Olysio (simeprevir) / J&J, Medivir - LARVOL DELTA

Development of a novel iCasp9 kill switch for safer cell therapies (ESGCT 2024) - "Furthermore, when SIM-iCasp9-expressing tumour cells are implanted into mice, administration of a single dose of simeprevir led to complete tumour regression. Kill switches such as this are helping to drive these next generation cell therapies to the clinic by improving safety to the patients."

Hematological Malignancies • Solid Tumor • CASP9

Drug Repurposing: In Vitro Evaluation of Simeprevir as a Novel Antiviral Drug Against Severe Fever With Thrombocytopenia Syndrome Virus. (PubMed, J Med Virol) - "Simeprevir, Novobiocin, and Levofloxacin hydrochloride demonstrated significant antiviral activity (EC50: 0.009774, 25.12, and 46.30 μM, respectively) with minimal cytotoxicity. Although these three small-molecule drugs show promise for SFTSV treatment, further in vivo studies are necessary to confirm their safety and optimize their structures. Our findings highlight the potential of drug repurposing as a strategy for developing effective therapies against emerging viral infections."

Journal • Preclinical • Hematological Disorders • Infectious Disease • Thrombocytopenia

Molecular chameleons adaptability in target binding (ACS-Fall 2025) - "Due to their flexible structure, these modalities often behave like molecular chameleons, which have been shown to be important for bioavailability since they can change their conformations based on the polarity of their solvation environment.In this presentation, we will showcase our exploration of the conformational adaptability in target binding of three known molecular chameleons, paritaprevir, grazoprevir, and simeprevir, by evaluating their experimentally determined microcrystal electron diffraction (MicroED) structures, solution-state conformations from NMR spectroscopy, and target-bound structures, in molecular docking studies. This offers a framework for optimizing drug selectivity and improving therapeutic efficacy. Furthermore, it provides a pathway toward rationalizing drug optimization for molecular chameleons, facilitating the safe use of these inhibitors while broadening their potential in antiviral and cancer-target applications."

Infectious Disease • Respiratory Diseases

Molecular chameleons adaptability in target binding. (PubMed, Struct Dyn) - "In this study, we explore the conformational adaptability in target binding of the three known molecular chameleons, paritaprevir, grazoprevir, and simeprevir, by docking their experimental crystal structures, solution conformations, and target-bound structures into multiple protein targets, including human drug transporters associated with drug-drug interactions and COVID-19 related proteins. Our findings reveal that the macrocyclic core conformational class, or "chameleonic group," determines the overall pharmacophore conformations and influences the conformational changes required for binding to various proteins. These insights provide a pathway toward rationalizing drug optimizations for molecular chameleons as well as offering specific guidance for improving Hepatitis C virus nonstructural protein 3/4A inhibitors, including providing a starting point for their COVID-19 repurposing and cancer therapy."

Journal • Hepatitis C • Infectious Disease • Novel Coronavirus Disease • Oncology

Drug Repurposing for Targeting ISL LIM Homeobox 2 in Treatment of Endometriosis: A Computational Study. (PubMed, Int J Fertil Steril) - "Although these six drugs appear to be promising candidates for modulating endometriosis, Ivermectin is more likely to effectively inhibit ISL2."

Journal • Endometriosis • Gynecology • Women's Health

Identification of nsp16 inhibitors of SARS -CoV-2, SARS -CoV-1 and MERS-CoV from FDA-approved drugs using in silico and in vitro methods. (PubMed, Biomed Pharmacother) - "Nilotinib and simeprevir interacted with nsp16 protein of all three coronaviruses, viz., SARS-CoV-2, SARS-CoV-1, and MERS-CoV, suggesting their potential to act as pan-coronavirus inhibitors. The drugs inhibited the virus with IC50 values ranging between 8.34 and 36.1 µM when tested against a clinical isolate of SARS-CoV-2 in cell culture."

FDA event • Journal • Preclinical • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Reviving the Past: Targeting FliN in Uropathogenic Escherichia coli for Next-Gen UTI Therapies (ASM Microbe 2025) - "Based on the interactional analysis, binding energy, and constant inhibition, three drugs, namely Olysio, Telithromycin, and Rucaparib, were designated as the best inhibitors. Further in vitro and in vivo studies are needed to confirm its anti-bacterial activity and use as a potential antimicrobial drug against urinary tract infections caused by E. coli."

