HIV-1 protease inhibitors with a P1 phosphonate modification maintain potency against drug-resistant variants by increased interactions with flap residues.

[1]  H. Günthard,et al.  Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2022 Recommendations of the International Antiviral Society-USA Panel. , 2022, JAMA.

[2]  Arun K. Ghosh,et al.  Beyond darunavir: recent development of next generation HIV-1 protease inhibitors to combat drug resistance. , 2022, Chemical communications.

[3]  L. Hui,et al.  Effectiveness and Safety Analysis of PIs/r Based Dual Therapy in Treatment-Naïve, HIV/AIDS Patients: A Network Meta Analysis of Randomized Controlled Trials , 2022, Frontiers in Pharmacology.

[4]  C. Schiffer,et al.  Inhibiting HTLV-1 Protease: A Viable Antiviral Target. , 2021, ACS chemical biology.

[5]  C. Schiffer,et al.  Drug Design Strategies to Avoid Resistance in Direct-Acting Antivirals and Beyond. , 2021, Chemical reviews.

[6]  C. Schiffer,et al.  Structural Analysis of Potent Hybrid HIV-1 Protease Inhibitors Containing Bis-Tetrahydrofuran in a Pseudo-Symmetric Dipeptide Isostere. , 2020, Journal of medicinal chemistry.

[7]  Arun K. Ghosh,et al.  Structure-Based Design of Highly Potent HIV-1 Protease Inhibitors Containing New Tricyclic Ring P2-Ligands: Design, Synthesis, Biological, and X-ray Structural Studies. , 2020, Journal of medicinal chemistry.

[8]  E. Negredo,et al.  Maintenance of virologic suppression and improvement in comorbidities after simplification to raltegravir plus boosted darunavir among treatment-experienced HIV-infected patients , 2020, International journal of STD & AIDS.

[9]  R. Maserati,et al.  96-week results of a dual therapy with darunavir/ritonavir plus rilpivirine once a day vs triple therapy in patients with suppressed viraemia: virological success and non-HIV related morbidity evaluation , 2020, HIV research & clinical practice.

[10]  Shuntai Zhou,et al.  Selection of HIV-1 for resistance to fifth-generation protease inhibitors reveals two independent pathways to high-level resistance , 2019, bioRxiv.

[11]  Nese Kurt Yilmaz,et al.  HIV-1 Protease Inhibitors Incorporating Stereochemically Defined P2' Ligands to Optimize Hydrogen Bonding in the Substrate Envelope. , 2019, Journal of medicinal chemistry.

[12]  Shuntai Zhou,et al.  pM to µM - Elucidating the Role of Distal Mutations in HIV-1 Protease in Conferring Drug Resistance. , 2019, ACS chemical biology.

[13]  C. Schiffer,et al.  Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. , 2018, ACS infectious diseases.

[14]  Arun K. Ghosh,et al.  Design and Synthesis of Highly Potent HIV-1 Protease Inhibitors Containing Tricyclic Fused Ring Systems as Novel P2 Ligands: Structure-Activity Studies, Biological and X-ray Structural Analysis. , 2018, Journal of medicinal chemistry.

[15]  Arun K. Ghosh,et al.  Design of Highly Potent, Dual‐Acting and Central‐Nervous‐System‐Penetrating HIV‐1 Protease Inhibitors with Excellent Potency against Multidrug‐Resistant HIV‐1 Variants , 2018, ChemMedChem.

[16]  Arun K. Ghosh,et al.  A novel central nervous system-penetrating protease inhibitor overcomes human immunodeficiency virus 1 resistance with unprecedented aM to pM potency , 2017, eLife.

[17]  C. Schiffer,et al.  Elucidating the Interdependence of Drug Resistance from Combinations of Mutations. , 2017, Journal of chemical theory and computation.

[18]  Wei Huang,et al.  Hepatitis C Virus NS3/4A Protease Inhibitors Incorporating Flexible P2 Quinoxalines Target Drug Resistant Viral Variants. , 2017, Journal of medicinal chemistry.

[19]  Irene T Weber,et al.  Design and Development of Highly Potent HIV-1 Protease Inhibitors with a Crown-Like Oxotricyclic Core as the P2-Ligand To Combat Multidrug-Resistant HIV Variants. , 2017, Journal of medicinal chemistry.

[20]  A. Antinori,et al.  Week 96 efficacy and safety of darunavir/ritonavir monotherapy vs. darunavir/ritonavir with two nucleoside reverse transcriptase inhibitors in the PROTEA trial , 2017, HIV medicine.

[21]  T. Cihlar,et al.  Current status and prospects of HIV treatment. , 2016, Current opinion in virology.

[22]  Peng Zhan,et al.  Anti-HIV Drug Discovery and Development: Current Innovations and Future Trends. , 2016, Journal of medicinal chemistry.

[23]  Arun K. Ghosh,et al.  Recent Progress in the Development of HIV-1 Protease Inhibitors for the Treatment of HIV/AIDS. , 2016, Journal of medicinal chemistry.

[24]  Jennifer L. Knight,et al.  OPLS3: A Force Field Providing Broad Coverage of Drug-like Small Molecules and Proteins. , 2016, Journal of chemical theory and computation.

