| Autor: |
Grosche VR; Laboratory of Antiviral Research, Institute of Biomedical Science (ICBIM), Federal University of Uberlândia (UFU), Uberlândia 38405-317, Brazil.; Institute of Biosciences, Languages, and Exact Sciences (Ibilce), São Paulo State University (Unesp), São José do Rio Preto 15054-000, Brazil., Souza LPF; Innovation Center in Salivary Diagnostic and Nanobiotechnology, Institute of Biomedical Science (ICBIM), Federal University of Uberlândia (UFU), Uberlândia 38405-317, Brazil., Ferreira GM; Laboratory of Antiviral Research, Institute of Biomedical Science (ICBIM), Federal University of Uberlândia (UFU), Uberlândia 38405-317, Brazil., Guevara-Vega M; Innovation Center in Salivary Diagnostic and Nanobiotechnology, Institute of Biomedical Science (ICBIM), Federal University of Uberlândia (UFU), Uberlândia 38405-317, Brazil., Carvalho T; Institute of Biosciences, Languages, and Exact Sciences (Ibilce), São Paulo State University (Unesp), São José do Rio Preto 15054-000, Brazil., Silva RRDS; Center of Agrarian Science and Biodiversity, Federal University of Cariri (UFCA), Crato 63130-025, Brazil., Batista KLR; Laboratory of Microbial Pathogenesis, CEUMA University, São Luís 65045-380, Brazil., Abuna RPF; Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, Brazil.; Oswaldo Cruz Foundation (Fiocruz), Bi-Institutional Platform for Translational Medicine, Ribeirão Preto 14049-900, Brazil., Silva JS; Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, Brazil.; Oswaldo Cruz Foundation (Fiocruz), Bi-Institutional Platform for Translational Medicine, Ribeirão Preto 14049-900, Brazil., Calmon MF; Institute of Biosciences, Languages, and Exact Sciences (Ibilce), São Paulo State University (Unesp), São José do Rio Preto 15054-000, Brazil., Rahal P; Institute of Biosciences, Languages, and Exact Sciences (Ibilce), São Paulo State University (Unesp), São José do Rio Preto 15054-000, Brazil., da Silva LCN; Laboratory of Microbial Pathogenesis, CEUMA University, São Luís 65045-380, Brazil., Andrade BS; Laboratory of Bioinformatics and Computational Chemistry, State University of Southwest of Bahia, Jequié 45205-490, Brazil., Teixeira CS; Center of Agrarian Science and Biodiversity, Federal University of Cariri (UFCA), Crato 63130-025, Brazil., Sabino-Silva R; Innovation Center in Salivary Diagnostic and Nanobiotechnology, Institute of Biomedical Science (ICBIM), Federal University of Uberlândia (UFU), Uberlândia 38405-317, Brazil., Jardim ACG; Laboratory of Antiviral Research, Institute of Biomedical Science (ICBIM), Federal University of Uberlândia (UFU), Uberlândia 38405-317, Brazil.; Institute of Biosciences, Languages, and Exact Sciences (Ibilce), São Paulo State University (Unesp), São José do Rio Preto 15054-000, Brazil. |
| Abstrakt: |
The SARS-CoV-2 entry into host cells is mainly mediated by the interactions between the viral spike protein (S) and the ACE-2 cell receptor, which are highly glycosylated. Therefore, carbohydrate binding agents may represent potential candidates to abrogate virus infection. Here, we evaluated the in vitro anti-SARS-CoV-2 activity of two mannose-binding lectins isolated from the Brazilian plants Canavalia brasiliensis and Dioclea violacea (ConBR and DVL). These lectins inhibited SARS-CoV-2 Wuhan-Hu-1 strain and variants Gamma and Omicron infections, with selectivity indexes (SI) of 7, 1.7, and 6.5, respectively for ConBR; and 25, 16.8, and 22.3, for DVL. ConBR and DVL inhibited over 95% of the early stages of the viral infection, with strong virucidal effect, and also protected cells from infection and presented post-entry inhibition. The presence of mannose resulted in the complete lack of anti-SARS-CoV-2 activity by ConBR and DVL, recovering virus titers. ATR-FTIR, molecular docking, and dynamic simulation between SARS-CoV-2 S and either lectins indicated molecular interactions with predicted binding energies of -85.4 and -72.0 Kcal/Mol, respectively. Our findings show that ConBR and DVL lectins possess strong activities against SARS-CoV-2, potentially by interacting with glycans and blocking virus entry into cells, representing potential candidates for the development of novel antiviral drugs. |
