Invirase (saquinavir) / Roche - LARVOL DELTA

Virtual screening of drugs against multiple targets of Alzheimer's disease. (PubMed, J Alzheimers Dis) - "BackgroundDrug repurposing offers a rapid, cost-effective approach for discovering therapies against multiple targets.ObjectiveHere, we screen virtual ligand libraries consisting of 3468 approved drugs against 11 protein targets associated with Alzheimer's disease (AD).MethodsWe employ blind molecular docking, and target amyloid-β (Aβ), microtubule-associated protein tau (MAPT), Apolipoprotein E4 (APOE4), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), amyloid-β protein precursor (AβPP), β-secretase (BACE1), brain-derived neurotrophic factor (BDNF), presenilin 1 (PSEN1) and 2 (PSEN2), and α-synuclein (SNCA) proteins using AutoDock Vina.ResultsNotably, multitarget binding recurs among the top-10 ligands with Ergotamine and Dihydroergotamine potentially binding 8; Dutasteride 7; Drospirenone and Nilotinib 6; Adapalene and Conivaptan 5; Bromocriptine 4; and Rolapitant, Irinotecan, Plerixafor, Saquinavir, and Telmisartan 3, out of 11 protein targets. Likewise,..."

Journal • Alzheimer's Disease • Cardiovascular • CNS Disorders • Hypertension • Inflammation • Pain • APOE • BDNF • MAPT • SNCA

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

Structure-based drug design; Computational strategies in drug discovery; Antihypertensive agents; Antiviral drugs; Molecular docking; QSAR; Pharmacological insights. (PubMed, Comput Biol Chem) - "This review meticulously examines the development, design, and pharmacological assessment of both well known antiviral and antihypertensive medications all time employing new chemical techniques and structure-based drug design to design and synthesize vital therapeutic entities such as aliskiren (renin inhibitor), captopril (a2-ACE-Inhibitor), dorzolamide (inhibitor of carbonic anhydrase) the review demonstrates initial steps regarding the significance of stereoselective synthesis, metal chelating pharmacophores, and rational molecular properties. More importantly, protease inhibitors (i.e., saquinavir, ritonavir, indinavir, amprenavir, etc.) and more contemporary agents (i.e., oseltamivir, nirmatrelvir/ritonavir (Paxlovid), etc.) were identified in the review and form a basis of advancement in antiviral therapy...In conclusion, this review highlights the transformative power of interdisciplinary approaches, including structure-based design, computational modeling, and..."

Journal • Review • Cardiovascular • Infectious Disease

Synthesis, Spectroscopic, Electronic and Molecular Docking Studies of Pyrazole Based Chalcones as Potential Anticancer Agents. (PubMed, J Fluoresc) - "Molecular docking against the 1B38 protease identified DF1 as the top binder (- 10.6 kcal/mol), outperforming the standard inhibitor Saquinavir (- 7.6 kcal/mol), via π-anion/cation interactions with Lys A:33 and Asp A:145, supported by ESP maps...Future work should prioritize in vitro validation and structural optimization to enhance selectivity and ADMET properties. This integrated approach highlights pyrazole-chalcones as promising anticancer scaffolds, with DF1 having superior binding and moderate toxicity warranting further development."

Journal • Oncology • CYP1A2

A computational effort to untangling anti-SARS-CoV-2 effects of oleanolic acid analogues. (PubMed, Pak J Pharm Sci) - "Through molecular docking and simulation studies, we found oleanolic acid (-12.6 Kcal/mol) and its two analogues (OA11; ligand I (-14.2 Kcal/mol)) and (OA31; ligand II (-14.0 Kcal/mol)) bound with Mpro (PDB: 6Y84) more reliable and trustful than saquinavir (-8.1 Kcal/mol) as a canonical drug. Salaspermic acid, (3b)-3-{[(2E)-3-phenylprop-2-enoyl]oxy}olean-12-en-28-oic acid, OA37 and OA40 interacted with catalytic dyad and major amino acid residues of active sites of Mpro and these toxic compounds should be considered in future anti-protease drug design. Overall, the current study seized the attention of experimentalists to the new set of anti-protease pentacyclic triterpenoids that should to be assayed against SARS-CoV-2 at in vitro or in clinical settings of COVID-19."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Computational design and evaluation of low-toxicity saquinavir analogues targeting the catalytic dyad and oxyanion-hole loop of SARS-CoV-2 Mpro: insights from ensemble docking, molecular dynamics, dynamic undocking, and ADMET analysis. (PubMed, Drug Chem Toxicol) - "Favorable ADMET profiles further support their potential as drug candidates with low mammalian toxicity. This study provides a strong foundation for experimental validation and the subsequent development of effective antiviral therapies against SARS-CoV-2."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Repurposing of approved drugs towards Nipah virus treatment: an in silico docking, molecular dynamics simulation and a MM/GBSA approach. (PubMed, In Silico Pharmacol) - "Binding affinities and 2D interaction profiles were analyzed, revealing five promising candidates: Saquinavir, Nelfinavir, Simeprevir, Paritaprevir, and Tipranavir. To evaluate their efficacy and contribute to the development of effective antiviral treatments against NiV, further in vivo testing in animal models and human trials is recommended. The online version contains supplementary material available at 10.1007/s40203-025-00371-z."

