Aline D Purificação, Sabrina Silva-Mendonça, Luiza V Cruz, Carolina Q Sacramento, Jairo R Temerozo, Natalia Fintelman-Rodrigues, Caroline Souza de Freitas, Bruna Fleck Godoi, Miguel Menezes Vaidergorn, Juliana Almeida Leite, Luis Carlos Salazar Alvarez, Murillo V Freitas, Meryck F B Silvac, Bianca A Martin, Renata F V Lopez, Bruno J Neves, Fabio T M Costa, Thiago M L Souza, Flavio da Silva Emery, Carolina Horta Andrade, M Cristina Nonato
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 ( Hs DHODH), one of the main enzymes responsible for pyrimidine nucleotide synthesis. This strategy could impede viral replication without provoking resistance. We evaluated naphthoquinone fragments, discovering potent Hs DHODH inhibition with IC50 ranging from 48 to 684 nM, and promising in vitro anti-SARS-CoV-2 activity with EC50 ranging from 1...
March 12, 2024: ACS Omega