Mannose-Binding Lectins as Potent Antivirals against SARS-CoV-2

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Grosche, Victoria Riquena ; Souza, Leandro Peixoto Ferreira ; Ferreira, Giulia Magalhaes ; Guevara-Vega, Marco ; Carvalho, Tamara ; Silva, Romerio Rodrigues dos Santos ; Batista, Karla Lilian Rodrigues ; Abuna, Rodrigo Paolo Flores ; Silva, Joao Santana ; Calmon, Marilia de Freitas ; Rahal, Paula ; da Silva, Luis Claudio Nascimento ; Andrade, Bruno Silva ; Teixeira, Claudener Souza ; Sabino-Silva, Robinson ; Jardim, Ana Carolina Gomes

• Tipo de documento: Artigo Científico
• Fonte: Viruses-Basel; v. 15, n. 9, p. 26-pg., 2023-09-01.

Resumo

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. (AU)

• Processo FAPESP: 21/00603-3 - Análise do viroma de carrapatos coletados em animais silvestres
• Beneficiário: Paula Rahal
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 19/07784-3 - Estudo in vitro da ação de peptídeos sintéticos como antivirais contra CHIKV
• Beneficiário: Marilia de Freitas Calmon
• Modalidade de apoio: Auxílio à Pesquisa - Regular