Article
Biochemistry & Molecular Biology
Sunday N. Okafor, Abigail Meyer, Jay Gadsden, Fadi Ahmed, Lilian Guzman, Hashim Ahmed, Jose A. Fernandez Romero, Pavimol Angsantikul
Summary: This study screened FDA-approved and investigational drugs for their potential as HIV-1 protease inhibitors. The findings revealed that CBR003PS and CBR013PS exhibited significant binding affinity to the HIV-1 protease with high stability, showing potential for repurposing as HIV-1 protease inhibitors.
Article
Infectious Diseases
Frank Mulindwa, Barbara Castelnuovo, Bruce Kirenga, Dennis Kalibbala, Priscilla Haguma, Martin Muddu, Fred C. Semitala
Summary: Despite the low utilization of double dose LPV/r in HIV patients on rifampicin-based TB treatment in Uganda's public HIV clinics, it does not seem to impact patient survival and viral suppression.
BMC INFECTIOUS DISEASES
(2021)
Article
Biochemistry & Molecular Biology
Roberto Arrigoni, Luigi Santacroce, Andrea Ballini, Luigi Leonardo Palese
Summary: The availability of drugs capable of blocking microorganism replication is a major accomplishment in medicine, but the increasing number of resistant strains poses a significant challenge for infectious disease treatment. Therefore, the search for new potential ligands for pathogens' life cycle is a crucial research area today.
Article
Chemistry, Medicinal
Gordon J. Lockbaum, Linah N. Rusere, Mina Henes, Klajdi Kosovrasti, Desaboini Nageswara Rao, Ean Spielvogel, Sook-Kyung Lee, Ellen A. Nalivaika, Ronald Swanstrom, Nese Kurt Yilmaz, Celia A. Schiffer, Akbar Ali
Summary: Protease inhibitors are powerful antivirals against HIV-1, but their effectiveness is reduced against resistant variants. Enhancing resistance profiles is crucial for developing more robust inhibitors, which could be promising for simplified next-generation antiretroviral therapies.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Virology
Irene T. Weber, Yuan-Fang Wang, Robert W. Harrison
Summary: The HIV protease is a key target for antiviral therapy, but drug resistance poses a growing threat. Dr. Stephen Oroszlan's contributions to understanding the function of the HIV protease and the development of clinical inhibitors are highlighted. Drug-resistant protease variants serve as valuable models for studying resistance mechanisms and evolution.
Article
Biochemistry & Molecular Biology
Sunday N. Okafor, Pavimol Angsantikul, Hashim Ahmed
Summary: This research utilized computational tools to screen a large compound library and identified potential HIV-1 protease inhibitors. Two optimized molecules showed promising activity and should be further investigated in vitro and in clinical trials.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Veronna Marie, Michelle Gordon
Summary: This study used molecular dynamics simulations to explore the co-evolutionary molecular mechanisms of resistance in HIV-1 PR and Gag, showing that resistance mutations in PR can alter drug binding and exacerbate binding when mutant PRs are bound to mutated Gag cleavage sites. The research also demonstrated that co-selection of mutations in both enzyme and substrate can lead to complex mechanisms of resistance, affecting the active site and flap flexibility in PR.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Multidisciplinary Sciences
Jeremie Prevost, Yaozong Chen, Fei Zhou, William D. Tolbert, Romain Gasser, Halima Medjahed, Manon Nayrac, Dung N. Nguyen, Suneetha Gottumukkala, Ann J. Hessell, Venigalla B. Rao, Edwin Pozharski, Rick K. Huang, Doreen Matthies, Andres Finzi, Marzena Pazgier
Summary: Resistance to the HIV-1 entry inhibitor temsavir is not solely determined by residue 375, but also involves other residues within the gp120 inner domain layers. The resistance is mediated by crosstalk between residue 375 and the inner domain layers. Additionally, temsavir has the ability to adjust its binding mode to accommodate changes in Env conformation, contributing to its broad antiviral activity.
