Selzentry (maraviroc) / ViiV Healthcare - LARVOL DELTA

Discovery and exploration of disubstituted [1,2,5]oxadiazolo-[3,4-b]pyrazines as novel C-C chemokine receptor type 5 signaling inhibitors targeting the intracellular allosteric binding pocket. (PubMed, Eur J Med Chem) - "The therapeutic potential of C-C chemokine receptor type 5 inhibition has been demonstrated by antagonists targeting the extracellular domain, notably maraviroc, a Food and Drug Administration-approved Human Immunodeficiency Virus entry inhibitor...Molecular dynamics simulations and a competition assay with a Gαq11 mimetic were used to confirm the intracellular binding mode of these compounds. This novel class of C-C chemokine receptor type 5-selective intracellular antagonists offers a foundation for developing molecular tools and therapeutic agents, potentially overcoming the limitations of current extracellular C-C chemokine receptor type 5 antagonists."

Journal • Cardiovascular • Human Immunodeficiency Virus • Infectious Disease • Oncology

Male-Dominant Spinal Microglia Contribute to Neuropathic Pain by Producing CC-Chemokine Ligand 4 Following Peripheral Nerve Injury. (PubMed, Cells) - "Intrathecal administration of maraviroc, an inhibitor of the CCL4-CC-chemokine receptor 5 (CCR5) signaling pathway, after PSL, significantly suppressed mechanical allodynia only in male mice. Furthermore, intrathecal administration of CCL4 induced mechanical allodynia in both sexes, accompanied by increased expression of c-fos, a neuronal excitation marker, in the SDH. These findings highlight a sex-biased difference in the gene expression profile of spinal microglia following peripheral nerve injury, with elevated CCL4 expression in male mice potentially contributing to pain exacerbation."

Journal • Inflammation • Neuralgia • Pain • CCL4 • FOS

Traffic control: Mechanisms of ligand-specific internalization and intracellular distribution of CCR5. (PubMed, Mol Pharmacol) - "A CCR5 inhibitor Maraviroc has been approved for blocking HIV entry; however, inhibitors for the treatment of other diseases have had limited success, likely because of the complexity of CCR5 pharmacology and biology...It responds to different ligands with distinct signaling and trafficking behaviors; notably, some ligands induce retention of the receptor inside the cell. This study reveals the cellular basis for receptor sequestration that can be exploited as a therapeutic strategy for inhibiting CCR5 function."

Journal • Human Immunodeficiency Virus • Infectious Disease • Oncology

Preclinical systematic review of CCR5 antagonists as cerebroprotective and stroke recovery enhancing agents. (PubMed, Elife) - "CCR5 antagonists demonstrate promise; however, rigorously designed preclinical studies that better align with STAIR/SRRR recommendations and downstream clinical trials are warranted. Prospective Register of Systematic Reviews (PROSPERO CRD42023393438)."

Journal • Preclinical • Review • Cardiovascular

ALKBH5 Regulates Macrophage Senescence and Accelerates Atherosclerosis by Promoting CCL5 m6A Modification. (PubMed, Arterioscler Thromb Vasc Biol) - "The ALKBH5 inhibitor IOX1 and the CCR5 antagonist maraviroc were identified as potential clinical interventions for inhibiting senescent foamy macrophage formation and atherosclerosis progression. Myeloid ALKBH5 deletion attenuates atherosclerosis progression by suppressing the formation of senescent foamy macrophages and the recruitment of CD8+IFNγ+ T cells. These findings identify ALKBH5, CCL5, and CCR5 as novel therapeutic targets for atherosclerosis."

Journal • Atherosclerosis • Cardiovascular • ALKBH5 • APOE • CD68 • CD8 • IFNG • LYZ

Oligodendroglial precursor cells modulate immune response and early demyelination in a murine model of multiple sclerosis. (PubMed, Sci Transl Med) - "Antagonizing chemokine receptor 5 (CCR5) using a European Medicines Agency-approved drug, maraviroc, reduced immune cell infiltration, alleviated demyelination, and attenuated EAE progression. We found an OPC-orchestrated immune cellular network that instigates early demyelination, provides insight into MS pathophysiology, and suggests avenues for early interventions."

