Invirase (saquinavir) / Roche - LARVOL DELTA

FDA-approved drug library screen identifies antidepressants, antimicrobials, anti-COPD, and anti-CVD agents as blockers of NLRP3 inflammasome and sepsis in a sex-dependent manner. (PubMed, bioRxiv) - "Various classes of drugs, such as antidepressants (Fluoxetine, Duloxetine), antihypertensives (Irbesartan, amlodipine, nebivolol), antidiabetics (Rosiglitazone), β-adrenergic agonists (Salmeterol), antimalarials (Mefloquine), antifungals (Azoles, ciclopirox), and antivirals (Saquinavir, Remdesivir), were identified as potent blockers of either priming or assembly of NLRP3 inflammasome. Mice treated with LPS-priming blockers showed a sex-specific increase in survival rate in the mouse model of LPS-induced mortality, validating the in vitro screen. Further studies in primary human cells and in vivo disease models are needed to assess the repurposing and therapeutic relevance of identified drugs."

FDA event • Journal • Alzheimer's Disease • Asthma • Chronic Obstructive Pulmonary Disease • CNS Disorders • Diabetes • Genetic Disorders • Gout • Immunology • Infectious Disease • Inflammatory Arthritis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Movement Disorders • Novel Coronavirus Disease • Obesity • Parkinson's Disease • Pulmonary Disease • Respiratory Diseases • Rheumatology • Septic Shock • NLRP3

Targeting RSV F and N Proteins: A Computational Approach to Identify Effective Antivirals (RSVVW 2026) - "For the F protein, we selected three ligands: Venetoclax, Nilotinib, and Saquinavir, with binding energies of which had a docking score of -9.20 kcal/mol, -11.56 kcal/mol, and -6.35 kcal/mol, and corresponding Ki values of 971.93 nM, 3.37 nM, and 22.00 µM, respectively. For the N protein, the selected ligands were Dutasteride, Conivaptan, and Ergotamine, with docking scores of -8.07 kcal/mol, -7.41 kcal/mol, and -8.59 kcal/mol, and Ki values of 1.21 µM, 3.71 µM, and 507.71 nM, respectively...Additionally, the Protein-Ligand Interaction Profiler revealed hydrophobic interactions between the ligands and the receptors. Our study proposes a suitable and innovative approach to combat RSV infection, warranting further validation through in vitro methods to fully establish efficacy."

Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

Repurposing amide-based drugs unveils inhibition mechanisms of plasmodium falciparum Plasmepsin V enzymatic activity for antimalarial therapy. (PubMed, Bioorg Chem) - "In this work, we investigated whether three approved amide-based drugs favipiravir, 5-fluorouracil (5-FU), and saquinavir could inhibit catalytic activity of PfPlmV. Favipiravir binds at the periphery of the cleft without engaging the catalytic dyad and therefore behaves as a weak, non-inhibitory binder. The insights of interaction-structure-inhibitory activity obtained from this study may guide repurposing strategies to develop selective potent inhibitors/antimalarial agents targeting PfPlmV."

Journal • Infectious Disease • Malaria

Saquinavir induces pyroptosis through the OTUD5-JAK1-GSDME axis in hepatocellular carcinoma. (PubMed, Free Radic Biol Med) - "Pyroptosis is a newly defined form of programmed cell death characterized by plasma membrane perforation, release of cellular contents, and a robust inflammatory response, thereby sensitizing tumors to existing anticancer therapies. Furthermore, the combination of SAQ with sorafenib, a first-line therapeutic agent for HCC, exhibited synergistic antitumor activity both in vitro and in the nude mouse model. These findings not only identify SAQ as a novel pyroptosis-inducer, but also clarify the critical role of the OTUD5-JAK1-GSDME axis in resisting pyroptosis, which may further provide experimental evidence and potential new strategies for treating HCC."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • CASP3 • GSDME • JAK1 • OTUD5

Repurposing of FDA-Approved Drugs to Identify Potential NS2B/NS3 Protease Inhibitors against Dengue Virus: In Silico and In Vitro Evaluation. (PubMed, Acta Trop) - "The three hits, Simeprevir, Saquinavir, and Dolutegravir of were subsequently evaluated for their cytotoxicity and antiviral activity in Vero cells, using MTT and infectivity-based assays, respectively. This study reflects on the potential of Dolutegravir as a dengue protease inhibitor and also indicates the efficacy of drug repurposing as a drug discovery strategy in the paradigm of antiviral discovery. Dolutegravir was identified as a potential candidate against DENV-2, and additional research is needed with molecular dynamics, mechanistic inquiry, and in vivo support investigation."

FDA event • Journal • Preclinical • Dengue Fever • Infectious Disease

Vitamin C Conjugates in Biomedicine: A Comprehensive Exploration with Drugs, Polymers, Proteins, and Peptides. (PubMed, Mini Rev Med Chem) - "Vitamin C-drug conjugates, including derivatives of diclofenac, aspirin, and naproxen, have demonstrated improved transport across the blood-brain barrier via SVCT-mediated uptake, offering potential for the treatment of neurodegenerative disorders. Similarly, conjugation with antivirals such as saquinavir improves oral absorption and systemic bioavailability by bypassing efflux mechanisms...Protein conjugates, utilizing carriers such as HSA, BSA, and β-lactoglobulin, facilitate systemic transport, while peptide conjugates leverage the antioxidant activity of vitamin C in conjunction with peptide-based targeting, providing synergistic benefits in cosmetics and dermatology. Collectively, these studies highlight vitamin C conjugation as a versatile platform for precision medicine and targeted therapy."

Journal • CNS Disorders • Dermatology • Oncology

Deciphering virus host interaction analysis to unravel core virus network signatures and computational drug repurposing for cervical cancer. (PubMed, Comput Biol Med) - "Ten candidate drugs, Pleconaril, Pirodavir, Saquinavir, Delavirdine, and Tipranavir for VE7_HPV16 and Beclabuvir, Velpatasvir, Paritaprevir, Odalasvir, and Ledipasvir for VE6_HPV18, were predicted to exhibit high binding affinities with their respective viral targets. Additionally, Molecular Dynamics (MD) simulations were performed to examine the stability of the protein-ligand complexes and evaluate the role of SLiMs-containing regions in modulating virus-host interactions. Collectively, this comprehensive analysis of the virus-host network identified key HPV protein targets and proposed antiviral drug candidates to impede viral contributions to cervical carcinogenesis."

Journal • Cervical Cancer • Infectious Disease • Oncology • Solid Tumor

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