Crixivan (indinavir sulfate) / Merck (MSD) - LARVOL DELTA

Structure-Based drug repurposing and experimental validation of inhibitors targeting LigaseD from Mycobacterium tuberculosis. (PubMed, Arch Biochem Biophys) - "Functional microbiological assays confirmed that under oxidative stress, when NHEJ is critical, indinavir-treated cells displayed reduced survival, consistent with impaired DNA repair. These findings indicate that L-756423/ Indinavir may hold therapeutic potential against latent tuberculosis and provide a rationale for further experimental investigation."

Journal • Human Immunodeficiency Virus • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Metabolic reprogramming of hippocampal endothelial cells contributes to blood-brain barrier dysfunction in perioperative neurocognitive disorder. (PubMed, Biochem Biophys Res Commun) - "Anesthesia and surgery induce metabolic reprogramming in hippocampal endothelial cells, alterations pathways central to amino acid, lipid, nucleotide, and carbohydrate metabolism. These endothelial metabolic alterations may underlie BBB dysfunction and contribute to the pathogenesis of PND."

Journal • Anesthesia • CNS Disorders • Cognitive Disorders • Developmental Disorders

Insights into Antiviral Candidates against Oropouche Virus: A Molecular Dynamics Study. (PubMed, ACS Phys Chem Au) - "While docking initially ranked Saquinavir as the top binder, subsequent MD simulations revealed that nelfinavir and indinavir exhibited superior performance across multiple criteria, including binding energy, structural stability, center-of-mass distance maintenance, and consistent hydrogen bonding. These findings emphasize the limitations of docking-only approaches and highlight the importance of dynamic and energetic analyses for accurate inhibitor selection. The proposed computational pipeline demonstrates its value in identifying stable, high-affinity ligands and offers a promising route for accelerating drug discovery against neglected viral diseases such as OROV."

Journal • Human Immunodeficiency Virus • Infectious Disease

The cleavage of indinavir sulfate: synthesis and characterization of a cis-1-amino-2-indanol salt. (PubMed, Acta Crystallogr C Struct Chem) - "The van der Waals surface area (687.30 Å2) accounts for 71.43% of the unit cell. These results provide structural and thermal evidence for the transformation of indinavir sulfate under alcoholytic conditions, highlighting the formation and stabilization of the resulting salt."

Journal • Addiction (Opioid and Alcohol) • Human Immunodeficiency Virus • Infectious Disease • CDKN1A

Screening for Potential Compounds Using Drug-Repurposing of N-Methyl-D-Aspartate (NMDA) Receptor for Autism Spectrum Disorder (ASD). (PubMed, Trop Life Sci Res) - "The drugs were alitretinoin, salicylic acid and indinavir, respectively. Finally, ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) predictions identify 4-androstenedione, tryptophan, carbocisteine and vitamin A as having minimal toxic effects. This study showed that alitretinoin, which was known to treat skin lesions from Kaposi's sarcoma, might have the ability to reverse the effect in ASD, particularly in NMDA receptors, potentially making a significant impact on the field of neurology and psychiatry."

Journal • Autism Spectrum Disorder • Genetic Disorders • Kaposi Sarcoma • Oncology • Psychiatry • Sarcoma • Solid Tumor • NRXN1

Nail the diagnosis: Lamivudine-induced periungual pyogenic granulomas in PLHIV. (PubMed, IDCases) - "A 30-year-old male living with HIV presented with painful, progressively enlarging ulcero-proliferative lesions on the fingertips and toes, occurring 12 months after initiating highly active antiretroviral therapy (HAART) comprising Tenofovir disoproxil (300 mg), Lamivudine (300 mg), and Dolutegravir (50 mg)...Among ART agents, lamivudine and indinavir have been most frequently associated with periungual PGs...Periungual pyogenic granulomas can lead to significant discomfort and functional impairment. This case highlights the potential role of lamivudine as a causative agent and underscores the importance of ART modification in the effective management of drug-induced PG."