Infectious Disease • Nephrology

Reviving the Past: Targeting FliN in Uropathogenic Escherichia coli for Next-Gen UTI Therapies (ASM Microbe 2025) - "Based on the interactional analysis, binding energy, and constant inhibition, three drugs, namely Olysio, Telithromycin, and Rucaparib, were designated as the best inhibitors. Further in vitro and in vivo studies are needed to confirm its anti-bacterial activity and use as a potential antimicrobial drug against urinary tract infections caused by E. coli."

Infectious Disease • Nephrology

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

The Pattern of Renal Involvement in Relapsing Cryoglobulinemic Vasculitis After Successful Sustained Viral Response by Direct-Acting Antiviral Treatments (ERA 2025) - "From 2015 to 2020, patients received the following DAA protocols: Sofosbuvir + either Simeprevir, Daclatasvir, Ledipasvir, or Ribavirin. Relapsing cases were associated with more aggressive clinical and pathological renal manifestations. Membranoproliferative & Crescentic GN were the most common glomerular lesions in relapsing cases."

Complement-mediated Rare Disorders • Hepatitis B • Hepatology • Human Immunodeficiency Virus • Infectious Disease • Inflammation • Nephrology • Pain • Renal Disease • Rheumatology • Vasculitis

A dose exploration and dose expansion phase Ib/II study to evaluate oral HTMC0435 tablets in combination with platinum and etoposide in patients with extensive stage small cell lung cancer (ChiCTR) - P1/2 | N=74 | Recruiting | Sponsor: The First Affiliated Hospital of Zhengzhou University; Shanghai Yidian Pharmaceutical Technology Development Co., Ltd.

New P1/2 trial • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Efficacy and safety of HTMC0435 combination with temozolomide in relapsed extensive-stage small-cell lung cancer (ES-SCLC): A phase Ib/II study. (ASCO 2025) - P1b/2 | "This combination of HTMC0435 and TMZ showed promising anti-tumor activity and manageable safety both in platinum-sensitive and platinum-resistant SCLC patients. Clinical trial information: NCT05728619. Research Sponsor: Shanghai Yidian Pharma."

Clinical • P1/2 data • Anemia • Leukopenia • Lung Cancer • Neutropenia • Oncology • Small Cell Lung Cancer • Solid Tumor • Thrombocytopenia

An eco-friendly chemometrics assisted UV spectrophotometric method for simultaneous determination of sofosbuvir, simeprevir and ledipasvir in pharmaceuticals. (PubMed, BMC Chem) - "Greenness assessment confirmed the method's environmental advantages with superior scores in multiple sustainability metrics (Analytical GREEnness metric, AGREE: 0.75; Modified Green Analytical Procedure Index, MOGAPI: 78; RGB12 whiteness score: 94.2) compared to conventional chromatographic techniques (AGREE: 0.63-0.65, MOGAPI: 66-72, RGB12: 76.9-83.3). These findings establish the proposed method as a rapid, sensitive, and eco-friendly alternative for routine quality control of these critical hepatitis C drugs."

Journal • Hepatitis C • Infectious Disease • Inflammation

SWITCH-1: Switching Regimen in Treating Cirrhotic HCV GT1b Subjects (clinicaltrials.gov) - P2 | N=138 | Completed | Sponsor: Humanity and Health Research Centre | Recruiting ➔ Completed | Trial completion date: Dec 2022 ➔ Oct 2024 | Trial primary completion date: Oct 2022 ➔ Oct 2024

Trial completion • Trial completion date • Trial primary completion date • Hepatitis C • Hepatology • Infectious Disease • Inflammation

Elongation factor Tu promotes the onset of periodontitis through mediating bacteria adhesion. (PubMed, NPJ Biofilms Microbiomes) - "Furthermore, we first found that simeprevir, an FDA-approved drug, binds to the "Barrel-like adhesion domain" of EF-Tu and effectively inhibits the protein's surface adhesion and secretory pathways. Simeprevir showed the ability to inhibit dental plaque formation and provided prevention and treatments for periodontitis."

