Toxicology studies of primycin-sulphate using a three-dimensional (3D) in vitro human liver aggregate model

Pénzes, Ágota; Abdelwahab, Elhusseiny Mohamed Mahmud; Rapp, Judit; Péteri, Zsanett A.; Bovari-Biri, Judit; Fekete, Csaba; Miskei, György; Kvell, Krisztián; Pongrácz, Judit E.

doi:10.1016/j.toxlet.2017.09.005

Cited by 5 publications

(5 citation statements)

References 45 publications

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“…The binding of nystatin to cholesterol in cell membranes causes changes in plasma membrane fluidity and cell permeability therefore decreases infectivity of lipid-enveloped viruses. The drug-sterol interaction is a well-known phenomenon that has already been demonstrated in our earlier studies on the macrolide antibiotic primycin (84–90) where the membrane disorganization was due to the ergosterol-primycin bound stabilized by hydrogen bounds (87).…”

Section: Discussionmentioning

confidence: 70%

Repurposed nystatin to inhibit SARS-CoV-2 and mutants in the GI tract

Virág

Seffer

Pénzes-Hűvös

et al. 2021

Preprint

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The SARS-CoV-2 infections are considered as respiratory system diseases, mostly. In COVID-19, it might also be the infection of gastrointestinal (GI) tract too, especially at patients in severe clinical condition. SARS-CoV-2 can destroy the intestinal barrier, capable to spread into internal organs via blood and/or lymphatic circulation, and to cause serious damage there. Infected GI tract of COVID-19 patients is ideal environment for the coronavirus infection, replication and as virus reservoir might be the major source of pandemic reinfections, too. The process of virus budding is dependent on the host cell lipid rafts containing membrane-sterols, mainly cholesterol. The viral envelope may be challenged by polyene antibiotics, such as nystatin, which has strong affinity to sterols. Nystatin may block the establishment of the virus-host cell connection, too. In this study, the nystatin was investigated, as antiviral agent to SARS-CoV-2. We demonstrated by tests in Vero E6 cell based cytopathic assay, nystatin blocked the replication of SARS-CoV-2 in concentration 62.5 μg/ml (IC50) at Wuhan and British mutant strains. No efficient SARS-CoV-2 antiviral agent is known so far to alleviate pandemic, to disinfect GI tract, where vaccines might have limited effect, only. Nystatin might be the first one with emergency use authorization, either, as a safe and efficient non-systemic antiviral drug, with well-established use, since decades.

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Section: Discussionmentioning

confidence: 70%

Repurposed nystatin to inhibit SARS-CoV-2 and mutants in the GI tract

Virág

Seffer

Pénzes-Hűvös

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…In this way, the total dilution may be around 5-6 liter in GIT juice daily [66], thus the determined effective antiviral concentration is only about the half of the maximum allowed daily concentration of nystatin. This means there is no reason to change the well-established dosage regimen in a potential SARS-CoV-2 GIT disinfection therapy either [88][89][90].…”

Section: Discussionmentioning

confidence: 99%

"Repurposed Nystatin to Inhibit SARS-Cov-2 and Mutants in the GI Tract"

Virág

2021

BJSTR

View full text Add to dashboard Cite

The SARS-CoV-2 infections are considered as respiratory system diseases, mostly. In COVID-19, it might also be the infection of gastrointestinal (GI) tract too, especially at patients in severe clinical condition. SARS-CoV-2 can destroy the intestinal barrier, capable to spread into internal organs via blood and/or lymphatic circulation, and to cause serious damage there. Infected GI tract of COVID-19 patients is ideal environment for the coronavirus infection, replication and as virus reservoir might be the major source of pandemic reinfections, too. The process of virus budding is dependent on the host cell lipid rafts containing membrane-sterols, mainly cholesterol. The viral envelope may be challenged by polyene antibiotics, such as nystatin, which has strong affinity to sterols. Nystatin may block the establishment of the virus-host cell connection, too. In this study, the nystatin was investigated, as antiviral agent to SARS-CoV-2. We demonstrated by tests in Vero E6 cell based cytopathic assay, nystatin blocked the replication of SARS-CoV-2 in concentration 62.5 µg/ml (IC50) at Wuhan and British mutant strains. No efficient SARS-CoV-2 antiviral agent is known so far to alleviate pandemic, to disinfect GI tract, where vaccines might have limited effect, only. Nystatin might be the first one with emergency use authorization, either, as a safe and efficient non-systemic antiviral drug, with well-established use since decades.Diarrhea has been listed as a symptom of COVID-19 in the guideline

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“…They used V-shaped plates to form aggregates within 24 h and observed that the level of primycin-sulfate induced cell death was lower than in 2D cultures. Furthermore, the non-toxic level of primycin-sulfate treatment resulted in an increased expression of IL-11 and IL-24[ 57 ]. Bell et al .…”

Section: Spheroidsmentioning

confidence: 99%

Toward better drug development: Three-dimensional bioprinting in toxicological research

Szűcs¹,

Fekete²,

Guba³

et al. 2023

IJB

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The importance of three-dimensional (3D) models in pharmacological tests and personalized therapies is significant. These models allow us to gain insight into the cell response during drug absorption, distribution, metabolism, and elimination in an organ-like system and are suitable for toxicological testing. In personalized and regenerative medicine, the precise characterization of artificial tissues or drug metabolism processes is more than crucial to gain the safest and the most effective treatment for the patients. Using these 3D cell cultures derived directly from patient, such as spheroids, organoids, and bioprinted structures, allows for testing drugs before administration to the patient. These methods allow us to select the most appropriate drug for the patient. Moreover, they provide chance for better recovery of patients, since time is not wasted during therapy switching. These models could be used in applied and basic research as well, because their response to treatments is quite similar to that of the native tissue. Furthermore, they may replace animal models in the future because these methods are cheaper and can avoid interspecies differences. This review puts a spotlight on this dynamically evolving area and its application in toxicological testing.

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Toxicology studies of primycin-sulphate using a three-dimensional (3D) in vitro human liver aggregate model

Cited by 5 publications

References 45 publications

Repurposed nystatin to inhibit SARS-CoV-2 and mutants in the GI tract

Repurposed nystatin to inhibit SARS-CoV-2 and mutants in the GI tract

"Repurposed Nystatin to Inhibit SARS-Cov-2 and Mutants in the GI Tract"

Toward better drug development: Three-dimensional bioprinting in toxicological research

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