Article
Cell Biology
Anne Monette, Meijuan Niu, Maya Nijhoff Asser, Robert J. Gorelick, Andrew J. Mouland
Summary: This study reveals that HIV-1 core proteins can condense with viral genomic RNA to form membraneless biomolecular condensates (BMCs), and investigates the characteristics and drug sensitivity of these BMCs in living cells. The findings demonstrate that HIV-1 core BMCs exhibit similar features to other biomolecular condensates and can be further formed into visible condensates through protease-mediated maturation, playing a crucial role in the viral ingress process.
Article
Biochemical Research Methods
Karina Pikalyova, Alexey Orlov, Arkadii Lin, Olga Tarasova, Marcou Gilles, Dragos Horvath, Vladimir Poroikov, Alexandre Varnek
Summary: A new methodology based on generative topographic mapping (GTM) was introduced for predicting the drug resistance of HIV strains. The approach combines high accuracy and interpretability, allowing for visualization and analysis of sequence space and treatment optimization. Several case studies demonstrate the practicality of this method.
Article
Chemistry, Medicinal
Giavana R. Prucha, Sean Henry, Klarissa Hollander, Zachary J. Carter, Krasimir A. Spasov, William L. Jorgensen, Karen S. Anderson
Summary: This study reports the synthesis of 34 compounds that covalently inhibit reverse transcriptase to overcome the issue of resistance to non-nucleoside reverse transcriptase inhibitors. Two of these inhibitors demonstrate biochemical, structural, enzyme kinetic, mass spectrometry, and antiviral activity against HIV-1.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Xiangyi Jiang, Boshi Huang, Waleed A. Zalloum, Chin-Ho Chen, Xiangkai Ji, Zhen Gao, Jiaojiao Dai, Minghui Xie, Dongwei Kang, Erik De Clercq, Christophe Pannecouque, Xinyong Liu, Peng Zhan
Summary: Novel diarypyrimidine derivatives were designed based on previously reported HIV-1 NNRTIs BH-11c and XJ-10c to improve antiresistance and drug-like profiles. Compound 12g showed the highest inhibitory activity against wild-type and NNRTI-resistant HIV-1 strains, with EC50 values ranging from 0.024 to 0.0010 μM. Its improved antiresistance profile compared to ETR was explained by MD simulation study and it also showed improved water solubility and other drug-like properties. Compound 12g exhibited promising pharmacokinetics parameters and could be a potential lead compound for new antiretroviral drug development.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Cell Biology
Carl J. Balibar, Daniel J. Klein, Beata Zamlynny, Tracy L. Diamond, Zhiyu Fang, Carol A. Cheney, Jan Kristoff, Meiqing Lu, Marina Bukhtiyarova, Yangsi Ou, Min Xu, Lei Ba, Steven S. Carroll, Abdellatif El Marrouni, John F. Fay, Ashley Forster, Shih Lin Goh, Meigang Gu, Daniel Krosky, Daniel I. S. Rosenbloom, Payal Sheth, Deping Wang, Guoxin Wu, Matthias Zebisch, Tian Zhao, Paul Zuck, Jay Grobler, Daria J. Hazuda, Bonnie J. Howell, Antonella Converso
Summary: Antiretroviral therapy can inhibit HIV-1 replication but cannot cure the infection due to the persistence of a reservoir in the host genome. Reduction of this reservoir is important for HIV-1 cure. Some nonnucleoside reverse transcriptase inhibitors have shown selective cytotoxicity against HIV-1 in vitro, but their concentrations required are much higher than approved dosages. By focusing on this secondary activity, researchers have discovered bifunctional compounds called targeted activators of cell kill (TACK) that can kill HIV-1-infected cells at clinically achievable concentrations. These TACK molecules bind to the reverse transcriptase-p66 domain of monomeric Gag-Pol and act as allosteric modulators, promoting dimerization and premature intracellular viral protease activation, leading to death of HIV-1(+) cells. TACK molecules retain potent antiviral activity and selectively eliminate infected CD4(+) T cells, providing a potential immune-independent clearance strategy.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Virology
Maria E. Cilento, Xin Wen, Aaron B. Reeve, Obiaara B. Ukah, Alexa A. Snyder, Ciro M. Carrillo, Cole P. Smith, Kristin Edwards, Claudia C. Wahoski, Deborah R. Kitzler, Eiichi N. Kodama, Hiroaki Mitsuya, Michael A. Parniak, Philip R. Tedbury, Stefan G. Sarafianos
Summary: TDF and ISL are highly potent nucleoside reverse transcriptase inhibitors with different resistance profiles. This study found that ISL is sensitive to the K65R mutation, while TDF is sensitive to the M184V mutation. The sensitivity to these drugs also varies among different HIV subtypes, and the S68G polymorphism may enhance the fitness of drug-resistant mutants in certain genetic backgrounds.
