bioRxivBiochemistry
Unveiling the antiviral capabilities of targeting Human Dihydroorotate Dehydrogenase against SARS-CoV-2
A. Purificacao, S. Silva-Mendonca, L. Cruz, C. Sacramento, J. Temerozo, N. Fintelman-Rodrigues, C. Freitas, B. Godoi, M. Vaidergorn, J. Leite, L. Alvarez, M. Freitas, M. Silva, B. Martin, R. Lopez, B. Neves, F. Costa, T. Souza, F. Emery, C. Andrade, C. Nonato
Abstract
The urgent need for effective treatments against emerging viral diseases, driven by drug-resistant strains and new viral variants, remains critical. We focus on inhibiting the human dihydroorotate dehydrogenase (HsDHODH), one of the enzymes in charge of pyrimidine nucleotide synthesis. This strategy could impede viral replication without provoking resistance. We evaluated quinone-based compounds, discovering potent HsDHODH inhibition (low nanomolar IC50) and promising in vitro anti-SARS-CoV-2 activity (low micromolar EC50). These compounds exhibited low toxicity, indicating potential for further development. Additionally, we employed computational tools like molecular docking and QSAR models to analyze protein-ligand interactions. These findings represent a significant step forward in the search for effective antiviral treatments and have great potential to impact the development of new broad-spectrum antiviral drugs.
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