazole, nitazoxanide, suramin, azithromycin, minocycline and chloroquine, could have novel antibacterial, antiprotozoal, antifungal or anthelmintic activities (Fig.…”

Section: Other Activities Of Bsaasmentioning

confidence: 99%

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

Andersen¹,

Ianevski²,

Lysvand³

et al. 2019

Preprint

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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) could provide additional protection of general population from emerging and re-emerging viral diseases reinforcing the arsenal of available antiviral options. Here, we reviewed development process of BSAAs and summarized the information on 119 safe-in-man agents in freely accessible database (https://drugvirus.info/). The number of BSAAs will be increased, their developmental status will be updated, spectrum of their indications will be expanded, as well as BSAA combinations will be approved pending the results of further pre-clinical and clinical studies.

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“…20 For repurpose of TAM, antifungal action is another potential activity that can add to its therapeutic ability of breast cancer. 21 Wiseman et al gave the first indicator for antifungal activity of TAM against Saccharomyces cerevisiae. 22 A few years later, many studies demonstrated that TAM has such activity against other types of fungi.…”

Section: Tamoxifen As An Anti-fungal Drugmentioning

confidence: 99%

Tamoxifen: From Anti-cancer to Antifungal Drug

2019

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Tamoxifen (TAM) is an important drug for treatment of breast cancer. It is most effective against estrogen receptor-positive and negative breast cancer. Protective adjuvant is another applied of TAM for women at risk of development of breast cancer. Anti-cancer activity of TAM can take various pathways of action. Antagonistic with estrogen receptor and oxidation reaction are the most proposed mechanism of action of TAM in cancer cells. Recently, many studies focused on the potential antimicrobial action of TAM. Fungi are demonstrated to affect by TAM through various mechanism of action. Yeasts, especially Candida albicans, are the most common type of fungi used to test the antifungal action of TAM. Inhibitory action on some components of the calcium-calcineurin pathway in fungal cells is most acceptable mechanism of TAM action. TAM can also play a synergistic role to increase the antifungal activity of other standard agents. This review will discuss the most recent information about antifungal action of TAM.

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Repurposing Estrogen Receptor Antagonists for the Treatment of Infectious Disease

Cited by 61 publications

References 76 publications

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

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

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

Tamoxifen: From Anti-cancer to Antifungal Drug

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