Article
Virology
Shih-Han Hsieh, Fu-Hsien Yu, Kuo-Jung Huang, Chin-Tien Wang
Summary: RT modulates PR activation by affecting Gag-Pol/Gag-Pol interaction. Amino acid substitutions in RT destabilize RT and make it susceptible to PR degradation. LRM mutants exhibit reduced Gag cleavage efficiencies and attenuate the enhancing effect of EFV on Gag cleavage.
JOURNAL OF VIROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Mahta Mansouri, Shawn Rumrill, Shane Dawson, Adam Johnson, Jo-Anne Pinson, Menachem J. Gunzburg, Catherine F. Latham, Nicholas Barlow, George W. Mbogo, Paula Ellenberg, Stephen J. Headey, Nicolas Sluis-Cremer, David Tyssen, Joseph D. Bauman, Francesc X. Ruiz, Eddy Arnold, David K. Chalmers, Gilda Tachedjian
Summary: Human immunodeficiency virus type I (HIV-1) is a major global health burden, and the emergence of drug-resistance mutations necessitates the development of novel drugs. In this study, a fragment-based drug discovery approach was used to optimize a hit fragment (compound B-1) that targets the viral protein reverse transcriptase (RT) in a novel site. Different compound series were synthesized and evaluated for their RT binding and inhibition, leading to the identification of a lead compound with promising inhibitory activity. This study offers a starting point for the development of novel dual inhibitors targeting the NNRTI-binding pocket and an adjacent site.
Article
Infectious Diseases
Francesco Saladini, Federica Giammarino, Behnaz A. Hosseini, Alessia Giannini, Adele Boccuto, Filippo Dragoni, Ilaria Vicenti, Robert W. Shafer, Maurizio Zazzi
Summary: In this study, cross-resistance to doravirine was observed in NNRTI-resistant viruses with complex mutational patterns, even in the absence of major IAS-USA doravirine RAMs. Therefore, doravirine resistance may be underestimated in viruses with multiple NNRTI mutations based on the simple IAS-USA reference list. The fold change values correlated well with predicted susceptibility as inferred by Stanford HIV Drug Resistance Database and ANRS algorithms.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2021)
Article
Chemistry, Medicinal
Huiyan Lu, Yuji Komukai, Koto Usami, Yan Guo, Xinyue Qiao, Michiyoshi Nukaga, Tyuji Hoshino
Summary: Chemotherapy for human immunodeficiency virus type-1 (HIV-1) has made significant progress, although the emergence of drug-resistant variants remains a serious problem. This study obtained the binding structures of six inhibitory compounds with a recombinant protein of the HIV-1 RNase H domain using X-ray crystal analysis. The compounds were found to bind to the catalytic site and coordinate with two divalent metal ions. These findings provide a solid foundation for developing potent inhibitors for HIV-1 RNase H activity.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Chemistry, Medicinal
Xu Ling, Qing-Qing Hao, Christophe Pannecouque, Erik De Clercq, Fen-Er Chen
Summary: This paper reports a study on a novel class of HIV-1 reverse transcriptase inhibitors. By synthesizing 39 derivatives, it was found that these compounds exhibited good inhibitory activity against wild-type and resistant mutant viruses, especially the rilpivirine-associated resistant mutant E138K. Molecular docking analysis provided insights into the biological activity of these compounds and identified potential drug candidates.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Yali Sang, Christophe Pannecouque, Erik De Clercq, Chunlin Zhuang, Fener Chen
Summary: Fifteen naphthyl-carboxamide-DAPYs were generated to explore chemical space in reverse transcriptase (RT) binding site via lead optimization strategy. They displayed high inhibitory activity against wildtype (WT) and rilpivirine-associated resistant mutant E138K viruses, with compound a1 showing exceptionally inhibitory effects. Molecular docking analysis elucidated the biological activity and offered a structural insight for follow-up research.
