Design, synthesis and biological evaluations of niclosamide analogues against SARS-CoV-2.

ABSTRACT: Niclosamide, a widely-used anthelmintic drug, inhibits SARS-CoV-2 virus entry through TMEM16F inhibition and replication through autophagy induction, but the relatively high cytotoxicity and poor oral bioavailability limited its application. We synthesized 22 niclosamide analogues of which compound 5 was found to exhibit the best anti-SARS-CoV-2 efficacy (IC₅₀ = 0.057 μ M) and compounds 6, 10, and 11 (IC₅₀ = 0.39, 0.38, and 0.49 μ M, respectively) showed comparable efficacy to niclosamide. On the other hand, compounds 5, 6, 11 contained higher stability in human plasma and liver S9 enzymes assay than niclosamide, which could improve bioavailability and half-life when administered orally. Fluorescence microscopy revealed that compound 5 exhibited better activity in the

SUBMITTER: Juang YP 

PROVIDER: S-EPMC8933873 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature