Recent reviews on cyclodextrins against SARS-CoV-2

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Recent reviews emphasized the role of membrane lipids in the infectivity mechanism of SARS-COV-2. Cholesterol-rich parts of cell membranes serve as docking places of host cells for the viruses. Coronavirus 2 is a member of a virus family with lipid envelope that fuses with host cell through endocytosis, internalizing its components in the cell. In vitro cell models have shown that depletion of cholesterol by cyclodextrin, and particularly methyl beta cyclodextrin disturb the host cell membrane lipid composition this way, reducing the attachment of the virus to the protein receptors. [1]

Cholesterol-binding agents, including statins or methyl-β-cyclodextrin (MβCD), can affect cholesterol, causing disruption of lipid rafts, consequently impairing coronavirus adhesion and binding. Moreover, these compounds can block downstream key molecules in virus infectivity, reducing the levels of proinflammatory molecules [tumor necrosis factor alpha (TNF-α), interleukin (IL)-6], and/or affecting the autophagic process involved in both viral replication and clearance. Furthermore, cyclodextrins can assemble into complexes with various drugs to form host-guest inclusions and may be used as pharmaceutical excipients of antiviral compounds, such as lopinavir and remdesivir, by improving bioavailability and solubility. In conclusion, the role of lipid rafts-affecting drugs in the process of coronavirus entry into the host cells prompts to introduce a new potential task in the pharmacological approach against coronavirus. [2]

The Niemann Pick type C (NPC) disease-causing gene (NPC1) has been strongly associated with viral infection, both as a filovirus receptor (e.g., Ebola) and through LE/L lipid trafficking. This suggests that NPC1 inhibitors or NPC disease mimetics could serve as anti-SARS-CoV-2 agents. Fortunately, there are such clinically approved molecules that elicit antiviral activity in preclinical studies, without causing NP-C disease. Inhibition of NPC1 may impair viral SARS-CoV-2 infectivity via several lipid-dependent mechanisms, which disturb the microenvironment optimum for viral infectivity. [3]


1 Sofiane Fatmi 1, Lamia Taouzinet 1, Mohamed Skiba 2, Mokrane Iguer-Ouada (2021) The Use of Cyclodextrin or its Complexes as a Potential Treatment Against the 2019 Novel Coronavirus: A Mini-Review. Curr Drug Deliv 18(4):382-386. doi: 10.2174/1567201817666200917124241.

2 Maurizio Sorice, Roberta Misasi, Gloria Riitano, Valeria Manganelli, Stefano Martellucci, Agostina Longo, Tina Garofalo, Vincenzo Mattei (2021) Targeting Lipid Rafts as a Strategy Against Coronavirus. Front Cell Dev Biol 8:618296. doi: 10.3389/fcell.2020.618296.

3 Stephen L Sturley, Tamayanthi Rajakumar, Natalie Hammond, Katsumi Higaki, Zsuzsa Márka, Szabolcs Márka, Andrew B Munkacsi (2020) Potential COVID-19 therapeutics from a rare disease: weaponizing lipid dysregulation to combat viral infectivity. J Lipid Res 61(7):972-982. doi: 10.1194/jlr.R120000851


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