Pilot study for the evaluation of safety profile of a potential inhibitor of SARS-CoV-2 endocytosis

Main Article Content

Stefano Paolacci
Maria Rachele Ceccarini
Michela Codini
Elena Manara
Silvia Tezzele
Marcella Percio
Natale Capodicasa
Dorela Kroni
Munis Dundar
Mahmut Cerkez Ergoren
Tamer Sanlidag
Tommaso Beccari
Marco Farronato
Giampietro Farronato
Gianluca Martino Tartaglia
Matteo Bertelli




Background and aim of the work: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current pandemics of coronavirus disease. This virus is able to attack the cells of the airway epithelium by binding to the transmembrane angiotensin I converting enzyme 2 (ACE2). We developed an oral spray that could inhibit the SARS-CoV-2 endocytosis. The spray contains hydroxytyrosol for its anti-viral, anti-inflammatory and anti-oxidant properties, and α-cyclodextrin for its ability to deplete sphingolipids, that form the lipid rafts where ACE2 localizes. The aim of the present pilot multi-centric open non-controlled observational study was to evaluate the safety profile of the “Endovir Stop” spray. Methods: An MTT test was performed to evaluate cytotoxicity of the spray in two human cell lines. An oxygen radical absorbance capacity assay was performed to evaluate the antioxidant capacity of the spray. The spray was also tested on 87 healthy subjects on a voluntary basis. Results: The MTT test revealed that the spray is not cytotoxic. The ORAC assay showed a good antioxidant capacity for the spray. Endovir Stop tested on healthy volunteers showed the total absence of side effects and drug interactions during the treatment. Conclusions: We demonstrated that Endovir Stop spray is safe. The next step would be the administration of the efficacy of the spray by testing it to a wider range of people and see whether there is a reduced infection rate of SARS-CoV-2 in the treated subjects than in the non-treated individuals.


Download data is not yet available.
Abstract 1770 | PDF Downloads 401


1. Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020; 181(2): 271-280.e8
2. Shulla A. Cofactors in coronavirus entry. Dissertations 2011; 284. https://ecommons.luc.edu/luc_diss/284
3. Tay MZ, Poh CM, Rénia L, MacAry PA, Ng LFP. The trinity of COVID-19: immunity, inflammation and intervention. Nat Rev Immunol 2020; 20(6): 363-374
4. Bertelli M, Kiani AK, Paolacci S, et al. Hydroxytyrosol: A natural compound with promising pharmacological activities. J Biotechnol 2020; 309: 29-33
5. Li G, Kim J, Huang Z, St Clair JR, Brown DA, London E. Efficient replacement of plasma membrane outer leaflet phospholipids and sphingolipids in cells with exogenous lipids. Proc Natl Acad Sci USA 2016; 113: 14025-30
6. Aden DP, Fogel A, Plotkin S, Damjanov I, Knowles BB. Controlled synthesis of HBsAg in a differentiated human liver carcinoma-derived cell line. Nature 1979; 282: 615-6
7. Knowles BB, Howe CC, Aden DP. Human hepatocellular carcinoma cell lines secrete the major plasma proteins and hepatitis B surface antigen. Science 1980; 209: 497-9
8. Grindstaff KK, Blanco G, Mercer RW. Translational regulation of Na,K-ATPase alpha1 and beta1 polypeptide expression in epithelial cells. J Biol Chem. 1996; 271: 23211-21
9. Ceccarini MR, Vannini S, Cataldi S, et al. In vitro protective effects of Lycium barbarum Berries cultivated in Umbria (Italy) on human hepatocellular carcinoma cells. Biomed Res Int 2016: 7529521
10. Pagano C, Ceccarini MR, Calarco P, et al. Bioadhesive polymeric films based on usnic acid for burn wound treatment: Antibacterial and cytotoxicity studies. Colloids Surf B Biointerfaces 2019; 178: 488-99
11. Patria FF, Ceccarini MR, Codini M, et al. A role for neutral sphingomyelinase in wound healing induced by keratinocyte proliferation upon 1α, 25-dihydroxyvitamin D3 treatment. Int J Mol Sci 2019; 20(15).
12. Pagano C, Marinozzi M, Baiocchi C, et al. Bioadhesive polymeric films based on red onion skins extract for wound treatment: An innovative and eco-friendly formulation. Molecules 2020; 25(2).
13. Persichetti E., De Michele A., Codini M., Traina G. Antioxidative capacity of Lactobacillus fermentum LF31 evaluated invitro by oxygen radical absorbance capacity assay. Nutrition 2014; 30(7-8): 936–8
14. Zulueta A, Maurizi A, Frígola A, Esteve MJ, Coli R, Burini G. Antioxidant capacity of cow milk, whey and deproteinized milk. International Dairy Journal 2009; 19(6-7): 380–5
15. Codini M, Tringaniello C, Cossignani L, et al. Relationship between fatty acids composition/antioxidant potential of breast milk and maternal diet: Comparison with infant formulas. Molecules 2020; 25(12): E2910

Most read articles by the same author(s)

<< < 1 2 3 4 5 > >>