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

• Type: Article in International Scientific Journal
• Date: 2023

Authors

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

Journal

Title: Molecules

Vol. 28 No. 3

Final page: 7204

ISSN: 1420-3049

Publisher: MDPI

Indexing

ISI Web of Knowledge - 2 Citations

Scopus - 2 Citations

Other information

Authenticus ID: 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 19