Journal • CNS Disorders • Infectious Disease

HIV protease inhibitors restore amphotericin B activity against Candida. (PubMed, PLoS One) - "In this study, we identified four HIV protease inhibitors (atazanavir, saquinavir, lopinavir and ritonavir) as strong potentiators of amphotericin B against C. auris. The in vivo treatment with HIV protease inhibitors combined with amphotericin B resulted in a significant reduction of C. auris colony-forming units (CFU) by 1.7-2.6 Log10 in the C. elegans model. These findings suggest that HIV protease inhibitors, in combination with amphotericin B, are promising candidates for the development of novel antifungal drugs to treat Candida infections."

Journal • Candidiasis • Human Immunodeficiency Virus • Infectious Disease

Host-Directed Therapies Based on Protease Inhibitors to Control Mycobacterium tuberculosis and HIV Coinfection. (PubMed, Microorganisms) - "In this review, we discuss the identification and development of new host-directed strategies based on protease inhibitors and their clinical relevance as adjunctive treatment. In the context of therapeutic agents with novel mechanisms, selective protease inhibitors, including saquinavir (SQV) and cystatins (CstC and CstF), are valuable targets that may provide effective therapeutic solutions for controlling Mtb and HIV coinfection."

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

Repurposing HIV protease inhibitors as senotherapeutic agents in cervical cancer: Dual targeting of CDK1/6-cell cycle arrest and p53/p21/p16 signaling axis. (PubMed, Biochem Biophys Res Commun) - "This study systematically investigates the antineoplastic potential of HIV protease inhibitors saquinavir (SQV) and tipranavir (TPV) through multimodal mechanistic validation...In vivo validation using xenograft models demonstrated comparable tumor growth inhibition to doxorubicin with preserved host viability and negligible systemic toxicity. Mechanistic integration revealed dual pathway modulation: G1-phase cell cycle arrest mediated through CDK1/6 suppression and coordinated activation of the p53/p21/p16 senescence signaling axis. These findings establish SQV and TPV as multi-targeted senotherapeutic agents, providing preclinical rationale for repurposing HIV antivirals as novel therapeutic strategy against cervical malignancies."

Journal • Cervical Cancer • Human Immunodeficiency Virus • Infectious Disease • Oncology • Solid Tumor • CDK1 • CDK6 • CDKN1A

Topical Saquinavir Prevents Anal Cancer Development Via PI3K Inhibition (ASCRS 2025) - "There was a trend, albeit not statically significant, in mice treated with SQV in the setting of DMBA exposure compared to DMBA alone. There was no statistically significant difference between groups with regards to pS6 quantification.Conclusion/ One mechanism through which topical SQV exerts its anal cancer preventative effects in vivo is via inhibition of PI3K, as noted by decreased pAKT expression.Figure 1: pKAT expression in mice treated with or without topical saquinavir and DMBA.pAKT expression was significantly decreased in mice treated with saquinavir alone compared with untreated control mice."

Anal Carcinoma • Oncology • Solid Tumor

Drug repositioning as a promising approach for the eradication of emerging and re-emerging viral agents. (PubMed, Mol Divers) - "Main repositioned drugs have included chloroquine, ivermectin, dexamethasone, Baricitinib, tocilizumab, Mab114 (Ebanga™), ZMapp (pharming), Artesunate, imiquimod, saquinavir, capmatinib, naldemedine, Trametinib, statins, celecoxib, naproxen, metformin, ruxolitinib, nitazoxanide, gemcitabine, Dorzolamide, Midodrine, Diltiazem, zinc acetate, suramin, 5-fluorouracil, quinine, minocycline, trifluoperazine, paracetamol, berbamine, Nifedipine, and chlorpromazine. This succinct review will delve into the topic of repositioned drugs that have been utilized to combat emerging and re-emerging viral pathogens."

