Cysteamine with In Vitro Antiviral Activity and Immunomodulatory Effects Has the Potential to Be a Repurposing Drug Candidate for COVID-19 Therapy

Alonzi, Tonino; Aiello, Alessandra; Petrone, Linda; Fard, Saeid Najafi; D’Eletto, Manuela; Falasca, Laura; Nardacci, Roberta; Rossin, Federica; Delogu, Giovanni; Castilletti, Concetta; Capobianchi, Maria Rosaria; Ippolito, Giuseppe; Piacentini, Mauro; Goletti, Delia

doi:10.3390/cells11010052

Cited by 15 publications

(20 citation statements)

References 46 publications

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“…Recently, we have reported that cysteamine and its oxidation product cystamine exert a direct antiviral action against the Wild type SARS-CoV-2 strain isolated at INMI L. Spallanzani IRCCS [ 15 ]. We then tested whether cysteamine had an impact on the life cycle of recent SARS-CoV-2 VOC and, therefore, we performed the viral-induced cytopathic effects (CPE) inhibition assay in Vero E6 cells.…”

Section: Resultsmentioning

confidence: 99%

“…To understand whether cysteamine directly affects the life cycle of the different SARS-CoV-2 variants, we measured the amount of the infectious viral particles released in the culture medium of Vero E6 cells treated with either cysteamine or with the drug-vehicle (H 2 O) at 72 h.p.i. We evaluated viral production by back-titrating the culture supernatants of the infected cells using a limiting dilution assay, as we recently described [ 15 ].…”

Section: Resultsmentioning

confidence: 99%

“…Repurposing drugs can be a valid pragmatic approach to treat diseases as COVID-19 [ 10 – 14 ]. We have recently shown that in vitro cysteamine, an approved drug for nephropathic cystinosis, (i) reduces SARS-CoV-2-induced cytopathic effects (CPE) in Vero E6, (ii) decreases the viral production in Vero E6 and Calu-3 cells and (iii) displays anti-inflammatory effects in cells from COVID-19 patients [ 15 ]. Cysteamine, 2-aminoethanethiol, is a rather simple aliphatic compound, which became, since the FDA’s approval in 1994, the gold standard of care for the treatment of nephropathic cystinosis [ 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

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Cysteamine exerts in vitro antiviral activity against the SARS-CoV-2 Delta and Omicron variants

et al. 2022

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The novel SARS-CoV-2 variants of concern (VOC) represent a considerable global alarm because their mutations are known to affect transmissibility and cause immune escape. While preventing severe disease and deaths, the available vaccines do not avoid infection; therefore, COVID-19 disease management still requires effective therapies. We have recently reported that the aminothiol cysteamine, a drug already applied to humans, exerts direct antiviral activity against SARS-CoV-2 and has in vitro immunomodulatory effect. To evaluate whether this compound exerts antiviral effects also against SARS-CoV-2 variants, we performed different infected cell-based assays using Wild type, Delta, or Omicron VOC. We found that cysteamine significantly reduces the cytopathic effect induced by SARS-CoV-2 Wild type strain and Delta variant in Vero E6 cells. On the other hand, cysteamine had no effects on the survival of cells infected with the Omicron variant, due to the lack of cytotoxicity on Vero E6 cells, at least when infected at MOI = 0.001 for 72 h. Moreover, cysteamine significantly reduced the production of Wild type, Delta, and Omicron variants as measured by the virus released in the culture media (Vero E6 and Calu-3 cells) and by transmission electron microscopy analysis (Vero E6 cells). Notably, cysteamine is more effective in inhibiting the Omicron rather than Delta or Wild type viruses, with an 80% inhibition of Omicron production compared to 40% of Wild type and Delta variant. Overall, our findings demonstrate that cysteamine exerts direct antiviral actions against SARS-CoV-2 Delta and Omicron variants, in addition to the Wild type virus. Our data further demonstrate that cysteamine is a good candidate as repurposing drug for the treatment of SARS-CoV-2 infection for the present and, likely, the future VOC and, therefore, it would be important to investigate its clinical relevance in randomized clinical trials.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cysteamine exerts in vitro antiviral activity against the SARS-CoV-2 Delta and Omicron variants

et al. 2022

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“…Cysteamine and cystamine significantly decreased the viral production in Vero E6 and Calu-3 cells, and their antiviral action did not depend on the treatment time with respect to SARS-CoV-2 infection. Additionally, they showed an anti-inflammatory effect by lowering the SARS-CoV-2 specific IFN-γ production in vitro, using blood samples from COVID-19 patients [ 146 ].…”