BIOORGANIC CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Takumi Yasuno, Tomoyuki Ohe, Hiroki Kataoka, Kosho Hashimoto, Yumiko Ishikawa, Keigo Furukawa, Yasuhiro Tateishi, Toi Kobayashi, Kyoko Takahashi, Shigeo Nakamura, Tadahiko Mashino
Summary: In this study, three novel fullerene derivatives were synthesized, with certain compounds exhibiting inhibitory activity against HIV reverse transcriptase and HIV protease in the low micromolar range. The derivatives with a specific alkyl chain showed more potent inhibition of HIV-PR, suggesting a potential strategy for enhancing HIV-PR inhibitory activity.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Multidisciplinary Sciences
Radhika Biyani, Kirti Sharma, Kenji Kojima, Madhu Biyani, Vishnu Sharma, Tarun Kumawat, Kevin Maafu Juma, Itaru Yanagihara, Shinsuke Fujiwara, Eiichi Kodama, Yuzuru Takamura, Masahiro Takagi, Kiyoshi Yasukawa, Manish Biyani
Summary: This new isothermal nucleic acid amplification assay, called RICCA, allows for rapid and direct detection of viruses with low viral loads. It has shown high sensitivity in detecting RNA viruses directly from saliva samples and synthetic templates of SARS-CoV-2. The assay can be used in real-time point-of-care testing and has a total assay time of 15-30 minutes for detecting heat-inactivated SARS-CoV-2 virus in human saliva.
SCIENTIFIC REPORTS
(2021)
Article
Infectious Diseases
Mijael Rozenszajn, Solange Arazi-Caillaud, Moira Taicz, Rosa Bologna, Andrea Mangano, Paula C. Aulicino
Summary: Baseline genotyping for HIV-1 in vertically infected children is crucial for personalized medicine. Children with PDR require closer monitoring of their first-line ART regimens to prevent early virological failure and resistance accumulation.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2022)
Article
Allergy
Hille Suojalehto, Katri Suuronen, Paul Cullinan, Irmeli Lindstrom, Joaquin Sastre, Jolanta Walusiak-Skorupa, Xavier Munoz, Donatella Talini, Pavlina Klusackova, Vicky Moore, Rolf Merget, Cecilie Svanes, Paola Mason, Marco Dell'Omo, Gianna Moscato, Santiago Quirce, Jennifer Hoyle, David Sherson, Alexandra Preisser, Martin Seed, Catherine Rifflart, Julien Godet, Frederic de Blay, Olivier Vandenplas
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE
(2020)
Article
Allergy
Manon Grandbastien, Anays Piotin, Julien Godet, Ines Abessolo-Amougou, Carole Ederle, Irina Enache, Philippe Fraisse, Thi Cam Tu Hoang, Loic Kassegne, Aissam Labani, Pierre Leyendecker, Louise Manien, Christophe Marcot, Guillaume Pamart, Benjamin Renaud-Picard, Marianne Riou, Virginie Doyen, Romain Kessler, Samira Fafi-Kremer, Carine Metz-Favre, Naji Khayath, Frederic de Blay
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE
(2020)
Article
Multidisciplinary Sciences
Hanna Manko, Vincent Normant, Quentin Perraud, Tania Steffan, Veronique Gasser, Emmanuel Boutant, Eleonore Real, Isabelle J. Schalk, Yves Mely, Julien Godet
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2020)
Article
Allergy
Marta Wiszniewska, Perrine Dellis, Vera van Kampen, Hille Suojalehto, Xavier Munoz, Jolanta Walusiak-Skorupa, Irmeli Lindstrom, Rolph Merget, Christian Romero-Mesones, Joaquin Sastre, Santiago Quirce, Paola Mason, Catherine Rifflart, Julien Godet, Frederic de Blay, Olivier Vandenplas
Summary: This study emphasizes the importance of induced sputum analysis in investigating work-related asthma symptoms to identify isolated increases in sputum eosinophils consistent with a diagnosis of OEB.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE
(2021)
Article
Critical Care Medicine
Charles Tacquard, Alexandre Mansour, Alexandre Godon, Julien Godet, Julien Poissy, Delphine Garrigue, Eric Kipnis, Sophie Rym Hamada, Paul Michel Mertes, Annick Steib, Mathilde Ulliel-Roche, Belaid Bouhemad, Maxime Nguyen, Florian Reizine, Isabelle Gouin-Thibault, Marie Charlotte Besse, Nived Collercandy, Stefan Mankikian, Jerrold H. Levy, Yves Gruel, Pierre Albaladejo, Sophie Susen, Anne Godier
Summary: High-dose prophylactic anticoagulation is associated with a reduced risk of thrombotic complications in critically ill patients with COVID-19 without increasing the risk of bleeding. Further randomized controlled trials comparing prophylaxis with higher doses of anticoagulants are needed to confirm these results.
Article
Anatomy & Morphology
Yann Philippe Charles, Yves Ntilikina, Arnaud Collinet, Sebastien Schuller, Julien Garnon, Julien Godet, Philippe Clavert
Summary: The accuracy of percutaneous pedicle screw placement is lower in the cranial thoracic spine, with higher rates of malposition and significant risk compared to the caudal thoracic and lumbosacral spine. Below T7, this method appears safe and reliable for instrumentation.