Journal • Review • Chikungunya • Dengue Fever • Ebola Virus Disease • Hematological Disorders • Hepatology • Infectious Disease • Inflammation • Influenza • Novel Coronavirus Disease • Respiratory Diseases

A Prospective Cohort of Children With HIV Infection (clinicaltrials.gov) - P=N/A | N=500 | Completed | Sponsor: The HIV Netherlands Australia Thailand Research Collaboration | Trial completion date: Jun 2024 ➔ Sep 2024 | Trial primary completion date: Jun 2024 ➔ Sep 2024 | Active, not recruiting ➔ Completed

Trial completion • Trial completion date • Trial primary completion date • 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

Systematic Reevaluation of Repurposed Drugs Against the Main Protease of SARS-CoV-2 via Combined Experiments. (PubMed, J Med Virol) - "Our results from a set of in vitro assays revealed that boceprevir is a potential Mpro inhibitor, but other repurposed drugs, including atazanavir, dipyridamole, entrectinib, ethacridine, glecaprevir, hydroxychloroquine, ivermectin, meisoindigo, pelitinib, raloxifene, roxatidine acetate, saquinavir, teicoplanin, thonzonium bromide, and valacyclovir, are not. Our research highlights that the use of candidate Mpro inhibitors from primary screening warrants further comprehensive studies before the reporting of new findings."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

A genetically based computational drug repurposing framework for rapid identification of candidate compounds: application to COVID-19. (PubMed, medRxiv) - "Six (imiquimod, nelfinavir and saquinavir, everolimus, azathioprine, and retinol) had sufficient prescribing rates or feasibility for further testing. Crucially, our results highlight how a complementary evaluation-combining epidemiological data and in vitro assays-helps refine the most promising candidates for subsequent mechanistic studies and clinical trials. This integrated validation approach may prove vital for accelerating therapeutic development against current and future health challenges."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Repurposing raltegravir for reducing inflammation and treating cancer: a bioinformatics analysis. (PubMed, Sci Rep) - "Five FDA-approved drugs including Raltegravir, Conivaptan, Paclitaxel, Saquinavir, and Venetoclax with the ability to impede the activity of the ADAM17 metalloenzyme were identified. However, further in silico analysis has indicated that Raltegravir demonstrates a commendable interaction with the active site amino acids and exhibits the most favorable pharmacokinetic properties compared to others. Considering the results of bioinformatics tools, it can be concluded that Raltegravir as an antiviral drug could be repurposed to prevent severe inflammatory response and tumorigenesis resulting from ADAM17 malfunction."

Journal • Oncology • ADAM17

Magnetic nanoparticle-catalysed synthesis of quinoline derivatives: A green and sustainable method. (PubMed, Heliyon) - "Quinoline are considered a privileged structure among organic compounds and offer a promising avenue for identifying lead structures in the search of new synthetic molecules (Saquinavir, Imiquimod and Reabamipide) having potential medicinal values and other important prospects. So, it's always indeed to the organic and medicinal chemist to develop biologically active frameworks by the green synthesis. The current manuscript consolidates the existing research on properties of environment-friendly magnetic nanoparticles for generating an extended range of valuable quinoline derivatives."

Journal • Review

Epithelial mitochondrial fission-mediated PANoptosis is crucial for ulcerative colitis and its inhibition by saquinavir through Drp1. (PubMed, Pharmacol Res) - "Mechanistically, hyperactivated mitochondrial fission induced mitochondrial reactive oxygen species production leading to PANoptosis through ZBP1 sulfenylation at Cys327 independently of its Zα domain. Saquinavir, an FDA-approved drug identified through in-silico screening alongside in vivo and in vitro experiments, inhibits mitochondrial fission thereby enhancing therapeutic efficacy in mice with colitis."

Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis • IGF2BP1 • ZBP1

Early Intervention in IgA Nephropathy: An Update on a Potential Disease-Modifying Therapy (KIDNEY WEEK 2024) - "Avoid corticosteroid therapy, including TARPEYO, in patients with active or quiescent tuberculosis or hepatitis B infection; untreated fungal, bacterial, systemic viral, or parasitic infections; ocular herpes simplex; or Kaposi's sarcoma...Avoid use with potent CYP3A4 inhibitors, such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, erythromycin, and cyclosporine...Infants exposed to inutero corticosteroids, including budesonide, are at risk for hypoadrenalism. Please see Full Prescribing Information."

