An HIV-1 integrase inhibitor
Bictegravir is an inhibitor of HIV-1 integrase (IC50 = 7.5 nM for strand transfer activity).1 It has antiviral activity against clinical isolates of HIV-1 in human peripheral blood mononuclear cells (PBMCs; EC50s = 0.04-1.7 nM). Bictegravir also inhibits HIV-1 viral infection in MT-2 and MT-4 cells, CD4+ T cells, and macrophages (EC50s = 1.5, 2.5, 1.5, and 6.6 nM, respectively) without exhibiting cytotoxicity (CC50s = 10.3, 3.7, 13, and 29.8 μM, respectively).
1.Tsiang, M., Jones, G.S., Goldsmith, J., et al.Antiviral activity of bictegravir (GS-9883), a novel potent HIV-1 integrase strand transfer inhibitor with an improved resistance profileAntimicrob. Agents Chemother.60(12)7086-7097(2016)
Cell experiment: | MT-2 cells are infected in bulk culture with HIV-1 IIIb at a cell density of 2×106 cells/mL for 3 h at 37°C. Infected MT-2 cells receive either DMSO (mock-treated control) or Bictegravir (BIC) at a final concentration greater than or equal to 20 times their respective antiviral 50% effective concentration (EC50). These plates are incubated at 37°C for either 12 h (for late reverse transcription product quantification) or 24 h (for 2-LTR circle and Alu-LTR product quantification), after which time the cells are harvested for total DNA isolation. DNA is extracted from each well using the DNA minikit and collected as a 100-μL eluate. TaqMan real-time PCR-quantified 2-LTR junctions (2-LTR circles), late reverse transcription products, and integration junctions (Alu-LTR) are normalized to the level of host globin gene in each sample[1]. |
参考文献: [1]. Tsiang M, et al. Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. Antimicrob Agents Chemother. 2016 Nov 21;60(12):7086-7097. | |
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