Cyclosporine A Inhibits Viral Infection and Release as Well as Cytokine Production in Lung Cells by Three SARS-CoV-2 Variants

Fenizia, Claudio; Galbiati, Silvia; Vanetti, Claudia; Vago, Riccardo; Clerici, Mario; Tacchetti, Carlo; Daniele, Tiziana

doi:10.1128/spectrum.01504-21

Cited by 24 publications

(16 citation statements)

References 91 publications

(90 reference statements)

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“…For the experiment, we used CLA—a parent peptide for 4B8M and cyclosporine (CsA), since CLA shares the mechanism of action with CsA [ 21 ]. In addition, CsA also exhibits antiviral activity [ 22 ]. The compounds were tested at the 5–75 µg/mL concentration range.…”

Section: Resultsmentioning

confidence: 99%

Antiviral Activity of a Cyclic Pro-Pro-β3-HoPhe-Phe Tetrapeptide against HSV-1 and HAdV-5

et al. 2022

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The core of Cyclolinopeptide A (CLA, cyclo(LIILVPPFF)), responsible for its high immunosuppressive activity, contains a Pro-Pro-Phe-Phe sequence. A newly synthesized cyclic tetrapeptide, cyclo(Pro-Pro-β3-HoPhe-Phe) (denoted as 4B8M) bearing the active sequence of CLA, was recently shown to exhibit a wide array of anti-inflammatory properties in mouse models. In this investigation, we demonstrate that the peptide significantly inhibits the replication of human adenovirus C serotype 5 (HAdV-5) and Herpes simplex virus type-1 (HSV-1) in epithelial lung cell line A-549, applying Cidofovir and Acyclovir as reference drugs. Based on a previously established mechanism of its action, we propose that the peptide may inhibit virus replication by the induction of PGE2 acting via EP2/EP4 receptors in epithelial cells. In summary, we reveal a new, antiviral property of this anti-inflammatory peptide.

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Section: Resultsmentioning

confidence: 99%

Antiviral Activity of a Cyclic Pro-Pro-β3-HoPhe-Phe Tetrapeptide against HSV-1 and HAdV-5

et al. 2022

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“…In 2011, de Wilde and colleagues first demonstrated the in vitro inhibitory activity of CsA at micromolar concentrations on the replication of different coronavirus genera [ 20 ]. The effective inhibition of replication towards SARS-CoV-2 has also recently been demonstrated by Fenizia et al on the human lung epithelium Calu3 cell line [ 19 ]. In addition, CsA anti-inflammatory and immunomodulatory activities would be beneficial in containing the cytokine storm experienced by many COVID-19 patients, leading to airway damage and respiratory loss of function [ 19 , 21 ].…”

Section: Introductionmentioning

confidence: 83%

“…Besides the effect on the prevention of allograft rejection, CsA has also been widely studied as a potential anti-viral drug [ 17 , 18 , 19 ]. In 2011, de Wilde and colleagues first demonstrated the in vitro inhibitory activity of CsA at micromolar concentrations on the replication of different coronavirus genera [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

An Enhanced Dissolving Cyclosporin-A Inhalable Powder Efficiently Reduces SARS-CoV-2 Infection In Vitro

et al. 2023

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This work illustrates the development of a dry inhalation powder of cyclosporine-A for the prevention of rejection after lung transplantation and for the treatment of COVID-19. The influence of excipients on the spray-dried powder’s critical quality attributes was explored. The best-performing powder in terms of dissolution time and respirability was obtained starting from a concentration of ethanol of 45% (v/v) in the feedstock solution and 20% (w/w) of mannitol. This powder showed a faster dissolution profile (Weibull dissolution time of 59.5 min) than the poorly soluble raw material (169.0 min). The powder exhibited a fine particle fraction of 66.5% and an MMAD of 2.97 µm. The inhalable powder, when tested on A549 and THP-1, did not show cytotoxic effects up to a concentration of 10 µg/mL. Furthermore, the CsA inhalation powder showed efficiency in reducing IL-6 when tested on A549/THP-1 co-culture. A reduction in the replication of SARS-CoV-2 on Vero E6 cells was observed when the CsA powder was tested adopting the post-infection or simultaneous treatment. This formulation could represent a therapeutic strategy for the prevention of lung rejection, but is also a viable approach for the inhibition of SARS-CoV-2 replication and the COVID-19 pulmonary inflammatory process.

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“…The analysis with ddPCR showed a decrease in viral particle number when no cholesterol is added, with amiodarone found to be the most effective cholesterol‐depleting antiviral drug among others 145 . Similar studies were also performed using computational drug repurposing, where existing drugs like cyclosporin A, azelastine etc., were evaluated for their antiviral efficacy and verified using ddPCR experiments by evaluating both in post‐infection stages and in periodic‐drug treatment and analysis 146,147 . Such studies show the importance of analysing and identifying new viral and drug induced mechanisms, in which dPCR can be utilitarian.…”

Section: Applications Of Digital Pcr In Sars‐cov‐2 Quantificationmentioning

confidence: 99%

SARS‐CoV‐2 in digital era: Diagnostic techniques and importance of nucleic acid quantification with digital PCRs

Aravind Kumar,

Aradhana,

Harleen

et al. 2023

Reviews in Medical Virology

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Studies related to clinical diagnosis and research of SARS‐CoV‐2 are important in the current pandemic era. Although molecular biology has emphasised the importance of qualitative analysis, quantitative analysis with nucleic acids in relation to SARS‐CoV‐2 needs to be clearly emphasised, which can provide perspective for viral dynamic studies of SARS‐CoV‐2. In this regard, the requirement and utilization of digital PCR in COVID‐19 research has substantially increased during the pandemic, necessitating the aggregation of its cardinal applications and future scopes. Hence, this meta‐review comprehensively addresses and emphasises the importance of nucleic acid quantification of SARS‐CoV‐2 RNA with digital PCR (dPCR). Various quantitative techniques of clinical significance like immunological, proteomic and nucleic acid‐based diagnosis and quantification, have been comparatively discussed. Furthermore, the core part of the article focusses on the working principle and advantages of digital PCR, along with its applications in COVID‐19 research. Several important applications like viral load quantitation, environmental surveillance and assay validation have been extensively investigated and discussed. Certain key future scopes of clinical importance, like mortality prediction, viral/variant‐symbiosis, and antiviral studies were also identified, suggesting several possible digital PCR applications in COVID‐19 research.

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Cyclosporine A Inhibits Viral Infection and Release as Well as Cytokine Production in Lung Cells by Three SARS-CoV-2 Variants

Cited by 24 publications

References 91 publications

Antiviral Activity of a Cyclic Pro-Pro-β3-HoPhe-Phe Tetrapeptide against HSV-1 and HAdV-5

Antiviral Activity of a Cyclic Pro-Pro-β3-HoPhe-Phe Tetrapeptide against HSV-1 and HAdV-5

An Enhanced Dissolving Cyclosporin-A Inhalable Powder Efficiently Reduces SARS-CoV-2 Infection In Vitro

SARS‐CoV‐2 in digital era: Diagnostic techniques and importance of nucleic acid quantification with digital PCRs

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