Phenolic compounds disrupt spike-mediated receptor-binding and entry of SARS-CoV-2 pseudo-virions
Anna Goc, Waldemar Sumera, Matthias Rath, Aleksandra Niedzwiecki
PLOS ONE, doi:10.1371/journal.pone.0253489
In the pursuit of suitable and effective solutions to SARS-CoV-2 infection, we investigated the efficacy of several phenolic compounds in controlling key cellular mechanisms involved in its infectivity. The way the SARS-CoV-2 virus infects the cell is a complex process and comprises four main stages: attachment to the cognate receptor, cellular entry, replication and cellular egress. Since, this is a multi-part process, it creates many opportunities to develop effective interventions. Targeting binding of the virus to the host receptor in order to prevent its entry has been of particular interest. Here, we provide experimental evidence that, among 56 tested polyphenols, including plant extracts, brazilin, theaflavin-3,3'-digallate, and curcumin displayed the highest binding with the receptor-binding domain of spike protein, inhibiting viral attachment to the human angiotensin-converting enzyme 2 receptor, and thus cellular entry of pseudo-typed SARS-CoV-2 virions. Both, theaflavin-3,3'-digallate at 25 μg/ml and curcumin above 10 μg/ml concentration, showed binding with the angiotensin-converting enzyme 2 receptor reducing at the same time its activity in both cell-free and cell-based assays. Our study also demonstrates that brazilin and theaflavin-3,3'-digallate, and to a still greater extent, curcumin, decrease the activity of transmembrane serine protease 2 both in cell-free and cell-based assays. Similar pattern was observed with cathepsin L, although only theaflavin-3,3'-digallate showed a modest diminution of cathepsin L expression at protein level. Finally, each of these three compounds moderately increased endosomal/lysosomal pH. In conclusion, this study demonstrates pleiotropic anti-SARS-CoV-2 efficacy of specific polyphenols and their prospects for further scientific and clinical investigations.
Supporting information
S1 File. Raw Western blot images. (PPTX)
Author Contributions Conceptualization: Anna Goc.
Data curation: Matthias Rath, Aleksandra Niedzwiecki. Formal analysis: Anna Goc, Waldemar Sumera. Visualization: Anna Goc, Waldemar Sumera, Aleksandra Niedzwiecki. Writing -original draft: Anna Goc, Waldemar Sumera, Matthias Rath, Aleksandra Niedzwiecki. Writing -review & editing: Anna Goc, Waldemar Sumera, Aleksandra Niedzwiecki.
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'abstract': '<jats:p>In the pursuit of suitable and effective solutions to SARS-CoV-2 infection, we '
'investigated the efficacy of several phenolic compounds in controlling key cellular '
'mechanisms involved in its infectivity. The way the SARS-CoV-2 virus infects the cell is a '
'complex process and comprises four main stages: attachment to the cognate receptor, cellular '
'entry, replication and cellular egress. Since, this is a multi-part process, it creates many '
'opportunities to develop effective interventions. Targeting binding of the virus to the host '
'receptor in order to prevent its entry has been of particular interest. Here, we provide '
'experimental evidence that, among 56 tested polyphenols, including plant extracts, brazilin, '
'theaflavin-3,3’-digallate, and curcumin displayed the highest binding with the '
'receptor-binding domain of spike protein, inhibiting viral attachment to the human '
'angiotensin-converting enzyme 2 receptor, and thus cellular entry of pseudo-typed SARS-CoV-2 '
'virions. Both, theaflavin-3,3’-digallate at 25 μg/ml and curcumin above 10 μg/ml '
'concentration, showed binding with the angiotensin-converting enzyme 2 receptor reducing at '
'the same time its activity in both cell-free and cell-based assays. Our study also '
'demonstrates that brazilin and theaflavin-3,3’-digallate, and to a still greater extent, '
'curcumin, decrease the activity of transmembrane serine protease 2 both in cell-free and '
'cell-based assays. Similar pattern was observed with cathepsin L, although only '
'theaflavin-3,3’-digallate showed a modest diminution of cathepsin L expression at protein '
'level. Finally, each of these three compounds moderately increased endosomal/lysosomal pH. In '
'conclusion, this study demonstrates pleiotropic anti-SARS-CoV-2 efficacy of specific '
'polyphenols and their prospects for further scientific and clinical investigations.</jats:p>',
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