Article
Medicine, General & Internal
Bruce K. Patterson, Ram Yogendra, Jose Guevara-Coto, Rodrigo A. Mora-Rodriguez, Eric Osgood, John Bream, Purvi Parikh, Mark Kreimer, Devon Jeffers, Cedric Rutland, Gary Kaplan, Michael Zgoda
Summary: Post-acute sequelae of COVID (PASC), also known as long COVID, is a debilitating complication of SARS-CoV-2 infection. Recent research suggests that targeting certain receptors using drugs like maraviroc and pravastatin may improve symptoms and restore immune dysregulation in PASC. A pilot study with 18 participants showed significant clinical improvement in neurological, autonomic, respiratory, cardiac, and fatigue symptoms after 6 to 12 weeks of treatment with maraviroc and pravastatin.
FRONTIERS IN MEDICINE
(2023)
Review
Medicine, Research & Experimental
Omozojie P. Aigbogun, Christopher P. Phenix, Ed S. Krol, Eric W. Price
Summary: Small-molecule drugs have short in vivo half-lives, hindering their success as therapeutics. Chemically programmed antibodies (cPAbs) have been developed to address these limitations by augmenting small molecules with antibodies for effector functions and prolonged pharmacokinetic profiles. This review summarizes the different methods used to produce cPAbs and highlights their potential applications in antibody modification fields.
MOLECULAR PHARMACEUTICS
(2023)
Article
Microbiology
Xiao L. Chang, Jason S. Reed, Gabriela M. Webb, Helen L. Wu, Jimmy Le, Katherine B. Bateman, Justin M. Greene, Cleiton Pessoa, Courtney Waytashek, Whitney C. Weber, Joseph Hwang, Miranda Fischer, Cassandra Moats, Oriene Shiel, Rachele M. Bochart, Hugh Crank, Don Siess, Travis Giobbi, Jeffrey Torgerson, Rebecca Agnor, Lina Gao, Kush Dhody, Jacob P. Lalezari, Ivo Sah Bandar, Alnor M. Carnate, Alina S. Pang, Michael J. Corley, Scott Kelly, Nader Pourhassan, Jeremy Smedley, Benjamin N. Bimber, Scott G. Hansen, Lishomwa C. Ndhlovu, Jonah B. Sacha
Summary: The CCR5-specific antibody Leronlimab has shown to be a safe and effective immunotherapy for suppressing HIV replication without significant side effects. It can fully occupy CCR5 receptors on CD4+ T cells and monocytes, leading to long-term virologic suppression in both humans and macaques.
Article
Oncology
Yuan Zhuang, Xiaomei Zhao, Baoying Yuan, Zhaochong Zeng, Yixing Chen
Summary: The study showed that the CCR5 antagonist MVC can induce macrophage polarization towards the M1 phenotype by blocking the CCL5-CCR5 signaling pathway, thereby enhancing the sensitivity and apoptosis of human hepatoma cells to radiation.
JOURNAL OF HEPATOCELLULAR CARCINOMA
(2021)
Article
Immunology
Yerkezhan Amerzhanova, Luca Vangelista
Summary: This perspective provides an overview of CCR5 as a central molecular determinant and its potential therapeutic applications. The study focuses on CCR5 antagonism and its impact on receptor-ligand interactions. The analysis of CCL5 mutants reveals the potential for enhanced anti-HIV-1 activity. Furthermore, the exploration of strategies such as improving CCR5 interaction in regions distal to the chemokine N-terminus and developing allosteric antagonists opens up new possibilities for CCR5 blockade.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Allergy
Marc Gauthier, Sagar Laxman Kale, Timothy B. Oriss, Kathryn Scholl, Sudipta Das, Huijuan Yuan, Sanmei Hu, Jie Chen, Matthew Camiolo, Prabir Ray, Sally Wenzel, Anuradha Ray
Summary: This study investigated the role of chemotactic receptors CXCR3 and CCR5 in establishing type 1 inflammation in severe asthma. The results showed a strong correlation between CXCR3, CCR5, and IFN-γ expression. Inhibiting the CCR5 pathway with maraviroc reduced airway hyperreactivity. Targeting this pathway may be a novel approach for improving lung function in individuals with type 1-high asthma.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Article
Immunology
Stephanie M. Matt, Emily A. Nickoloff-Bybel, Yi Rong, Kaitlyn Runner, Hannah Johnson, Margaret H. O'Connor, Elias K. Haddad, Peter J. Gaskill
Summary: The study suggests that drug-induced increases in central nervous system dopamine levels may be a common mechanism by which distinct addictive substances alter neuroHIV. Dopamine can affect HIV replication and alter the conformation of immune cells, highlighting the importance of dopamine in the development of neuroHIV.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Medicine, Research & Experimental
Michael R. Ruff, Saadet Inan, Xiang Qun Shi, Joseph J. Meissler, Martin W. Adler, Toby K. Eisenstein, Ji Zhang
Summary: RAP-103, when co-administered with morphine, reduces the dose of morphine required for pain relief and the associated side effects. It also shows effectiveness as a non-opioid treatment for diabetic neuropathic pain.
