Potent antiviral HIV-1 protease inhibitor combats highly drug resistant mutant PR20
Journal Article
·
· Biochemical and Biophysical Research Communications
- Georgia State Univ., Atlanta, GA (United States)
- Purdue Univ., West Lafayette, IN (United States)
Drug-resistance threatens effective treatment of HIV/AIDS. Clinical inhibitors, including darunavir (1), are ineffective for highly resistant protease mutant PR20, however, here antiviral compound 2 derived from 1 with fused tricyclic group at P2, extended amino-benzothiazole P2’ ligand and two fluorine atoms on P1 shows 16-fold better inhibition of PR20 enzyme activity. Crystal structures of PR20 and wild-type PR complexes reveal how the extra groups of 2 counteract the expanded ligand-binding pocket, dynamic flaps, and faster dimer dissociation of PR20.
- Research Organization:
- Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Sponsoring Organization:
- National Institutes of Health (NIH); USDOE Office of Science (SC), Basic Energy Sciences (BES)
- Grant/Contract Number:
- W-31109-ENG-38
- OSTI ID:
- 1572565
- Alternate ID(s):
- OSTI ID: 1703108
- Journal Information:
- Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 1 Vol. 519; ISSN 0006-291X
- Publisher:
- ElsevierCopyright Statement
- Country of Publication:
- United States
- Language:
- ENGLISH
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