NATURE COMMUNICATIONS
(2023)
Article
Public, Environmental & Occupational Health
Yiping Li, Qinjian Wang, Shu Liang, Chuanteng Feng, Hong Yang, Hang Yu, Dan Yuan, Shujuan Yang
Summary: This study found that a PI-based ART regimen is beneficial for reducing mortality in people living with HIV and HIV-1 drug resistance. Efforts should be made to detect HIV-1 drug resistance earlier and ensure timely adjustment to PI-based ART, maximizing the benefits of early switch treatment for these patients.
JMIR PUBLIC HEALTH AND SURVEILLANCE
(2022)
Article
Multidisciplinary Sciences
Ala M. Shaqra, Sarah N. Zvornicanin, Qiu Yu J. Huang, Gordon J. Lockbaum, Mark Knapp, Laura Tandeske, David T. Bakan, Julia Flynn, Daniel N. A. Bolon, Stephanie Moquin, Dustin Dovala, Nese Kurt Yilmaz, Celia A. Schiffer
Summary: The study determined the crystal structures of SARS-CoV-2 main protease (Mpro) bound to substrate peptides, defining the substrate envelope and identifying sites susceptible to drug resistance. These findings provide insights for developing robust inhibitors against SARS-CoV-2 and preventing drug resistance.
NATURE COMMUNICATIONS
(2022)
Review
Pharmacology & Pharmacy
Matthew Weichseldorfer, Marvin Reitz, Olga S. Latinovic
Summary: Combined antiretroviral therapy (cART) is widely recommended for controlling HIV-1 replication and improving the quality of life of infected individuals. However, latent infected cells remain a major barrier to treatment efficacy in the long term.
Review
Pharmacology & Pharmacy
Abdur Rauf, Anees Ahmed Khalil, Ahmed Olatunde, Muneeb Khan, Sirajudheen Anwar, Ahmed Alafnan, Kannan R. R. Rengasamy
Summary: Marine habitats are rich in diverse life forms that offer potential sources of novel bioactive compounds, including protease inhibitors with significant applications in pharmaceutical, nutraceutical, and cosmeceutical industries. Despite extensive research on protease inhibitors, many compounds have not advanced to clinical trials, highlighting the ongoing need for exploring new sources for their development.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Multidisciplinary Sciences
Huseyin Tunc, Berna Dogan, Busra Nur Darendeli Kiraz, Murat Sari, Serdar Durdagi, Seyfullah Kotil
Summary: The study aims to construct an artificial neural network model based on drug isolate fold (DIF) change to estimate the resistance potential of molecules inhibiting the HIV-1 protease (PR) enzyme. Machine learning models are used to accurately predict drug resistance and classify the inhibitors, which can help test the resistance of new drugs.
Article
Virology
Maria Kantzanou, Maria A. Karalexi, Anduela Zivinaki, Elena Riza, Helen Papachristou, Alexis Vasilakis, Christos Kontogiorgis, Athina Linos
Summary: This study compared the results of genotypic resistance derived from three interpretation algorithms in HIV-1 patients in Greece. It found discrepancies particularly in the classes of protease inhibitors and non-nucleoside reverse transcriptase inhibitors, underscoring the importance of matching results from different algorithms for optimized risk stratification.
JOURNAL OF CLINICAL VIROLOGY
(2021)
Article
Biology
Mehdi Yoosefian, Maryam Zeraati Moghani, Alfredo Juan
Summary: Researchers have discovered a new human immunodeficiency virus (HIV) protease inhibitor called ATV7 through molecular docking and molecular dynamics simulation, which has better antiviral effects and inhibitory ability than the existing drug atazanavir.