Journal • Angiosarcoma • Human Immunodeficiency Virus • Infectious Disease • Kaposi Sarcoma • Non-melanoma Skin Cancer • Oncology • Pain • Sarcoma • Solid Tumor

Drugs repurposed against morphine and heroin dependence: molecular docking, DFT, MM-GBSA-based MD simulation studies. (PubMed, In Silico Pharmacol) - "We found vilazodone, indinavir, and lorazepam as potential drugs based on their affinity and mechanism of action. We propose that these three drugs have huge potential to reverse the morphine and heroin dependence in diseased subjects near future. The online version contains supplementary material available at 10.1007/s40203-025-00347-z."

Journal • Addiction (Opioid and Alcohol) • Pain • TLR4

Designing new pharmaceutical derivatives for potential inhibition of human immunodeficiency virus protease enzyme inhibition; a comprehensive in silico study. (PubMed, J Biomol Struct Dyn) - "This study conducts a comprehensive examination of the interaction between Indinavir and HIV protease, evaluating the functional efficacy of designed analogs based on Indinavir using docking tools...This study emphasizes the importance of innovative drug design approaches in addressing the evolving challenges posed by viral infections. However, it is imperative to acknowledge the necessity for further experimental validations to verify the current findings and ensure their relevance."

Journal • Human Immunodeficiency Virus • Infectious Disease

Insights into the interaction mechanism of first-generation HIV-1 protease inhibitors with wild-type and mutant (D30N and L76V) enzymes through in-silico based approach. (PubMed, J Biomol Struct Dyn) - "The present study focuses on to understand the alterations in wild-type and mutants (D30N and L76V) PR structure by interaction of first-generation PR inhibitors amprenavir, indinavir, nelfinavir, ritonavir and saquinavir. L76V mutant does not form any direct interaction with the first line drugs; hence the drugs forming strong interactions with the active site, flap domain and substrate binding region residues are quite enough to manage the resistance provided by L76V mutant. The results provided the insight into the drug-resistant or drug-susceptibility mechanism of L76V and D30N mutation against first-generation PR inhibitors."

Journal • Human Immunodeficiency Virus • Infectious Disease

Viremia Does Not Independently Predict Cardiovascular Disease in People With HIV: A RESPOND Cohort Study. (PubMed, Open Forum Infect Dis) - "We first analyzed the associations between 6 measures of viremia (time-updated, before antiretroviral therapy [ART], viremia category, and measures of cumulative viremia) and CVD after adjusting for the variables in the D:A:D CVD score (age, sex/gender, smoking, family history, diabetes, recent abacavir, CD4 count, blood pressure, cholesterol, high-density lipoprotein, cumulative use of stavudine, didanosine, indinavir, lopinavir, and darunavir). In this large international cohort, HIV viremia was not associated with CVD when adjusting for established risk factors. Our results did not show viremia to be predictive of CVD among people with HIV."

Journal • Cardiovascular • Diabetes • Human Immunodeficiency Virus • Infectious Disease • Metabolic Disorders • Myocardial Infarction • CD4

Interaction study between HIV protease inhibitors and alectinib in rats based on an ultra-performance liquid chromatography tandem mass spectrometry method. (PubMed, J Chromatogr B Analyt Technol Biomed Life Sci) - "Alectinib and lorlatinib (internal standard) were measured in MRM mode. The dosages should be adjusted when using atazanavir, darunavir, indinavir, and ritonavir with alectinib. Real-time monitoring should occur during treatment."

Journal • Preclinical • Human Immunodeficiency Virus • Infectious Disease

The role of weak interactions in evaluation of inhibitory potential of Indinavir as an HIV protease inhibitor and its comparison with innovative drug candidates. (PubMed, Comput Biol Med) - "Finally, molecular dynamics simulations were conducted to evaluate the inhibitory mechanism of the recommended inhibitor on the protease enzyme. The relevant analyses during the simulation period showed that the designed drug IND20 exhibited better performance in inhibiting the HIV-1 protease enzyme compared to Indinavir."

Journal • Human Immunodeficiency Virus • Infectious Disease

Drug-induced nephrolithiasis: a real-world pharmacovigilance study of the FDA adverse event reporting system. (PubMed, Expert Opin Drug Saf) - "The most frequently occurring drug was adalimumab, while the antiretroviral drug indinavir exhibited the strongest signal intensity. This comprehensive pharmacovigilance study has revealed many drugs potentially associated with an increased risk of nephrolithiasis. Notably, vigilant surveillance for nephrolithiasis risk while using these drugs is crucial in clinical practice."