Article
Chemistry, Medicinal
Robert J. Cherney, Prakash Anjanappa, Kumaravel Selvakumar, Douglas G. Batt, Gregory D. Brown, Anne Rose, Ragini Vuppugalla, Jing Chen, Jian Pang, Songmei Xu, Melissa Yarde, Andrew J. Tebben, Venkatram Reddy Paidi, Mary Ellen Cvijic, Arvind Mathur, Joel C. Barrish, Sandhya Mandlekar, Qihong Zhao, Percy H. Carter
Summary: Compound 3, identified as a potent and selective CCR2/5 dual antagonist, demonstrated excellent permeability and stability in vitro, as well as promising pharmacokinetic properties in animal studies, ultimately leading to its selection as a clinical candidate.
ACS MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Chemistry, Multidisciplinary
Samilla B. Rezende, Karen G. N. Oshiro, Nelson G. O. Junior, Octavio L. Franco, Marlon H. Cardoso
Summary: Antimicrobial peptides (AMPs) are seen as promising molecules against antibiotic-resistant bacterial infections, but face limitations such as enzymatic degradation, chemical/physical instability, and toxicity towards healthy human cells in clinical trials. To improve their therapeutic potential, chemical modifications like peptidomimetic approaches are promising strategies to fine-tune AMPs.
CHEMICAL COMMUNICATIONS
(2021)
Article
Chemistry, Medicinal
Takaki Nakajima, Kazuya Nagano, Yuka Fukuda, Yu Ishima, Hiroko Shibata, Ryo Isaka, Tian-qi Zhang, Yuya Haga, Kazuma Higashisaka, Hirofumi Tsujino, Tatsuhiro Ishida, Akiko Ishii-Watabe, Yasuo Tsutsumi
Summary: Bioconjugation with polyethylene glycol (PEG) is important for protein drug development, but proteins including PEGylated ones are prone to aggregation or subvisible particle formation under dropping stress. In this study, different lengths and numbers of PEG-OVA molecules were prepared and analyzed under dropping stress, revealing that 20 kDa PEG-OVA formed approximately three times the aggregated particle concentration compared to regular OVA solution, leading to the production of anti-PEG antibodies and clearance of PEG-OVA.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Immunology
Xiao L. Chang, Helen L. Wu, Gabriela M. Webb, Meenakshi Tiwary, Colette Hughes, Jason S. Reed, Joseph Hwang, Courtney Waytashek, Carla Boyle, Cleiton Pessoa, Andrew W. Sylwester, David Morrow, Karina Belica, Miranda Fischer, Scott Kelly, Nader Pourhassan, Rachele M. Bochart, Jeremy Smedley, Christopher P. Recknor, Scott G. Hansen, Jonah B. Sacha
Summary: CCR5 plays a central role in infectious diseases, host defense, and cancer progression, making it an ideal target for therapeutic development. The study introduces two flow cytometric methods for calculating CCR5 RO, showing sensitivity and correlation in macaques treated with Leronlimab.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Mushtaq A. Ansari, Ahmed Nadeem, Saleh A. Bakheet, Sabry M. Attia, Mudassar Shahid, Faris S. Alyousef, Mohammed A. Alswailem, Mohammed Alqinyah, Sheikh F. Ahmad
Summary: This study demonstrates that MVC has therapeutic potential in attenuating the severity of inflammatory arthritis in CIA mice by reducing pro-inflammatory responses and increasing anti-inflammatory responses.
Article
Immunology
Sihui Zhu, Lijuan Bian, Jia Lv, Baorui Liu, Jie Shen
Summary: This case report describes a male patient who developed non-bacterial cystitis after receiving immunotherapy, with recurrent urinary tract discomfort leading to surgery. Multiple urine cultures and cystoscopy biopsy confirmed the diagnosis of non-bacterial bladder inflammation.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Chemistry, Multidisciplinary
T. Tedeschini, B. Campara, A. Grigoletto, M. Bellini, M. Salvalaio, Y. Matsuno, A. Suzuki, H. Yoshioka, G. Pasut
Summary: ADCs are a promising therapeutic entity, with research focusing on exploring novel linker-drug architectures to improve their efficacy and stability. Studies have shown that using linkers containing monodisperse poly(ethylene glycol) moieties can enhance the stability and in vivo performance of ADCs.
JOURNAL OF CONTROLLED RELEASE
(2021)