Darunavir

Manufactured by Selleck Chemicals

Darunavir is a type of laboratory equipment designed for use in chemical and pharmaceutical research. It is a protease inhibitor that functions by inhibiting the activity of the HIV-1 protease enzyme, which is essential for the replication of the HIV virus. The core function of Darunavir is to serve as a tool for researchers studying HIV and related diseases.

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3 protocols using darunavir

Reactivating HIV-1 Latency with Darunavir

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We used the Greene primary cell latency model, but substituted darunavir as the protease inhibitor⁵². Briefly, isolated CD4+ T cells (see primary cell isolation and culture) were infected with replication competent HIV-1 NL4–3 Luciferase virus (kind gift from Warner Greene) under spinoculation. Cells were then washed, incubated with 10 μM of the protease inhibitor darunavir (Selleckchem) for 48 h. darunavir is a more potent protease inhibitor and does not affect the cell latency model. Cell was washed again and a million cells incubated with various concentrations of compounds for 48 h in the presence of the integrase inhibitor raltegravir to prevent new integration events. Cells were then lysed and luciferase luminescence determined as a measure of viral reactivation from latency.

Albert B.J., Niu A., Ramani R., Marshall G.R., Wender P.A., Williams R.M., Ratner L., Barnes A.B, & Kyei G.B. (2017). Combinations of isoform-targeted histone deacetylase inhibitors and bryostatin analogues display remarkable potency to activate latent HIV without global T-cell activation. Scientific Reports, 7, 7456.

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Antiretroviral Compounds for Research

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Control compounds such as nevirapine (NVP), efavirenz (EFV), and azidothymidine (AZT) were obtained from the NIH AIDS Research and Reference Reagent Program. Raltegravir (RAL), dolutegravir (DTG), nevirapine (NVP), indinavir (IDV), AZT, ribavirin (RBV), lopinavir (LPV), darunavir (DRV), tenofovir (TFV), lamivudine (3TC), didanosine (ddI), emtricitabine (FTC), abacavir (ABC), efavirenz (EFV), etravirine (ETV), rilpivirine (RPV), and elvitegravir (EVG) were purchased from Selleck Chemicals.

Bonnard D., Le Rouzic E., Singer M.R., Yu Z., Le Strat F., Batisse C., Batisse J., Amadori C., Chasset S., Pye V.E., Emiliani S., Ledoussal B., Ruff M., Moreau F., Cherepanov P, & Benarous R. (2023). Biological and Structural Analyses of New Potent Allosteric Inhibitors of HIV-1 Integrase. Antimicrobial Agents and Chemotherapy, 67(7), e00462-23.

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Synthesis and Characterization of Anti-HIV Compounds

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The anti-HIV-1 reverse-transcriptase inhibitor EFdA/MK-8591/ISL was synthesized, as previously described (Nakata et al., 2007 (link)). The anti-HIV-1 protease inhibitor Darunavir (DRV) and the HIV-1 integrase inhibitor Dolutegravir (DTG) were purchased from Selleck (Houston, TX). PEP005 (PKC activator) was purchased from Cayman Chemical (Ann Arbor, MI); SAHA (vorinostat; HDAC inhibitor) from Santa Cruz Biotechnology (Dallas, TX); JQ-1 (BRD4 inhibitor) from BioVision (Milpitas, CA); GSK525762A (BRD4 inhibitor) from ChemScene (Monmouth Junction, NJ); Ro5-3335 from Merck (Darmstadt, Germany). Prostratin and Bryostatin-1 (PKC activator) were purchased from Sigma-Aldrich (St. Louis, MO), while Al-10-49 (CBFβ/RUNX inhibitor), Panobinostat (HDAC inhibitor), GS-9620 (TLR-7 agonist), and Birinapant (IAP inhibitor) were purchased from MedChem Express (Monmouth Junction, NJ). Phorbole 12-myristate13-acetate (PMA) and TNF-α were purchased from Wako Pure Chemical (Osaka, Japan) and BioLegend (San Diego, CA), respectively.

Matsuda K., Islam S., Takada T., Tsuchiya K., Yang Tan B.J., Hattori S.I., Katsuya H., Kitagawa K., Kim K.S., Matsuo M., Sugata K., Delino N.S., Gatanaga H., Yoshimura K., Matsushita S., Mitsuya H., Iwami S., Satou Y, & Maeda K. (2021). A widely distributed HIV-1 provirus elimination assay to evaluate latency-reversing agents in vitro. Cell Reports Methods, 1(8), 100122.

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