Acne Vulgaris • Cardiovascular • Cataract • Dermatitis • Dermatology • Dyspepsia • Gastroenterology • Glaucoma • Glomerulonephritis • Hepatitis B • Hepatology • Herpes Simplex • Hypertension • IgA Nephropathy • Immunology • Infectious Disease • Kaposi Sarcoma • Measles • Metabolic Disorders • Musculoskeletal Pain • Ocular Infections • Oncology • Ophthalmology • Osteoporosis • Pain • Peptic Ulcer • Renal Disease • Respiratory Diseases • Rheumatology • Sarcoma • Solid Tumor • Tuberculosis • Varicella Zoster

Topical Protease Inhibitor Increases Tumor-Free and Overall Survival in CD4-Depleted Mouse Model of Anal Cancer. (PubMed, Viruses) - "Transgenic K14E6/E7 mice with established high-grade anal dysplasia were treated topically at the anus with the protease inhibitor saquinavir (SQV) in the setting of CD4+ T-cell depletion to mimic immunodeficiency...The CD4-depleted mice treated with DMBA had significantly increased tumor-free survival and overall survival as well as decreased tumor-volume growth over time when treated with SQV. These data suggest that topical SQV, in the setting of CD4 depletion and high-grade anal dysplasia, can increase tumor-free and overall survival; thus, it may represent a viable topical therapy to decrease the risk of progression of anal dysplasia to anal cancer."

Journal • Preclinical • Anal Carcinoma • Gastrointestinal Cancer • Human Immunodeficiency Virus • Infectious Disease • Oncology • Solid Tumor • CD4

Revamped Role for Approved Drug: Integrative Computational and Biophysical Analysis of Saquinavir's PAD4 Inhibition for Rheumatoid Arthritis. (PubMed, Biochem J) - "These findings underscore SQV's potential as a therapeutic candidate for RA through PAD4 inhibition. Further validation through in-vitro and in-vivo studies is essential to confirm SQV's therapeutic benefits in autoimmune diseases associated with dysregulated citrullination."

Journal • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

In Silico Drug Repurposing Endorse Amprenavir, Darunavir and Saquinavir to Target Enzymes of Multidrug Resistant Uropathogenic E. Coli. (PubMed, Indian J Microbiol) - "Combination or sole application of Amprenavir, Darunavir and Saquinavir to MDR-UPEC infections may leads to cure and inhibition of mortality. The online version contains supplementary material available at 10.1007/s12088-024-01282-x."

Journal • Human Immunodeficiency Virus • Infectious Disease

Novel combinatorial approach: Harnessing HIV protease inhibitors to enhance amphotericin B's antifungal efficacy in cryptococcosis. (PubMed, PLoS One) - "The scarcity and the prohibitive cost of this regimen urge the use of fluconazole as an alternative, leading to increased rates of treatment failure and relapses...Five PIs (ritonavir, atazanavir, saquinavir, lopinavir, and nelfinavir) were found to synergistically potentiate the killing activity of AmB against Cryptococcus strains with ƩFICI ranging between 0.09 and 0.5 against 20 clinical isolates...Finally, we evaluated the efficacy of AmB/PIs combinations in the Caenorhabditis elegans model of cryptococcosis, where these combinations significantly reduced the fungal burden of the treated nematodes by approximately 2.44 Log10 CFU (92.4%) compared to the untreated worms and 1.40 Log10 ((39.4%) compared to AmB alone. The cost-effectiveness and accessibility of PIs in resource-limited geographical areas compared to other antifungal agents, such as flucytosine, make them an appealing choice for combination therapy."

Journal • Human Immunodeficiency Virus • Infectious Disease

Evaluation of the Combinational Therapy of Atazanavir and Saquinavir with Azole Antifungals against Candida auris (ASM Microbe 2024) - "Atazanavir and saquinavir displayed remarkable in vitro synergistic activity with itraconazole and posaconazole against all tested C. auris isolates. The reduction ranged from 93% to 99%, generating log10 colony forming unit (CFU) reductions of 1.15, 0.85, 2.04, and 1.44, respectively. Altogether, the data indicate that atazanavir and saquinavir are potent azole chemo-sensitizing agents that merit further investigation."

Candidiasis • Human Immunodeficiency Virus • Infectious Disease