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In vitro and clinical studies on the efficacy of α-cyclodextrin and hydroxytyrosol against SARS-CoV-2 infection
S Paolacci1, M C Ergoren, D De Forni
1MAGI'S LAB, Rovereto (TN), Italy. stefano.paolacci@assomagi.org.
Objective:
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new coronavirus responsible for the current pandemic of coronavirus disease 2019 (COVID-19). This virus attacks cells of the airway epithelium by binding transmembrane angiotensin-converting enzyme 2 (ACE2). Hydroxytyrosol has anti-viral properties. Alpha-cyclodextrin can deplete sphingolipids and phospholipids from cell membranes. The aim of the present experimental study was to evaluate the efficacy of α-cyclodextrin and hydroxytyrosol in improving defenses against SARS-CoV-2 infection in in vitro cell models and humans.
Patients And Methods:
For in vitro experiments on Vero E6 cells, RNA for RT-qPCR analysis was extracted from Caco2 and human fibroblast cell lines. For study in humans, the treatment group consisted of 149 healthy volunteers in Northern Cyprus, considered at higher risk of SARS-CoV-2 infection than the general population. The volunteers used nasal spray containing α-cyclodextrin and hydroxytyrosol for 4 weeks. The control group consisted of 76 healthy volunteers who did not use the spray.
Results:
RT-qPCR experiments on targeted genes involved in endocytosis showed a reduction in gene expression, whereas cytotoxicity and cytoprotective tests showed that the compounds exerted a protective effect against SARS-CoV-2 infection at non-cytotoxic concentrations. None of the volunteers became positive to SARS-CoV-2 RT-qPCR assay during the 30 days of treatment.
Conclusions:
Treatment with α-cyclodextrin and hydroxytyrosol nasal spray improved defenses against SARS-CoV-2 infection and reduced synthesis of viral particles.
Insights
A nasal spray containing alpha-cyclodextrin and hydroxytyrosol demonstrated efficacy in enhancing defenses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This treatment reduced viral particle synthesis and prevented infections in human volunteers.
Area of Science:
- Virology
- Cell Biology
- Pharmacology
Background:
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19 by targeting airway epithelial cells via ACE2.
- Hydroxytyrosol exhibits known antiviral properties.
- Alpha-cyclodextrin can alter cell membrane composition.
Purpose of the Study:
- To assess the effectiveness of alpha-cyclodextrin and hydroxytyrosol in bolstering defenses against SARS-CoV-2.
- To evaluate these compounds in both in vitro cell models and human subjects.
Main Methods:
- In vitro studies utilized Vero E6, Caco2, and human fibroblast cell lines for RT-qPCR analysis.
- Human trials involved 149 healthy volunteers using a nasal spray with alpha-cyclodextrin and hydroxytyrosol for 4 weeks, compared to 76 controls.
- RT-qPCR, cytotoxicity, and cytoprotective assays were performed.
Main Results:
- In vitro experiments showed reduced gene expression related to endocytosis and a protective effect against SARS-CoV-2 at non-cytotoxic concentrations.
- Human volunteers using the nasal spray showed no SARS-CoV-2 RT-qPCR positive results during the 30-day treatment period.
Conclusions:
- The combination of alpha-cyclodextrin and hydroxytyrosol in a nasal spray formulation enhances host defenses against SARS-CoV-2.
- This intervention effectively reduces the synthesis of viral particles and prevents infection.