Journal • Preclinical • CNS Disorders • Immunology • Multiple Sclerosis • Solid Tumor • CD4 • ITGAM • OLIG2 • PDGFRA • WIF1

Impact of Antiretroviral Therapy (ART) Intensification on HIV-1 Virologic Markers (ACTG 5324) (CROI 2025) - "Background The A5324 trial investigated intensification with dolutegravir (DTG) +/- maraviroc (MVC) on neuropsychological performance (NP) in persons with HIV (PWH) and neurocognitive impairment (NCI) on suppressive ART. One limitation of this finding is that the DTG+MVC arm exhibited a lower percentage of CA-2LTR detectable at baseline, despite randomization (Figure). The reduction of CA-2LTR detection with DTG+MVC may indicate suppression of residual replication, but other mechanisms are possible like altered migration of CA-2LTR-postive CD4+ T cells."

Alzheimer's Disease • Cognitive Disorders • Human Immunodeficiency Virus • Infectious Disease • CD4

MARAVIROC: This Study is Assessing the Safety and Efficacy of Immune Inhibition as a Treatment to Prevent Primary Graft Dysfunction (clinicaltrials.gov) - P2 | N=120 | Not yet recruiting | Sponsor: University of California, San Francisco

New P2 trial • Acute Lung Injury • Respiratory Diseases • Transplantation

Maraviroc enhances Bortezomib sensitivity in multiple myeloma by inhibiting M2 macrophage polarization via PI3K/AKT/RhoA signaling pathway in macrophages. (PubMed, Cell Div) - "MVC reduced macrophage polarization and enhanced Bortezomib sensitivity in MM cells."

Journal • Hematological Malignancies • Multiple Myeloma • Oncology • CCL3 • CCR5 • RHOA

Investigating drug-liposome interactions using liposomal electrokinetic chromatography. (PubMed, Anal Bioanal Chem) - "Canagliflozin, which initially showed no electrophoretic mobility, migrated toward the anode in the presence of negatively charged liposomes. Mobility of positively charged substances, ambroxol and maraviroc, was suppressed by the interactions with liposomes...However, the effects were complex due to changes in API ionization and liposome surface charge, complicating the distinction between pH effects and liposome presence on API behavior. Our findings emphasize the significance of liposome composition, temperature, and pH in studying the interactions of liposomes with drugs, which is crucial for optimizing liposome-based drug delivery systems."

Journal

Repurposing lapatinib as a triple antagonist of chemokine receptors 3, 4, and 5. (PubMed, Mol Pharmacol) - "Although only the CCR5 antagonist maraviroc is US Food and Drug Administration-approved (for HIV), we curated data on CCR3, CCR4, and CCR5 antagonists from ChEMBL to develop and validate machine learning models. Using these models, we identified lapatinib as a potent inhibitor of CCR3, CCR4, and CCR5. Our study illustrates the potential of machine learning in identifying molecules for repurposing as antagonists for G protein-coupled receptors, including CCR3, CCR4, and CCR5, which have various therapeutic applications."

Journal • Age-related Macular Degeneration • Alzheimer's Disease • Asthma • Cardiovascular • CNS Disorders • Human Immunodeficiency Virus • Immunology • Infectious Disease • Macular Degeneration • Oncology • Ophthalmology • Pulmonary Disease • Respiratory Diseases • Retinal Disorders • CCR4

Skeletal muscle stem cells modulate niche function in Duchenne muscular dystrophy mouse through YY1-CCL5 axis. (PubMed, Nat Commun) - "Maraviroc-mediated pharmacological blockade of the CCL5/CCR5 axis effectively mitigates muscle dystrophy and improves muscle performance. Lastly, we demonstrate YY1 represses Ccl5 transcription by binding to its enhancer thus facilitating promoter-enhancer looping. Altogether, our study demonstrates the critical role of MuSCs in actively shaping their niche and provides novel insight into the therapeutic intervention of muscle dystrophy."

