Evaluation of the Cytotoxic and Antiviral Effects of Small Molecules Selected by In Silico Studies as Inhibitors of SARS-CoV-2 Cell Entry

• Tipo: Artigo em Revista Científica Internacional
• Data: 2023

Autores

Carvalhal, F (Autor) Outra; Magalhaes, AC (Autor) Outra; Rebelo, R (Autor) Outra; Palmeira, A (Autor) FFUP; Resende, DISP (Autor) Outra; Duraes, F (Autor) Outra; Maia, M (Autor) Outra; Xavier, CPR (Autor) Outra; Pereira, L (Autor) Outra; Emilia Sousa (Autor) FFUP; Marta Correia da Silva (Autor) FFUP; Helena Vasconcelos, MH (Autor) FFUP

Revista

Título: Molecules

Vol. 28 Nº 3

Página Final: 7204

ISSN: 1420-3049

Editora: MDPI

Indexação

ISI Web of Knowledge - 2 Citações

Scopus - 2 Citações

Outras Informações

ID Authenticus: P-00Z-A3W

DOI: 10.3390/molecules28207204

Abstract (EN): The spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) relies on host cell surface glycans to facilitate interaction with the angiotensin-converting enzyme 2 (ACE-2) receptor. This interaction between ACE2 and the spike protein is a gateway for the virus to enter host cells and may be targeted by antiviral drugs to inhibit viral infection. Therefore, targeting the interaction between these two proteins is an interesting strategy to prevent SARS-CoV-2 infection. A library of glycan mimetics and derivatives was selected for a virtual screening performed against both ACE2 and spike proteins. Subsequently, in vitro assays were performed on eleven of the most promising in silico compounds to evaluate: (i) their efficacy in inhibiting cell infection by SARS-CoV-2 (using the Vero CCL-81 cell line as a model), (ii) their impact on ACE2 expression (in the Vero CCL-81 and MDA-MB-231 cell lines), and (iii) their cytotoxicity in a human lung cell line (A549). We identified five synthetic compounds with the potential to block SARS-CoV-2 infection, three of them without relevant toxicity in human lung cells. Xanthene 1 stood out as the most promising anti-SARS-CoV-2 agent, inhibiting viral infection and viral replication in Vero CCL-81 cells, without causing cytotoxicity to human lung cells.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 19