Polyunsaturated ω‑3 fatty acids inhibit ACE2‑controlled SARS‑CoV‑2 binding and cellular entry

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Goc A, Niedzwiecki A, Rath M

The strain SARS-CoV-2, newly emerged in late 2019, has been identifed as the cause of COVID19 and the pandemic declared by WHO in early 2020. Although lipids have been shown to possess antiviral efcacy, little is currently known about lipid compounds with anti-SARS-CoV-2 binding and entry properties. To address this issue, we screened, overall, 17 polyunsaturated fatty acids, monounsaturated fatty acids and saturated fatty acids, as wells as lipid-soluble vitamins. In performing target-based ligand screening utilizing the RBD-SARS-CoV-2 sequence, we observed that polyunsaturated fatty acids most efectively interfere with binding to hACE2, the receptor for SARSCoV-2. Using a spike protein pseudo-virus, we also found that linolenic acid and eicosapentaenoic acid signifcantly block the entry of SARS-CoV-2. In addition, eicosapentaenoic acid showed higher efcacy than linolenic acid in reducing activity of TMPRSS2 and cathepsin L proteases, but neither of the fatty acids afected their expression at the protein level. Also, neither reduction of hACE2 activity nor binding to the hACE2 receptor upon treatment with these two fatty acids was observed. Although further in vivo experiments are warranted to validate the current fndings, our study provides a new insight into the role of lipids as antiviral compounds against the SARS-CoV-2 strain.


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