Journal: Pharmaceuticals

Article Title: Development of Anti-HIV Therapeutics: From Conventional Drug Discovery to Cutting-Edge Technology

doi: 10.3390/ph17070887

Figure Lengend Snippet: List of FDA-approved HIV drugs by targets.

Article Snippet: 2005 , Aptivus , Tipranavir (TPV) , Small molecule , PR , Boehringer Ingelheim , PI.

Techniques:

Journal: eBioMedicine

Article Title: HIV protease inhibitor nelfinavir is a potent drug candidate against echinococcosis by targeting Ddi1-like protein

doi: 10.1016/j.ebiom.2022.104177

Figure Lengend Snippet: Nelfinavir inhibits the proteolysis activity of recombinant Emu Ddi1 . Emu Ddi1 was expressed in an E. coli system. Based on the amino acid compositions, this molecular weight of the recombinant protein was predicted to be appropriately 45 KD in the monomer (left) and 90 KD in the dimer (right) (a). At an optimum pH of 7.2, the recombinant Emu Ddi1 was able to hydrolyze the retro-pepsin substrate with a Km = 1.28 (95% CI: 0.80 to 2.02) μM and a Kcat = 0.36 s –1 (b). The HIVPIs, including lopinavir (LPV), indinavir (IDV), darunavir (DRV), fosamprenavir (FAPV), ritonavir (RTV), tipranavir (TPV), atazanavir (ATV), amprenavir (APV), nelfinavir (NFV) and saquinavir (SQV) were tested (n = 3). The enzyme activity of this recombinant protein (at 0.5 μM) could be apparently blocked by nelfinavir (NFV) and saquinavir (SQV) (40 μM) (c). The half-maximal inhibitory concentration (IC 50 ) of nelfinavir on the recombinant Emu Ddi1 was 45.95 μM (d). The results shown are representative of two or more independent experiments. Data shown are represented as mean ± SD.

Article Snippet: HIV protease inhibitors (HIVPIs), including nelfinavir (NFV, CAS NO. 159989-64-7), lopinavir (LPV, CAS NO. 192725-17-0), indinavir (IDV, CAS NO.180686-37-8), darunavir (DRV, CAS NO. 206361-99-1), fosamprenavir (FAPV, CAS NO. 226700-79-4), ritonavir (RTV, CAS NO. 176655-55-3), tipranavir (TPV, CAS NO. 174484-41-4), atazanavir (ATV, CAS NO. 198904-31-3), saquinavir (SQV, CAS NO. 149845-06-7), and amprenavir (APV, CAS NO. 161814-49-9), were purchased from Macklin (Shanghai, China).

Techniques: Activity Assay, Recombinant, Molecular Weight, Concentration Assay

Journal: Antimicrobial Agents and Chemotherapy

Article Title: Novel Protease Inhibitors Containing C-5-Modified bis -Tetrahydrofuranylurethane and Aminobenzothiazole as P2 and P2′ Ligands That Exert Potent Antiviral Activity against Highly Multidrug-Resistant HIV-1 with a High Genetic Barrier against the Emergence of Drug Resistance

doi: 10.1128/AAC.00372-19

Figure Lengend Snippet: Thermal stability of wild-type HIV-1 protease (PRWT) and lysozyme in the presence and absence of each compound using differential scanning fluorimetry (DSF). The relative fluorescence intensity was plotted at each temperature. Melting temperature (Tm) values were calculated from the top of the peak in the derivative plot. (A) Melting curves of PRWT in the presence and absence of selected FDA-approved PIs. Thermal stability curves with all the compounds shifted to higher temperatures than in the absence of each compound with Tm values ranging from 75.42 (amprenavir [APV]) to 83.08°C (tipranavir [TPV]), with a ΔTm value of 19.24°C to 26.90°C. (B) Melting curves of PRWT in the presence and absence of GRL-057-14, GRL-058-14, and GRL-059-14. The curve of DRV is shown as a reference. All three compounds significantly shifted the thermal stability curves to higher temperatures than in the absence of each compound. Their Tm values were much higher than those of all the FDA-approved PIs tested (A). (C) Melting curves of lysozyme in the presence and absence of GRL-057-14, GRL-058-14, GRL-059-14, and DRV. None of the PIs examined affected the thermal stability curves, indicating that all the PIs examined were highly specific to PRWT and had no significant interactions with lysozyme.

Article Snippet: Indinavir sulfate (IDV) and tipranavir (TPV) were purchased from United States Biological (Swampscott, MA).

Techniques: Fluorescence