BPR3P0128, a non-nucleoside RNA-dependent RNA polymerase (RdRp) inhibitor, is effective orally and can inhibit various SARS-CoV-2 variants. It exhibits EC 50 values of 0.62 µM for SARS-CoV-2 and 0.14 µM for HCoV-229E, demonstrating potent anti-pancoronavirus activity at submicromolar concentrations. Additionally, BPR3P0128 displays synergistic antiviral effects when used in combination with Remdesivir [1].

BPR3P0128, at a concentration of 10 μM over 24 hours, effectively inhibits the replication of SARS-CoV-2 and reduces cytokine expression caused by the virus in the human lung cancer cell line Calu-3 [1]. The compound demonstrates comprehensive activity against coronavirus by effectively inhibiting various SARS-CoV-2 variants, including α, β, γ, δ, and Omicron strains at concentrations of 1 μM and 10 μM [1]. When combined with Remdesivir (4 μM and 8 μM), BPR3P0128 (1 μM and 2 μM; 24 hours) exhibits synergistic antiviral activity [1]. In Vero E6 cells containing SARS-CoV-2 virus, concentrations of 10 μM significantly decreased the mRNA levels of CXCL10, IL-6, TNF-α, and INF-β as per RT-PCR analysis [1]. In Western Blot Analysis, BPR3P0128 and Remdesivir together more significantly inhibited NP expression in the same cell line [1]. Additionally, in a HEK293T cell-based RdRp reporter model, BPR3P0128 at concentrations of 0.1 μM, 1 μM, and 10 μM, alongside Remdesivir (1 μM, 10 μM, 100 μM), inhibited the activity of SARS-CoV-2 RdRp without reducing the expression level of nsp12 [1].

Pharmacokinetic analysis: [1] Route Dose (mg/kg) Cl (mL·min/kg) t 1/2 (h) F (%) i.v. 0.01 1.3 / / p.o. 0.01 / 8.1 78.7%