FLS-359, a selective and orally active allosteric modulator for sirtuin 2, has an IC50 of 3 μM. It displays antiviral activity against both RNA and DNA viruses by inhibiting DNA/RNA replication [1].

SIRT2:3 μM

FLS-359 (0-100 μM) inhibits the deacetylation of histone H3 by SIRT2, demonstrating substrate selectivity [1]. It suppresses the growth of various RNA and DNA viruses, including SARS-CoV-2, influenza A, hepatitis B, and respiratory syncytial virus, with an IC50 range of 0.3-6.7 μM [1]. FLS-359 (0-10 μM, 24 h) hinders lytic activation of the Epstein-Barr virus (EBV) in Akata cells and the spread of human cytomegalovirus (HCMV) in diploid fibroblasts (IC50 0.466 μM) [1]. FLS-359 (0-5 μM, 72 h) also reduces intracellular viral nucleic acid accumulation, extracellular viral particle production, and the infectivity of viral particles [1].

Administered orally at a dose of 50 mg/kg, FLS-359 demonstrates good plasma exposure, with a half-life of 6 hours, C_max of 89 μM, and an AUC of 713 μM•h/mL [1]. When given at the same dose twice daily for 11 days, FLS-359 inhibits human cytomegalovirus (HCMV) infection in immunodeficient mice [1]. Animal models used include the mouse gelfoam-fibroblast model and the human lung-only mouse model [1].