Journal • Dental Disorders • Periodontitis

Exploring the potential of direct-acting antivirals against Chikungunya virus through structure-based drug repositioning and molecular dynamic simulations. (PubMed, Comput Biol Med) - "Our findings suggest repurposing hepatitis C virus (HCV) antivirals, specifically Simeprevir (SIM) and voxilaprevir (VOX), could be effective against CHIKV...To validate the results of our computational study, we evaluated the antiviral efficacy of SIM and VOX in vitro, both as monotherapies and in combination with ribavirin (RIBA)...Furthermore, the synergistic effects suggest that combining SIM and VOX with RIBA may provide a more effective therapeutic strategy than using either drug alone. Further research is necessary to optimize treatment protocols and improve outcomes for patients affected by CHIKV."

Journal • Chikungunya • Hepatitis C • Hepatology • Infectious Disease • Inflammation

HEPATITIS C VIRUS GENOTYPE 1A TREATMENT IN DIALYSIS PATIENTS: SINGLE CENTER OBSERVATIONAL STUDY (ISN-WCN 2025) - "In this single-centre observational study, our objective is to evaluate the efficacy and safety of Sofosbuvir+ Daclatasvir (S+D) and Sofosbuvir+ Velpatasvir (S+V) in the treatment of HCV genotype 1a in dialysis patients...Parameters S+D (n=45) S+V (n=25) P value Mean age (years) 44 (32-52) 52 (46-59) 0.24 Male 33 (73%) 19 (76%) 0.967 Diabetes 11 (24%) 11 (44%) 0.09 Hypertension 41 (91%) 23 (92%) 0.89 CAD 1 (2%) 2 (8%) 0.26 Comorbidities(stroke, cirrhosis, peripheral vascular disease) 1 (2%) 3 (12%) 0.09 Parameters S+D (n=45) S+V (n=25) P Value Remission (SVR) 43 (96%) 24 (96%) 0.942 Treatment failure 2 (4%) 1 (4%) 0.93 Need to decrease Sofosbuvir 8 (17%) 0 (0%) 0.03 Need to use PPI 26 (57%) 16 (64%) 0.63 Mean duration if HCV detection after dialysis initiation (months) 8 (4.5-10) 9 (6-12.75) 0.89 Anti HCV before starting therapy 41 (91%) 19 (76%) 0.08 Anti HCV after treatment 36 (80%) 15 (60%) 0.7 Mean viral load 416784 (84621-1550000) 261631 (6582.75- 909981.2) 0.21 HBV..."

Clinical • Observational data • Anemia • Anorexia • Cardiovascular • Chronic Kidney Disease • Complement-mediated Rare Disorders • Diabetes • Diabetic Nephropathy • Fibrosis • Glomerulonephritis • Hematological Disorders • Hepatitis C • Hepatology • Hypertension • Infectious Disease • Inflammation • Lupus Nephritis • Metabolic Disorders • Nephrology • Pain • Peripheral Arterial Disease • Renal Disease

EARLY NONINVASIVE EVALUATION OF LIVER FIBROSIS AFTER HEPATITIS C TREATMENT: THE IMPACT OF INFLAMMATION. (PubMed, Arq Gastroenterol) - "The evaluation of hepatic elastography by the ARFI method before and after (6 - 9 months) successive treatment of hepatitis C in responders and non-responders led to the conclusion that the reduction of elastography parameters seems to be related to a decrease in hepatic inflammation rather than a reduction in fibrosis per se."

Journal • Fibrosis • Gastroenterology • Hepatitis C • Hepatology • Immunology • Infectious Disease • Inflammation • Liver Cirrhosis

The Pattern of Renal Involvement in Relapsing Cryoglobulinemic Vasculitis After Successful Sustained Viral Response by Direct-Acting Antiviral Treatments (ACR Convergence 2024) - "From 2015 to 2020, patients received the following DAA protocols: Sofosbuvir + either Simeprevir, Daclatasvir, Ledipasvir, or Ribavirin. Relapsing cases were associated with more aggressive clinical and pathological renal manifestations. Membranoproliferative & Crescentic GN were the most common glomerular lesions in relapsing cases. There was significant global sclerosis, vascular and tubulointerstitial involvement in the relapsing cases."