SURGICAL AND RADIOLOGIC ANATOMY
(2021)
Article
Allergy
Nicolas Migueres, Charlotte Debaille, Jolanta Walusiak-Skorupa, Agnieszka Lipinska-Ojrzanowska, Xavier Munoz, Vera van Kampen, Hille Suojalehto, Katri Suuronen, Martin Seed, Sewon Lee, Catherine Rifflart, Julien Godet, Frederic de Blay, Olivier Vandenplas
Summary: This study found that QAC-induced OA is associated with a highly eosinophilic pattern of airway response and provides further evidence supporting the sensitizing potential of QACs. The findings highlight the heterogeneous nature of the pathobiologic pathways involved in OA caused by LMW agents.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE
(2021)
Article
Allergy
Anays Piotin, Julien Godet, Jason A. Trubiano, Manon Grandbastien, Lydie Guenard-Bilbault, Frederic de Blay, Carine Metz-Favre
Summary: The study validated the PEN-FAST clinical decision rule in a population with high risk of suspected immediate amoxicillin allergy, showing good discrimination in identifying low-risk penicillin allergies and revealing clinical predictive factors of amoxicillin immediate hypersensitivity.
ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY
(2022)
Article
Obstetrics & Gynecology
Floriane Jochum, Olivier Garbin, Julien Godet, Mathilde Ragueneau, Chantal Meyer, Sylvie Billecocq, Lise Lecointre, Cherif Akladios, Aline Host
Summary: This study evaluated the changes in quality of life in patients with stress urinary incontinence using the connected biofeedback EMY Kegel trainer. The results demonstrated that using the EMY Kegel trainer can improve quality of life and urinary symptoms.
JOURNAL OF GYNECOLOGY OBSTETRICS AND HUMAN REPRODUCTION
(2022)
Article
Medicine, General & Internal
Sabrina Kepka, Francois Lersy, Julien Godet, Frederic Blanc, Mathias Bilger, Anne Botzung, Catherine Kleitz, Jeanne Merignac, Emmanuel Ohrant, Franck Garnier, Francois Pietra, Vincent Noblet, Caroline Deck, Remy Willinger, Stephane Kremer
Summary: This study aims to evaluate the MRI and neuropsychological abnormalities in professional retired soccer players exposed to subconcussive impacts compared to athletes who are not exposed to head impacts. By using advanced MRI techniques and neuropsychological tests, the researchers hope to uncover the long-term effects of repetitive subconcussive impacts on soccer players.
Article
Chemistry, Multidisciplinary
Hanna Manko, Yves Mely, Julien Godet
Summary: Spectrally-resolved single molecule localization microscopy (srSMLM) is enhanced by a deep-learning image processing routine called srUnet, which compensates for the resolution loss in simultaneously recording spectra and localization information. srUnet significantly improves both localization and spectral precision, especially for low-emitting species. It increases the fraction of localizations that can be characterized spatially and spectrally and preserves spectral shifts and linearity. srUnet greatly facilitates wavelength assignment in multicolor experiments and has the potential to make srSMLM the new standard for multicolor single molecule imaging.
Article
Radiology, Nuclear Medicine & Medical Imaging
Sabrina Kepka, Kevin Zarca, Francois Lersy, Mylene Moris, Julien Godet, Jeanne Deur, Marie Stoessel, Joris Muller, Pierrick Le Borgne, Seyyid Baloglu, Marie Celine Fleury, Mathieu Anheim, Pascal Bilbault, Guillaume Bierry, Isabelle Durand Zaleski, Stephane Kremer
Summary: The purpose of this study was to compare the costs and organizational benefits of diagnostic workup without and with MRI dedicated to the ED. The results showed that using MRI in the ED for diagnostic purposes can reduce clinical decision time and total costs, making it a relevant approach.
EUROPEAN RADIOLOGY
(2022)
Meeting Abstract
Respiratory System
Nicolas Migueres, Olivier Vandenplas, Hille Suojalehto, Jolanta Walusiak-Skorupa, Xavier Munoz, Joaquin Sastre, Rolf Merget, Gianna Moscato, Santiago Quirce, Nicolas Meyer, Julien Godet, Frederic De Blay
EUROPEAN RESPIRATORY JOURNAL
(2021)
Article
Pharmacology & Pharmacy
T. Fabacher, M. Schaeffer, N. Tuzin, F. Severac, Francois Lefebvre, M. Mielcarek, E-A Sauleau, N. Meyer, J. Godet
ANNALES PHARMACEUTIQUES FRANCAISES
(2020)
Review
Biophysics
Veronique Gasser, Morgane Malrieu, Anne Forster, Yves Mely, Isabelle J. Schalk, Julien Godet
QUARTERLY REVIEWS OF BIOPHYSICS
(2020)