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Molecular insights to the anti-COVID-19 potential of α-, β- and γ-cyclodextrins.
- Source :
-
Journal of biomolecular structure & dynamics [J Biomol Struct Dyn] 2023 Dec 20, pp. 1-11. Date of Electronic Publication: 2023 Dec 20. - Publication Year :
- 2023
- Publisher :
- Ahead of Print
-
Abstract
- SARS-CoV-2 viral infection is regulated by the host cell receptors ACE2 and TMPRSS2, and therefore the effect of various natural and synthetic compounds on these receptors has recently been the subject of investigations. Cyclodextrins, naturally occurring polysaccharides derived from starch, are soluble in water and have a hydrophobic cavity at their center enabling them to accommodate small molecules and utilize them as carriers in the food, supplements, and pharmaceutical industries to improve the solubility, stability, and bioavailability of target compounds. In the current study, computational molecular simulations were used to investigate the ability of α-, β- and γ-Cyclodextrins on human cell surface receptors. Cell-based experimental approaches, including expression analyses at mRNA and protein levels and virus replication, were used to assess the effect on receptor expression and virus infection, respectively. We found that none of the three CDs could dock effectively to human cell surface receptor ACE2 and viral protease M <superscript>pro</superscript> (essential for virus replication). On the other hand, α- and β-CD showed strong and stable interactions with TMPRSS2, and the expression of both ACE2 and TMPRSS2 was downregulated at the mRNA and protein levels in cyclodextrin (CD)-treated cells. A cell-based virus replication assay showed ∼20% inhibition by β- and γ-CD. Taken together, the study suggested that (i) downregulation of expression of host cell receptors may not be sufficient to inhibit virus infection (ii) activity of the receptors and virus protein M <superscript>pro</superscript> may play a critical and clinically relevant role, and hence (iii) newly emerging anti-Covid-19 compounds warrant multimodal functional analyses.Communicated by Ramaswamy H. Sarma.
Details
- Language :
- English
- ISSN :
- 1538-0254
- Database :
- MEDLINE
- Journal :
- Journal of biomolecular structure & dynamics
- Publication Type :
- Academic Journal
- Accession number :
- 38116950
- Full Text :
- https://doi.org/10.1080/07391102.2023.2294385