Complement-mediated Rare Disorders • Hepatitis B • Hepatology • Human Immunodeficiency Virus • Immunology • Infectious Disease • Inflammation • Nephrology • Pain • Renal Disease • Rheumatology • Vasculitis

Simeprevir induces ferroptosis through β-TrCP/Nrf2/GPX4 axis in triple-negative breast cancer cells. (PubMed, Biomed Pharmacother) - "Moreover, SIM administration into the xenografts formed by MDA-MB-231 dramatically suppressed the tumor progression by inducing ferroptosis in vivo. Collectively, this finding reveals that SIM may serve as a competitive therapeutic strategy to inhibit TNBC."

Journal • Breast Cancer • Hepatitis C • Hepatology • Infectious Disease • Oncology • Solid Tumor • Triple Negative Breast Cancer • GPX4

An environmentally sustainable synchronous spectrofluorimetric method coupled with second derivative signal processing for simultaneous determination of velpatasvir and simeprevir in pharmaceutical and plasma samples. (PubMed, Spectrochim Acta A Mol Biomol Spectrosc) - "Velpatasvir and simeprevir are two direct acting antivirals that are often used in combination with sofosbuvir to treat HCV infections. The method was very sensitive, with lower detection limits of 1.11 ng/mL and 25.40 ng/mL, and quantification limits of 3.36 ng/mL and 76.96 ng/mL for velpatasvir and simeprevir, respectively.The method was effectively used to determine velpatasvir and simeprevir simultaneously in their pure forms, pharmaceutical dosage forms, and human plasma with no interference. The suggested technique was additionally evaluated for its eco-friendliness through the utilization of the Analytical GREEnness (AGREE) and Green Analytical Procedure Index (GAPI) evaluation metrics, revealing that the method is indeed sustainable."

Journal • Hepatitis C • Infectious Disease

PREINCUBATION-DEPENDENT INHIBITION OF ORGANIC ANION TRANSPORTING POLYPEPTIDE 2B1. (PubMed, Eur J Pharm Sci) - "Therefore, we studied the effect of preincubation on OATP2B1 inhibition with five known OATP2B1 inhibitors (atorvastatin, erlotinib, ezetimibe, ticagrelor and simeprevir) in HEK293 cells transiently overexpressing OATP2B1. In conclusion, preincubation resulted in inhibitor- and substrate-dependent inhibition of OATP2B1. These results support the conclusion that to reduce the risk of false negative DDI prediction, preincubation should be considered also in OATP2B1 inhibition assays."

Journal • SLCO2B1

Synchronous spectrofluorimetry and chemometric modeling: A synergistic approach for analyzing simeprevir and daclatasvir, with application to pharmacokinetics evaluation. (PubMed, Spectrochim Acta A Mol Biomol Spectrosc) - "Moreover, the proposed models have been applied to determine the pharmacokinetics of simeprevir and daclatasvir, providing valuable insights into their distribution and elimination patterns. Overall, the study demonstrates the effectiveness of synchronous spectrofluorimetry coupled with multivariate calibration optimized by firefly algorithms in accurately determining and quantifying simeprevir and daclatasvir in HCV antiviral treatment, offering potential applications in pharmaceutical formulation analysis and pharmacokinetic studies for these drugs."

Journal • PK/PD data • Hepatitis C • Hepatology • Infectious Disease • Inflammation

HCV antiviral drugs have the potential to adversely perturb the maternal-fetal communication axis through inhibition of CYP3A7 DHEA-S oxidation. (PubMed, Drug Metab Dispos) - "Furthermore, paritaprevir, asunaprevir, simeprevir, danoprevir, and glecaprevir all had observed half-maximal inhibitory concentrations between the range of 10-20 µM, which is physiologically relevant in comparison to the K of DHEA-S oxidation (reported to be between 5 to 20 µM). We discovered that five HCV antivirals inhibited DHEA-S metabolism by CYP3A7, and paritaprevir inactivated the enzyme. Our studies demonstrate the potential threat these drugs pose to proper fetal development."

Journal • Hepatitis C • Hepatology • Infectious Disease • Inflammation • CYP3A7

Update on monkeypox virus infection: Focusing current treatment and prevention approaches. (PubMed, Fundam Clin Pharmacol) - "This review highlights the pathogenesis of the virus, disease manifestations, drugs, and vaccines that are being used and those under pipeline for the treatment and prevention of Mpox."

Journal • Review • Infectious Disease • Novel Coronavirus Disease