Bictegravir

Bictegravir is a novel, potent inhibitor of HIV-1 integrase with an IC50 of 7.5 nM.

Signaling Pathways >> Metabolic Enzyme/Protease >> HIV Integrase

Signaling Pathways >> Anti-infection >> HIV

Research Areas >> Infection

IC50: 7.5 nM (HIV-1 integrase)[1]

Bictegravir (BIC) inhibits the strand transfer activity with an IC50 of 7.5± 0.3 nM. Relative to its inhibition of strand transfer activity, Bictegravir is a much weaker inhibitor of 3′-processing activity of HIV-1 IN, with an IC50 of 241±51 nM. Bictegravir enhances the accumulation of 2-LTR circles ~5-fold relative to the mock-treated control and reduces the amount of authentic integration products in infected cells by 100-fold. Bictegravir potently inhibits HIV-1 replication in both MT-2 and MT-4 cells with EC50s of 1.5 and 2.4 nM, respectively. Bictegravir exhibits potent antiviral effects in both primary CD4+ T lymphocytes and monocyte-derived macrophages, with EC50s of 1.5±0.3 nM and 6.6±4.1 nM, respectively, which are comparable to values obtained in T-cell lines[1].

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].

[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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