Unveiling the Antiviral Capabilities of Targeting Human Dihydroorotate Dehydrogenase against SARS-CoV-2.

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 main enzymes responsible for pyrimidine nucleotide synthesis. This strategy could impede viral replication without provoking resistance. We evaluated naphthoquinone fragments, discovering potent HsDHODH inhibition with IC₅₀ ranging from 48 to 684 nM, and promising in vitro anti-SARS-CoV-2 activity with EC₅₀ ranging from 1.2 to 2.3 μM. These compounds exhibited low toxicity, indicating potential for further development. Additionally, we employed computational tools such as molecular docking and quantitative structure-ac

SUBMITTER: Purificacao AD 

PROVIDER: S-EPMC10938441 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature