Results 31 to 40 of about 6,218 (156)

Plasmepsins as Antimalarial Drug Targets—Then, Now, and the Future

Medicinal Research Reviews, EarlyView.
ABSTRACT Malaria is a devastating disease caused by Plasmodium parasites. Plasmodium parasites express ten cathepsin D‐like aspartyl proteases, called plasmepsins (PMs). These PMs have diverse roles fulfill diverse functions throughout the parasite's lifecycle, though several exhibit functional redundancies. Among them, PMV, PMIV, and PMX are essential
Brad E. Sleebs
wiley   +1 more source

Development of a physiologically‐based pharmacokinetic model for Ritonavir characterizing exposure and drug interaction potential at both acute and steady‐state conditions

CPT: Pharmacometrics &Systems Pharmacology, Volume 14, Issue 3, Page 523-539, March 2025.
Abstract Ritonavir (RTV) is a potent CYP3A inhibitor that is widely used as a pharmacokinetic (PK) enhancer to increase exposure to select protease inhibitors. However, as a strong and complex perpetrator of CYP3A interactions, RTV can also enhance the exposure of other co‐administered CYP3A substrates, potentially causing toxicity.
Lien Thi Ngo, Woojin Jung, Tham Thi Bui, Hwi‐yeol Yun, Jung‐woo Chae, Jeremiah D. Momper   +5 more
wiley   +1 more source

Substitutions in SARS-CoV-2 Mpro Selected by Protease Inhibitor Boceprevir Confer Resistance to Nirmatrelvir

Viruses, 2023
Nirmatrelvir, which targets the SARS-CoV-2 main protease (Mpro), is the first-in-line drug for prevention and treatment of severe COVID-19, and additional Mpro inhibitors are in development.
Karen Anbro Gammeltoft, Yuyong Zhou, Line Abildgaard Ryberg, Long V. Pham, Alekxander Binderup, Carlos Rene Duarte Hernandez, Anna Offersgaard, Ulrik Fahnøe, Günther Herbert Johannes Peters, Santseharay Ramirez, Jens Bukh, Judith Margarete Gottwein   +11 more
doaj   +1 more source

Covalent drug discovery: Progress against key targets, emerging strategies and lessons learnt

British Journal of Pharmacology, EarlyView.
Abstract Covalent drug discovery is currently experiencing a boom in industrial and academic interest. To date, at least 75 covalent drugs have received regulatory approval, targeting both traditional target classes and more challenging proteins for which other approaches failed. In many cases, unique aspects of covalent targeting are essential for the
Charles P. Brown, Alan Armstrong, David J. Mann   +2 more
wiley   +1 more source

Impact of extended-course oral nirmatrelvir/ritonavir in established Long COVID: a case series

Communications Medicine
Background Prior case series suggest that a 5-day course of oral Paxlovid (nirmatrelvir/ritonavir) benefits some people with Long COVID, within and/or outside of the context of an acute reinfection.
Alison K. Cohen, Toni Wall Jaudon, Eric M. Schurman, Lisa Kava, Julia Moore Vogel, Julia Haas-Godsil, Daniel Lewis, Samantha Crausman, Kate Leslie, Siobhan Christine Bligh, Gillian Lizars, JD Davids, Saniya Sran, Michael Peluso, Lisa McCorkell   +14 more
doaj   +1 more source

Targeting protein–protein interactions with reversible covalent modalities: Non‐cysteine chemistries

British Journal of Pharmacology, EarlyView.
Abstract Protein–protein interactions (PPIs) are central to diverse cellular functions, and represent a rapidly expanding class of therapeutic targets. Advancements in covalent drug design have enabled small‐molecule drugs to overcome challenges associated with engaging these targets, such as limited durations of action and difficult‐to‐drug (expansive,
Ruchira Basu, Steven Fletcher
wiley   +1 more source

Thermodynamic characterisation of covalent ligand binding

British Journal of Pharmacology, EarlyView.
Background and Purpose Differential scanning fluorimetry (DSF) is a common and straightforward method to evaluate the thermal stability of proteins and has been heavily used for ligand binding characterisation as well as for screening. One class of compounds that is less typically evaluated by DSF are covalent binders.
Rebecca Hertzman, Maayan Lavie, Almog Nadir, Ronen Gabizon, Nir London   +4 more
wiley   +1 more source

Exploration of Nirmatrelvir Derivatives as Optimized SARS‐CoV‐2 Antivirals

ChemMedChem, Volume 21, Issue 15, 14 August 2026.
Structure‐guided optimization of nirmatrelvir identifies aldehyde and dichloroacetamide warheads and a potency‐enhancing S4 thioamide. Crystal structures reveal an S2 rearrangement extending toward Cys44, suggesting a new covalent‐design opportunity.
Yugendar R. Alugubelli, Veerabhadra R. Vulupala, Kai S. Yang, Kaustav Khatua, Lauren R. Blankenship, Sathish Kumar, Demonta Coleman, Xuejiao Guo, Zhi Zachery Geng, Chia‐Chuan D. Cho, Banumathi Sankaran, Benjamin W. Neuman, Shiqing Xu, Wenshe Ray Liu   +13 more
wiley   +1 more source

B‐Cell Depletion Relative to Tumor Necrosis Factor Inhibition Extends the Duration of Viral Shedding in COVID‐19 Among Autoimmune Disease Patients: A Matched Prospective Cohort Study

ACR Open Rheumatology, Volume 8, Issue 8, August 2026.
Objective To investigate SARS‐CoV‐2 viral shedding duration in autoimmune patients using B cell depleting (BCD) therapy or tumor necrosis factor inhibitors (TNFi) and immunocompetent comparators. Methods We conducted a matched cohort analysis among participants in POSITIVES, a prospective study enrolling outpatients with acute COVID‐19 within five days
Liya Sisay Getachew, Xiaosong Wang, Naomi J. Patel, Zachary S. Wallace, Lauren A. O'Keeffe, Madison Negron, Jiaqi Wang, Grace Qian, Alene A. Saavedra, Kevin T. Mueller, Natalie Davis, Yijia Li, Brooke M. Leeman, Manish C. Choudhary, Sebastien Haneuse, Luke Benz, Julie Boucau, Gregory E. Edelstein, Owen T. Glover, Yumeko Kawano, Rinki Deo, Zahra Reynolds, Karry Su, Chase B. Mandell, Zoie Smith‐Sparks, Eliza Passell, Mamadou Oury Barry, Dessie Tien, Sarah P. Hammond, Gaurav D. Gaiha, Jacob E. Lemieux, Amy K. Barczak, Jonathan Z. Li, Mark J. Siedner, Jeffrey A. Sparks   +34 more
wiley   +1 more source

Emerging small-molecule antiviral agents in long COVID prevention

Frontiers in Pharmacology
Long COVID, or Post-Acute Sequelae of COVID-19 (PASC), was characterized by persistent symptoms such as fatigue, shortness of breath, and cognitive impairments.
Xiaomeng He, Xiang Zhang, Wu Zhong
doaj   +1 more source