[25]  R. Raines,et al.  Fluorogenic Assay for Inhibitors of HIV-1 Protease with Sub-picomolar Affinity , 2015, Scientific Reports.

[26]  C. Schiffer,et al.  Structural basis and distal effects of Gag substrate coevolution in drug resistance to HIV-1 protease , 2014, Proceedings of the National Academy of Sciences.

[27]  Hong Cao,et al.  Substrate envelope-designed potent HIV-1 protease inhibitors to avoid drug resistance. , 2013, Chemistry & biology.

[28]  William A. Lee,et al.  Discovery of GS-8374, a potent human immunodeficiency virus type 1 protease inhibitor with a superior resistance profile , 2011 .

[29]  William A. Lee,et al.  In Vitro Characterization of GS-8374, a Novel Phosphonate-Containing Inhibitor of HIV-1 Protease with a Favorable Resistance Profile , 2011, Antimicrobial Agents and Chemotherapy.

[30]  Michael K. Gilson,et al.  Evaluating the Substrate-Envelope Hypothesis: Structural Analysis of Novel HIV-1 Protease Inhibitors Designed To Be Robust against Drug Resistance , 2010, Journal of Virology.

[31]  Randy J. Read,et al.  Acta Crystallographica Section D Biological , 2003 .

[32]  Paul D Adams,et al.  Electronic Reprint Biological Crystallography Electronic Ligand Builder and Optimization Workbench (elbow ): a Tool for Ligand Coordinate and Restraint Generation Biological Crystallography Electronic Ligand Builder and Optimization Workbench (elbow): a Tool for Ligand Coordinate and Restraint Gener , 2022 .

[33]  R. Swanstrom,et al.  A Strongly Transdominant Mutation in the Human Immunodeficiency Virus Type 1 gag Gene Defines an Achilles Heel in the Virus Life Cycle , 2009, Journal of Virology.

[34]  Lin Shen,et al.  Dose-response curve slope sets class-specific limits on inhibitory potential of anti-HIV drugs , 2008, Nature Medicine.

[35]  M. Hanlon,et al.  In Vitro Antiviral Activity of the Novel, Tyrosyl-Based Human Immunodeficiency Virus (HIV) Type 1 Protease Inhibitor Brecanavir (GW640385) in Combination with Other Antiretrovirals and against a Panel of Protease Inhibitor-Resistant HIV , 2007, Antimicrobial Agents and Chemotherapy.

[36]  Randy J. Read,et al.  Phaser crystallographic software , 2007, Journal of applied crystallography.

[37]  Jack Snoeyink,et al.  Nucleic Acids Research Advance Access published April 22, 2007 MolProbity: all-atom contacts and structure validation for proteins and nucleic acids , 2007 .

[38]  Irene T Weber,et al.  A Novel Bis-Tetrahydrofuranylurethane-Containing Nonpeptidic Protease Inhibitor (PI), GRL-98065, Is Potent against Multiple-PI-Resistant Human Immunodeficiency Virus In Vitro , 2007, Antimicrobial Agents and Chemotherapy.

[39]  William A. Lee,et al.  Suppression of HIV-1 protease inhibitor resistance by phosphonate-mediated solvent anchoring. , 2006, Journal of molecular biology.

[40]  M. Hanlon,et al.  Ultra-potent P1 modified arylsulfonamide HIV protease inhibitors: the discovery of GW0385. , 2006, Bioorganic & medicinal chemistry letters.

[41]  Celia A Schiffer,et al.  Discovery and selection of TMC114, a next generation HIV-1 protease inhibitor. , 2005, Journal of medicinal chemistry.

[42]  Celia A Schiffer,et al.  Design of HIV-1 protease inhibitors active on multidrug-resistant virus. , 2005, Journal of medicinal chemistry.

[43]  Kevin Cowtan,et al.  research papers Acta Crystallographica Section D Biological , 2005 .

[44]  Celia A Schiffer,et al.  Combating susceptibility to drug resistance: lessons from HIV-1 protease. , 2004, Chemistry & biology.

[45]  J. Kappes,et al.  Emergence of Resistant Human Immunodeficiency Virus Type 1 in Patients Receiving Fusion Inhibitor (T-20) Monotherapy , 2002, Antimicrobial Agents and Chemotherapy.

[46]  Celia A Schiffer,et al.  Lack of synergy for inhibitors targeting a multi‐drug‐resistant HIV‐1 protease , 2002, Protein science : a publication of the Protein Society.

[47]  C. Craik,et al.  Regulation of autoproteolysis of the HIV-1 and HIV-2 proteases with engineered amino acid substitutions. , 1993, The Journal of biological chemistry.

[48]  D. P. Brunner,et al.  Large scale purification and refolding of HIV-1 protease fromEscherichia coli inclusion bodies , 1993, Journal of protein chemistry.

[49]  L J Davis,et al.  Active human immunodeficiency virus protease is required for viral infectivity. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[50]  Irene T Weber,et al.  Design of HIV protease inhibitors targeting protein backbone: an effective strategy for combating drug resistance. , 2008, Accounts of chemical research.

[51]  Z. Otwinowski,et al.  [20] Processing of X-ray diffraction data collected in oscillation mode. , 1997, Methods in enzymology.

[52]  A. Brünger.  Free R value: a novel statistical quantity for assessing the accuracy of crystal structures , 1992, Nature.