Section: Recent Preclinical Studiesmentioning

confidence: 99%

COVID-19 at a Glance: An Up-to-Date Overview on Variants, Drug Design and Therapies

Iacopetta

Ceramella

Catalano

et al. 2022

Viruses

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Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a member of the Coronavirus family which caused the worldwide pandemic of human respiratory illness coronavirus disease 2019 (COVID-19). Presumably emerging at the end of 2019, it poses a severe threat to public health and safety, with a high incidence of transmission, predominately through aerosols and/or direct contact with infected surfaces. In 2020, the search for vaccines began, leading to the obtaining of, to date, about twenty COVID-19 vaccines approved for use in at least one country. However, COVID-19 continues to spread and new genetic mutations and variants have been discovered, requiring pharmacological treatments. The most common therapies for COVID-19 are represented by antiviral and antimalarial agents, antibiotics, immunomodulators, angiotensin II receptor blockers, bradykinin B2 receptor antagonists and corticosteroids. In addition, nutraceuticals, vitamins D and C, omega-3 fatty acids and probiotics are under study. Finally, drug repositioning, which concerns the investigation of existing drugs for new therapeutic target indications, has been widely proposed in the literature for COVID-19 therapies. Considering the importance of this ongoing global public health emergency, this review aims to offer a synthetic up-to-date overview regarding diagnoses, variants and vaccines for COVID-19, with particular attention paid to the adopted treatments.

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“…Moreover, recently it has been shown that cysteamine is also capable of inhibiting infectivity of SARS-CoV-2 presumably by inhibiting the binding of S1 protein to ACE-2 receptor (14). Cysteamine and its disulfide cystamine also display an anti-inflammatory effect, reducing SARS-CoV-2 specific interferon-gamma production (15). In this report we examine the inhibitory activity of cysteamine in vitro against major variants of SARS-CoV-2 that have emerged so far and find that cysteamine inhibits them at achievable concentrations less than that currently approved by USFDA for ophthalmic use.…”

Section: Introductionmentioning

confidence: 99%

In VitroActivity of Cysteamine Against SARS-CoV-2 Variants

Thoene

Gavin²,

Towne

et al. 2021

Preprint

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Global COVID-19 pandemic is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Continuous emergence of new variants and their rapid spread are jeopardizing vaccine countermeasures to a significant extent. While currently available vaccines are effective at preventing illness associated with SARS-CoV-2 infection, these have been shown to be less effective at preventing breakthrough infection and transmission from a vaccinated individual to others. Here we demonstrate broad antiviral activity of cysteamine HCl in vitro against variants of SARS-CoV-2 assayed in a highly permissible Vero cell line. Cysteamine HCl inhibited infection of alpha, beta, gamma and delta variants effectively and the inhibitory activity was shown to manifest during the early stages of viral infection. Cysteamine is a very well-tolerated US FDA-approved drug used chronically as a topical ophthalmic solution to treat ocular cystinosis in patients who receive it hourly or QID lifelong at concentrations 3 to 4 times higher than that required to inhibit SARS CoV-2 in tissue culture. Application of cysteamine as a topical nasal treatment can potentially : 1) mitigate existing infection 2) prevent infection in exposed individuals, and 3) limit the contagion in vulnerable populations.

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Cysteamine with In Vitro Antiviral Activity and Immunomodulatory Effects Has the Potential to Be a Repurposing Drug Candidate for COVID-19 Therapy

Cited by 15 publications

References 46 publications

Cysteamine exerts in vitro antiviral activity against the SARS-CoV-2 Delta and Omicron variants

Cysteamine exerts in vitro antiviral activity against the SARS-CoV-2 Delta and Omicron variants

COVID-19 at a Glance: An Up-to-Date Overview on Variants, Drug Design and Therapies

In VitroActivity of Cysteamine Against SARS-CoV-2 Variants

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