Adverse events • Journal • Real-world • Real-world evidence • Nephrology • Renal Calculi

Multi-modal transcriptomics: integrating machine learning and convolutional neural networks to identify immune biomarkers in atherosclerosis. (PubMed, Front Cardiovasc Med) - "Molecular docking analyses explored therapeutic potential for Estradiol, Zidovudine, Indinavir, and Dronabinol for clinical applications. This study introduces three signature genes for atherosclerosis, shaping a novel paradigm for investigating clinical immunological medications. It distinguishes the high biocidal C2 subtype from the inflammation-modulating C1 subtype, utilizing identified signature gene as crucial targets."

Biomarker • Journal • Machine learning • Atherosclerosis • Cardiovascular • Inflammation • CD36 • CSNK1A1 • S100A10 • SCARB1

Transcellular transport of 18F-deoxyglucose via facilitative glucose channels in experimental peritoneal dialysis. (PubMed, Perit Dial Int) - "The present results indicate that part of glucose is transported via the transcellular route across cells in the peritoneal membrane. Regardless of the channel(s) involved, inhibitors of facilitative GLUTs may be promising agents to improve UF efficacy in patients treated with PD."

Journal

Evaluation of inhibition effect and interaction mechanism of antiviral drugs on main protease of novel coronavirus: Molecular docking and molecular dynamics studies. (PubMed, J Mol Graph Model) - "The interaction mechanism between antiviral drugs and main protease was analyzed in detail by calculating the root mean square displacement (RMSD), root mean square fluctuation (RMSF) and interaction residues properties. The results showed that the six drugs with high flexibility (Remdesivir, Simnotrelvir, Sofosbuvir, Ledipasvir, Indinavir and Raltegravir) had strong binding strength with 3CLpro, and the last four antiviral drugs can be used as potential candidates for main protease inhibitors."

Journal • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

Detailed modelling of viremia exposure does not independently predict cardiovascular disease in people with HIV (AIDS 2024) - "We fitted Cox models including the variables in the D:A:D score (age, gender, smoking, family history, diabetes, current abacavir, CD4 count, blood pressure, cholesterol, high-density lipoprotein, stavudine, didanosine, indinavir, lopinavir, and darunavir; all time-updated). In this large cohort, HIV viremia was not associated with CVD after adjusting for established risk factors. Although we are unable to analyze the impact of viremia before HIV diagnosis, our results provide evidence against a role for viral load in predicting CVD among people with HIV."

Cardiovascular • Diabetes • Human Immunodeficiency Virus • Infectious Disease • Metabolic Disorders • Myocardial Infarction • CD4

Clinical efficacy of the HIV protease-inhibitor Indinavir alone or in combination with chemotherapy for the treatment of early and advanced classic Kaposi's sarcoma (AIDS 2024) - "Our results indicate that Indinavir is safe and effective in early CKS, it boosts and maintains the clinical activity of conventional chemotherapy in advanced disease, and it could be rapidly adopted for the clinical management of persons with KS or other tumors associated or not with HIV infection."

Clinical • Combination therapy • Metastases • Epstein-Barr Virus Infections • Human Immunodeficiency Virus • Infectious Disease • Kaposi Sarcoma • Oncology • Sarcoma • Solid Tumor

Genomic and computational-aided integrative drug repositioning strategy for EGFR and ROS1 mutated NSCLC. (PubMed, Int Immunopharmacol) - "Following, virtual screening and redocking analysis, Elbasvir, Ledipasvir, and Lomitapide drugs for EGFR mutants (>-10.8 kcal/mol) while Indinavir, Ledipasvir, Lomitapide, Monteleukast, and Isavuconazonium for ROS1 mutants (>-8.8 kcal/mol) were found as putative inhibitors. Furthermore, classical molecular dynamics simulation and endpoint binding energy calculation support the considerable stability of the selected docked complexes aided by substantial hydrogen bonding and hydrophobic interactions in comparison to the respective control complexes. Conclusively, the repositioned FDA-approved drugs might be beneficial alone or in synergy to overcome acquired resistance to EGFR and ROS1-positive lung cancers."