COMPUTERS IN BIOLOGY AND MEDICINE
(2022)
Article
Evolutionary Biology
Nevra Ozer, Aysegul Ozen, Celia A. Schiffer, Turkan Haliloglu
EVOLUTIONARY APPLICATIONS
(2015)
Article
Biochemistry & Molecular Biology
Sagar V. Kathuria, Yvonne H. Chan, R. Paul Nobrega, Ayseguel Ozen, C. Robert Matthews
Article
Oncology
Scott A. Foster, Daniel M. Whalen, Aysxeguel Oezen, Matthew J. Wongchenko, JianPing Yin, Ivana Yen, Gabriele Schaefer, John D. Mayfield, Juliann Chmielecki, Philip J. Stephens, Lee A. Albacker, Yibing Yan, Kyung Song, Georgia Hatzivassiliou, Charles Eigenbrot, Christine Yu, Andrey S. Shaw, Gerard Manning, Nicholas J. Skelton, Sarah G. Hymowitz, Shiva Malek
Article
Biochemistry & Molecular Biology
Nancy M. King, Moses Prabu-Jeyabalan, Rajintha M. Bandaranayake, Madhavi N. L. Nalam, Ellen A. Nalivaika, Aysegul Oezen, Turkan Haliloglu, Nese Kurt Yilmaz, Celia A. Schiffer
ACS CHEMICAL BIOLOGY
(2012)
Article
Biochemistry & Molecular Biology
Akbar Ali, Cihan Aydin, Reinhold Gildemeister, Keith P. Romano, Hong Cao, Ayseguel Oezen, Djade Soumana, Alicia Newton, Christos J. Petropoulos, Wei Huang, Celia A. Schiffer
ACS CHEMICAL BIOLOGY
(2013)
Article
Biochemistry & Molecular Biology
Sook-Kyung Lee, Marc Potempa, Madhavi Kolli, Aysegul Ozen, Celia A. Schiffer, Ronald Swanstrom
JOURNAL OF BIOLOGICAL CHEMISTRY
(2012)
Article
Chemistry, Physical
Ayseguel Oezen, Turkan Haliloglu, Celia A. Schiffer
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2012)
Article
Chemistry, Physical
Ayseguel Oezen, Woody Sherman, Celia A. Schiffer
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2013)
Article
Virology
Madhavi N. L. Nalam, Akbar Ali, Michael D. Altman, G. S. Kiran Kumar Reddy, Sripriya Chellappan, Visvaldas Kairys, Aysegul Ozen, Hong Cao, Michael K. Gilson, Bruce Tidor, Tariq M. Rana, Celia A. Schiffer
JOURNAL OF VIROLOGY
(2010)
Article
Multidisciplinary Sciences
Ayseguel Oezen, Kuan-Hung Lin, Nese Kurt Yilmaz, Celia A. Schiffer
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2014)
Review
Virology
Akbar Ali, Rajintha M. Bandaranayake, Yufeng Cai, Nancy M. King, Madhavi Kolli, Seema Mittal, Jennifer F. Murzycki, Madhavi N. L. Nalam, Ellen A. Nalivaika, Ayseguel Oezen, Moses M. Prabu-Jeyabalan, Kelly Thayer, Celia A. Schiffer
Article
Biophysics
Ayseguel Ozen, Mehmet Gonen, Ethem Alpaydin, Tuerkan Haliloglu
BMC STRUCTURAL BIOLOGY
(2009)
Article
Microbiology
Keith P. Romano, Akbar Ali, Cihan Aydin, Djade Soumana, Ayseguel Oezen, Laura M. Deveau, Casey Silver, Hong Cao, Alicia Newton, Christos J. Petropoulos, Wei Huang, Celia A. Schiffer
Article
Biochemistry & Molecular Biology
Ankita Chadda, Alexander G. Kozlov, Binh Nguyen, Timothy M. Lohman, Eric A. Galburt
Summary: In this study, it was found that the DNA damage response in Mycobacterium tuberculosis differs from well-studied model bacteria. The DNA repair helicase UvrD1 in Mtb is activated through a redox-dependent process and is closely associated with the homo-dimeric Ku protein. Additionally, Ku protein is shown to stimulate the helicase activity of UvrD1.
JOURNAL OF MOLECULAR BIOLOGY
(2024)