Journal • Preclinical • Duchenne Muscular Dystrophy • Fibrosis • Genetic Disorders • Immunology • Inflammation • Muscular Dystrophy • TGFB1 • YY1

Predicted environmental concentration (PEC), environmental risk assessment (ERA) and prioritization of antiretroviral drugs (ARVs) in seawater from Guarujá (Brazilian coastal zone). (PubMed, Mar Environ Res) - "Regarding the results of the mixture of ARVs, the ERA showed a high acute and/or chronic risk for all five classes tested, i.e., (i) nucleoside/nucleotide reverse transcriptase inhibitors; ii) non-nucleoside reverse transcriptase inhibitors; iii) protease inhibitors; (iv) integrase strand transfer inhibitors; and (v) chemokine receptor antagonists. Ultimately, the final ranking of the OPBT approach was etravirine (the highest-priority ARV in seawater from Guarujá), followed by: nevirapine > efavirenz > ritonavir > lopinavir > maraviroc > atazanavir > darunavir > abacavir > dolutegravir > zidovudine > tenofovir > lamivudine."

Journal • Human Immunodeficiency Virus • Infectious Disease

CCL5 Induces a Sarcopenic-like Phenotype via the CCR5 Receptor. (PubMed, Antioxidants (Basel)) - "The participation of CCR5 was evaluated using the antagonist maraviroc (MVC)...When the CCR5 was antagonized, the effects produced by rCCL5 were prevented. In conclusion, we report for the first time that CCL5 is a novel myokine that exerts a sarcopenic-like effect through the CCR5 receptor."

Journal • Sarcopenia • Targeted Protein Degradation • CCL5

Maraviroc/cisplatin combination inhibits gastric cancer tumoroid growth and improves mice survival. (PubMed, Biol Res) - "This finding suggests that MVC/CDDP combination could be a potential complementary therapy for GC."

Journal • Preclinical • Gastric Cancer • Oncology • Solid Tumor

Sex Affects Cognitive Outcomes in HIV-1 Tat Transgenic Mice: Role of CCR5. (PubMed, ASN Neuro) - "Well-powered cohorts of male and female mice were placed on a diet containing doxycycline to induce Tat expression for 8-wks...Deficits in the males were fully reversed by the CCR5 antagonist, maraviroc (MVC)...Based on earlier work, we hypothesized that MVC might increase brain-derived neurotrophic factor (BDNF), which is essential in maintaining synaptodendritic function. MVC did increase the mBDNF to proBDNF ratio in males, perhaps contributing to improved cognition."

Journal • Preclinical • CNS Disorders • Cognitive Disorders • Developmental Disorders • Human Immunodeficiency Virus • Infectious Disease • BDNF • CD4

Antiviral Clinical Trial for Long Covid-19 (clinicaltrials.gov) - P2 | N=90 | Recruiting | Sponsor: Icahn School of Medicine at Mount Sinai | Not yet recruiting ➔ Recruiting

Enrollment open • Human Immunodeficiency Virus • Infectious Disease • Novel Coronavirus Disease

Elucidating the molecular mechanisms of CCR5-containing extracellular vesicles in vitro and in a rat model of experimental Rheumatoid arthritis. (PubMed, Int Immunopharmacol) - "In conclusion, this study provides valuable insights into one of the molecular mechanisms underlying RA pathogenesis, emphasizing the importance of EVsRASF and CCR5 in mediating synovial inflammation and joint destruction. The results underscore the potential of CCR5 as a therapeutic target, opening avenues for the development of targeted interventions in RA treatment with synovial fibroblast derived EVs serving as a convenient, stabilizing vehicle for delivering Maraviroc into the RA affected joint tissues."

Journal • Preclinical • Immunology • Inflammation • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

Treatments for Long COVID autonomic dysfunction: a scoping review. (PubMed, Clin Auton Res) - "Existing studies on the treatment of Long COVID autonomic dysfunction are often small and uncontrolled, making it unclear whether the observed pre-post changes were due solely to the administered treatments. Guidelines display some overlap, and we identified no direct contradictions. Unpublished/ongoing studies may shed light on this critical area of patient management."

