A pilot study on the preventative potential of alpha-cyclodextrin and hydroxytyrosol against SARS-CoV-2 transmission
Keywords:
SARS-CoV-2, ACE2, hydroxytyrosol, α-cyclodextrinAbstract
Background and aim of the work: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current pandemics. This virus attacks the cells by binding to the transmembrane angiotensin I converting enzyme 2. In this study, we experimented a food supplement containing alpha-cyclodextrin and hydroxytyrosol for the improvement of the defenses against the SARS-CoV-2. Hydroxytyrosol has anti-viral properties and is able to reduce the serum lipids in mice. α-cyclodextrin has the ability to deplete sphingolipids and phospholipids from the cellular membranes. The aim of the present preliminary open non-controlled interventional study was to evaluate the efficacy of alpha-cyclodextrin and hydroxytyrosol in improving defenses against SARS-CoV-2. Methods: Fifty healthy volunteers at a higher risk of SARS-CoV-2 infection from Northern Cyprus and six positive individuals for SARS-CoV-2 were enrolled in this study. The in silico prediction was performed using D3DOCKING to evaluate the interactions of hydroxytyrosol and alpha-cyclodextrin with proteins involved in the SARS-CoV-2 endocytosis. Results: The 50 volunteers did not become positive in 15 days for SARS-CoV-2 after the administration of the compound for two weeks, despite they were at higher risk of infection than the general population. Interestingly, in the cohort of six positive patients, two patients were administered the spray and became negative after five days, despite the viral load was higher in the treated subjects than the untreated patients who became negative after ten days. In addition, we identified possible interactions among hydroxytyrosol and alpha-cyclodextrin with the protein Spike and the human proteins ACE2 and TMPRSS2. Conclusions: We reported on the results of the possible role of alpha-cyclodextrin and hydroxytyrosol in improving defenses against SARS-CoV-2. The next step will be the administration of the compound to a larger cohort in a controlled study to confirm the reduction of the infection rate of SARS-CoV-2 in the treated subjects.
References
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
Shulla A. Cofactors in coronavirus entry. Dissertations 2011; 284. https://ecommons.luc.edu/luc_diss/284
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
Bertelli M, Kiani AK, Paolacci S, et al. Hydroxytyrosol: A natural compound with promising pharmacological activities. J Biotechnol 2020; 309: 29-33
Jemai H, Fki I, Bouaziz M, Bouallagui Z, El Feki A, Isoda H, Sayadi S. Lipid-lowering and antioxidant effects of hydroxytyrosol and its triacetylated derivative recovered from olive tree leaves in cholesterol-fed rats. J Agric Food Chem 2008; 56: 2630-6
Lopez S, Bermudez B, Montserrat-de la Paz S, et al. Membrane composition and dynamics: a target of bioactive virgin olive oil constituents. Biochim Biophys Acta 2014; 1838: 1638-56
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
Yamada K, Ogawa H, Hara A, et al. Mechanism of the antiviral effect of hydroxytyrosol on influenza virus appears to involve morphological change of the virus. Antiviral Res 2009; 83(1): 35-44
Ramírez-Expósito MJ, Martínez-Martos JM. Anti-inflammatory and antitumor effects of hydroxytyrosol but not oleuropein on experimental glioma in vivo. A putative role for the renin-angiotensin system. Biomedicines 2018; 6(1): 11
Hu B, Huang S, Yin L. The cytokine storm and COVID-19. J Med Virol 2020; 10.1002/jmv.26232
http://www.asdera.com/sars-nutrition.html
https://www.d3pharma.com/D3Targets-2019-nCoV/D3Docking/index.php
https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX%3A32008D0413
https://eur-lex.europa.eu/legal-content/EN/TXT/?qid=1599641462302&uri=CELEX:32017D2373
Campione E, Lanna C, Cosio T, et al. Pleiotropic effect of Lactoferrin in the prevention and treatment of COVID-19 infection: randomized clinical trial, in vitro and in silico preliminary evidences. bioRxiv 2020; 2020.08.11.244996
Abian O, Ortega-Alarcon D, Jimenez-Alesanco A, et al. Structural stability of SARS-CoV-2 3CLpro and identification of quercetin as an inhibitor by experimental screening. Int J Biol Macromol 2020; 164: 1693–703
Paolacci S, Ceccarini MR, Codini M, et al. Pilot study for the evaluation of safety profile of a potential inhibitor of SARS-CoV-2 endocytosis. Acta Bio Med 2020; 91: e2020009.
Downloads
Published
Issue
Section
License
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Transfer of Copyright and Permission to Reproduce Parts of Published Papers.
Authors retain the copyright for their published work. No formal permission will be required to reproduce parts (tables or illustrations) of published papers, provided the source is quoted appropriately and reproduction has no commercial intent. Reproductions with commercial intent will require written permission and payment of royalties.