Journal • Tumor mutational burden • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • ROS1 • TMB

Clinical efficacy of the HIV protease-inhibitor Indinavir in combination with chemotherapy for advanced classic Kaposi's sarcoma treatment: a single-arm, phase II trial in the elderly. (PubMed, Cancer Res Commun) - "In advanced CKS a strategy combining Indinavir and chemotherapy is safe and associated with high and durable response rates, and it could be rapidly adopted for the clinical management of these patients."

Combination therapy • Journal • Metastases • P2 data • Epstein-Barr Virus Infections • Human Immunodeficiency Virus • Infectious Disease • Kaposi Sarcoma • Oncology • Sarcoma • Solid Tumor

Liver Steatosis is Prevalent in Lean People With HIV and Associated With Exposure to Antiretroviral Treatment-A Cross-sectional Study. (PubMed, Open Forum Infect Dis) - "Furthermore, in lean PLHIV, liver steatosis was associated with CD4 and CD8 counts at enrollment, dual therapy, and history of treatment with raltegravir (aOR: 3.6 [1.53-8.47], P = .003), stavudine (aOR: 3.73 [1.69-8.2], P = .001), and indinavir (aOR: 3.86 [1.59-9.37], P = .003). In addition, (prior) exposure to specific antiretroviral drugs was associated liver steatosis in lean, but not in overweight/obese PHIV. Implementing increased screening protocols could enhance the identification of steatotic liver disease in lean PHIV."

Journal • Observational data • Diabetes • Fibrosis • Hepatology • Human Immunodeficiency Virus • Immunology • Infectious Disease • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Type 2 Diabetes Mellitus • CD4 • CD8

Discovery and development of MK-7845 as an investigational treatment for COVID-19 (ACS-Sp 2024) - "This commitment has remained strong, as evidenced by the introduction of Crixivan™ for HIV, Zepatier™ for HCV, and Prevymis™ for CMV. Our company, like many others, initiated a multi-pronged approach to combat SARS-CoV-2; one major effort was focused on the discovery of an effective inhibitor of the viral 3-chymotrypsin-like protease (3CLPro). This presentation will focus on the invention and rapid development of MK-7845 as an oral protease inhibitor for the treatment of COVID-19."

Human Immunodeficiency Virus • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Identification and characterization of domain-specific inhibitors of DENV NS3 and NS5 proteins by in silico screening methods. (PubMed, J Biomol Struct Dyn) - "Our comprehensive analysis identified tolcapone, cefprozil, delavirdine and indinavir as potential inhibitors of NS5 MTase, NS5 RdRp, NS3 protease and NS3 helicase functions, respectively. These high-confidence candidate molecules will be useful for developing effective anti-DENV therapy to combat dengue infection.Communicated by Ramaswamy H. Sarma."

Journal • Dengue Fever • Infectious Disease

Conformational diversity and protein-protein interfaces in drug repurposing in Ras signaling pathway. (PubMed, Sci Rep) - "The results suggest that HIV protease inhibitors tipranavir, indinavir, and saquinavir may bind to EGFR and ERBB3/HER3 interface. Additionally, a drug used in Alzheimer's disease can bind to RAF1 and BRAF interface. Hence, we propose a methodology to find drugs to be potentially used for cancer using a dataset of structurally similar protein-protein interface clusters rather than pockets in a systematic way."

Journal • Alzheimer's Disease • CNS Disorders • Human Immunodeficiency Virus • Infectious Disease • Oncology • BRAF • EGFR • ERBB3 • HER-2

Predictions based on inflammatory cytokine profiling of Egyptian COVID-19 with 2 potential therapeutic effects of certain marine-derived compounds. (PubMed, Int Immunopharmacol) - "The investigated inflammatory biomarkers in Egyptian COVID-19 patients showed a strong correlation between IL6, TNF-α, NF-κB, CRB, DHL, and ferritin as COVID-19 biomarkers and determined the severity of the infection. Also, the oxidative /antioxidant showed good biomarkers for infection recovery and progression of the patients."

Journal • Cardiovascular • Critical care • Immunology • Infectious Disease • Inflammation • Metabolic Disorders • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases • CD8 • CXCL8 • IL6