Journal • Review • Fatigue • Gastrointestinal Disorder • Novel Coronavirus Disease

Investigating the combination of Temsavir and entry inhibitors on HIV replication: Synergistic and antagonistic effects observed against various R5-tropic envelopes. (PubMed, Virology) - "Here, we investigated the effects of combining Temsavir with other HIV entry inhibitors, including CD4 mimetic BNM-III-170, T20 or enfuvirtide, Ibalizumab, and Maraviroc. These results are promising for the potential of co-administrating antiretrovirals for HIV treatment and highlights the importance of developing advanced antiviral strategies. On the other hand, the variable responses against different R5-tropic envelopes underscore the complexity of designing universally effective combination antiviral therapies."

Journal • Human Immunodeficiency Virus • Infectious Disease • CD4

The CCL5/CCR5/SHP2 axis sustains Stat1 phosphorylation and activates NF-κB signaling promoting M1 macrophage polarization and exacerbating chronic prostatic inflammation. (PubMed, Cell Commun Signal) - "These findings establish the CCL5/CCR5 axis as a critical driver of persistant prostatic inflammation and present it as a potential therapeutic target for CP."

Journal • Immunology • Inflammation • CCR5

Treatment Cost of Heavily Treatment-Experienced Adult Patients With Multi-Drug Resistant HIV-1 Infection in Brazil (ISPOR-EU 2024) - " The total cost of a patient is BRL 100,528, 77% of which is related to ART regimens, with maraviroc and enfuvirtide representing the costly treatments and being included in 19% and 10% of optimized background therapy (OBT) regimens, respectively. Patients with lower CD4+ cell counts require a higher level of healthcare resources with the potential to overload the system with higher costs for treatment and disease control. New technologies aimed at controlling the progression of HIV-1 and CD4+ cell counts can contribute to better quality of life and reduced healthcare resource utilization by the Sistema Único de Saúde (SUS)."

Clinical • Treatment costs • Human Immunodeficiency Virus • Infectious Disease • CD4

Safety and efficacy of doravirine plus tenofovir alafenamide/emtricitabine/bictegravir (TAF/FTC/BIC) in heavily pre‐treated patients (HIV-Glasgow 2024) - "Prior ARV was INSTI based in 12 cases (52%), PI based in one (4%), and both INSTI and PI in 10 (43%), with additional maraviroc in three cases (13%)...Among the four subjects with persistent low-grade viraemia, two changed to long-acting cabotegravir/rilpivirine with virological success, and two maintained the combination with last available HIV RNA of 1.82 and 1.90 logs, respectively. The use of DOR plus TAF/FTC/BIC in heavily pre-treated patients was safe—no withdrawals due to toxicity—and led to undetectable HIV RNA in 76% of patients with prior viral failure."

Clinical • Human Immunodeficiency Virus • Infectious Disease • CD4

Rhodium-Catalyzed Asymmetric Reductive Hydroformylation of α-Substituted Enamides. (PubMed, J Am Chem Soc) - "DFT calculations and experimental data have revealed the importance of hydrogen bonding between the N-H group in the structure of TFPNH-BIBOP and the enamide carbonyl group in promoting both high enantioselectivity and reactivity. This method has enabled the concise synthesis of several chiral pharmaceutical intermediates including a single-step synthesis of the key chiral intermediate of maraviroc."

Journal

Risk of viral failure after simplification therapy without using integrase inhibitors compared with maintenance of triple antiretroviral therapy: A systematic review and meta-analysis. (PubMed, Braz J Infect Dis) - "Simplification therapy with boosted PI plus lamivudine or non-nucleoside transcriptase reverse inhibitors was a safe strategy and not associated with a higher risk of virological failure. This approach might be an alternative to dolutegravir-based simplification regimens if needed."

Journal • Retrospective data • Review • Human Immunodeficiency Virus • Infectious Disease