{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T03:39:44Z","timestamp":1791085184595,"version":"4.1.0"},"reference-count":109,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,2,27]],"date-time":"2022-02-27T00:00:00Z","timestamp":1645920000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council","doi-asserted-by":"publisher","award":["ALLRP 554328 - 20"],"award-info":[{"award-number":["ALLRP 554328 - 20"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The overall impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on our society is unprecedented. The identification of small natural ligands that could prevent the entry and\/or replication of the coronavirus remains a pertinent approach to fight the coronavirus disease (COVID-19) pandemic. Previously, we showed that the phenolic compounds corilagin and 1,3,6-tri-O-galloyl-\u03b2-D-glucose (TGG) inhibit the interaction between the SARS-CoV-2 spike protein receptor binding domain (RBD) and angiotensin-converting enzyme 2 (ACE2), the SARS-CoV-2 target receptor on the cell membrane of the host organism. Building on these promising results, we now assess the effects of these phenolic ligands on two other crucial targets involved in SARS-CoV-2 cell entry and replication, respectively: transmembrane protease serine 2 (TMPRSS2) and 3-chymotrypsin like protease (3CLpro) inhibitors. Since corilagin, TGG, and tannic acid (TA) share many physicochemical and structural properties, we investigate the binding of TA to these targets. In this work, a combination of experimental methods (biochemical inhibition assays, surface plasmon resonance, and quartz crystal microbalance with dissipation monitoring) confirms the potential role of TA in the prevention of SARS-CoV-2 infectivity through the inhibition of extracellular RBD\/ACE2 interactions and TMPRSS2 and 3CLpro activity. Moreover, molecular docking prediction followed by dynamic simulation and molecular mechanics Poisson\u2013Boltzmann surface area (MMPBSA) free energy calculation also shows that TA binds to RBD, TMPRSS2, and 3CLpro with higher affinities than TGG and corilagin. Overall, these results suggest that naturally occurring TA is a promising candidate to prevent and inhibit the infectivity of SARS-CoV-2.<\/jats:p>","DOI":"10.3390\/ijms23052643","type":"journal-article","created":{"date-parts":[[2022,2,27]],"date-time":"2022-02-27T20:47:17Z","timestamp":1645994837000},"page":"2643","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Molecular Interactions of Tannic Acid with Proteins Associated with SARS-CoV-2 Infectivity"],"prefix":"10.3390","volume":"23","author":[{"given":"Mohamed","family":"Haddad","sequence":"first","affiliation":[{"name":"Centre Armand-Frappier Sant\u00e9 Biotechnologie, 531 Boulevard des Prairies, Laval, QC H7V 1B7, Canada"},{"name":"Institute on Nutrition and Functional Foods, Laval University, Quebec City, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6095-6077","authenticated-orcid":false,"given":"Roger","family":"Gaudreault","sequence":"additional","affiliation":[{"name":"Succursale Centre-Ville, D\u00e9partment de Physique, Universit\u00e9 de Montr\u00e9al, Case Postale 6128, Montr\u00e9al, QC H3C 3J7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Sasseville","sequence":"additional","affiliation":[{"name":"Succursale Centre-Ville, D\u00e9partment de Physique, Universit\u00e9 de Montr\u00e9al, Case Postale 6128, Montr\u00e9al, QC H3C 3J7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phuong Trang","family":"Nguyen","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Chimie, Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al, 2101 Rue Jeanne-Mance, Montr\u00e9al, QC H2X 2J6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Wiebe","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Chimie, Universit\u00e9 McGill, 3420 Rue University, Montr\u00e9al, QC H3A 2A7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theo","family":"Van De Ven","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Chimie, Universit\u00e9 McGill, 3420 Rue University, Montr\u00e9al, QC H3A 2A7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5563-8787","authenticated-orcid":false,"given":"Steve","family":"Bourgault","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Chimie, Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al, 2101 Rue Jeanne-Mance, Montr\u00e9al, QC H2X 2J6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Normand","family":"Mousseau","sequence":"additional","affiliation":[{"name":"Succursale Centre-Ville, D\u00e9partment de Physique, Universit\u00e9 de Montr\u00e9al, Case Postale 6128, Montr\u00e9al, QC H3C 3J7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3252-5878","authenticated-orcid":false,"given":"Charles","family":"Ramassamy","sequence":"additional","affiliation":[{"name":"Centre Armand-Frappier Sant\u00e9 Biotechnologie, 531 Boulevard des Prairies, Laval, QC H7V 1B7, Canada"},{"name":"Institute on Nutrition and Functional Foods, Laval University, Quebec City, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1038\/s41586-021-04245-0","article-title":"The N501Y spike substitution enhances SARS-CoV-2 infection and transmission","volume":"602","author":"Liu","year":"2021","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1038\/s41586-021-03944-y","article-title":"SARS-CoV-2 B. 1.617. 2 Delta variant replication and immune evasion","volume":"599","author":"Mlcochova","year":"2021","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/j.cell.2021.12.046","article-title":"SARS-CoV-2 Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses","volume":"185","author":"Dejnirattisai","year":"2022","journal-title":"Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1038\/s41557-021-00758-3","article-title":"A glycan gate controls opening of the SARS-CoV-2 spike protein","volume":"13","author":"Sztain","year":"2021","journal-title":"Nat. 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