Ledipasvir (GS-5885) / Gilead - LARVOL DELTA

RhoJ promotes the progression of clear cell renal cell carcinoma via the TNF-α/NF-κB axis. (PubMed, Transl Androl Urol) - "Finally, since there are no available drugs targeting RhoJ, the virtual screening was used to identify potential RhoJ inhibitors based on an FDA-approved drug library, which showed that ergotamine, irinotecan, ledipasvir, pazopanib, and avodart were potential RhoJ-targeting drugs. Taken together, our findings provide novel insights into the role of RhoJ and identify available potential drugs for controlling ccRCC."

Journal • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • RHOJ • TNFA

Synthesis and functionalization of azabicyclo[2.2.1]heptanes for medicinal chemistry applications (ACS-Fall 2025) - "These bicyclic frameworks serve as pivotal structural fragments in natural products and pharmaceuticals, exemplified by Ledipasvir—an approved antiviral agent for hepatitis C treatment...Scalability of key transformations was successfully demonstrated, validating these approaches for larger-scale synthesis relevant to medicinal chemistry applications. Future studies will continue refining selectivity and functional group tolerance, aiming at generating structurally diverse, optically pure azanorbornane derivatives to facilitate novel therapeutic discoveries."

Hepatitis C • Hepatology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases

GSH/pH-Responsive Chitosan-PLA Hybrid Nanosystems for Targeted Ledipasvir Delivery to HepG2 Cells: Controlled Release, Improved Selectivity, DNA Interaction, Electrochemical and Stopped-Flow Kinetics Analyses. (PubMed, Int J Mol Sci) - "The dual-responsive LED-PLA@CS NPs allowed controlled tumor-targeted LED delivery with better selectivity and lower off-target toxicity, making LED-PLA@CS NPs interesting candidates for repurposing HCV treatments into safer cancer nanomedicines. Furthermore, this thorough analysis offers useful reference information for comprehending the interaction between drugs and DNA."

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

Sensitive RP-HPLC method with fluorimetric detection for concurrent quantification of emtricitabine, Daclatasvir and Ledipasvir in human urine. (PubMed, Sci Rep) - "Stability assays reveal that the three studied drugs were stable during preparation, injection and storage. The method can be applied for the quantification of the three drugs co-administered to HIV/HCV co-infected patients' urine which aids in therapeutic drug monitoring and dosage adjustment for chronic patients."

Journal • Hepatitis C • Human Immunodeficiency Virus • Infectious Disease • Inflammation

Machine learning-driven docking of diverse DDAs as promising cysteine protease inhibitors targeting Mpox virus. (PubMed, In Silico Pharmacol) - "Our docking simulations identified four DAAs-Paritaprevir (DB09297), Ledipasvir (DB09027), Lenacapavir (DB15673), and Bictegravir (DB11799)-as having particularly strong binding affinities for mpox protease. This research provides a foundational basis for exploring DAAs as potential new treatments for mpox, with future investigations required to fully determine their therapeutic value. The online version contains supplementary material available at 10.1007/s40203-025-00374-w."

Journal • Human Immunodeficiency Virus • Infectious Disease

Identification of novel compounds against Trypanosoma cruzi using AlphaFold structures. (PubMed, Comput Struct Biotechnol J) - "We performed a virtual screening experiment with T. cruzi AlphaFold protein models and a compound collection of more than 30,000 compounds. We tested the top ranked compounds in an in vitro setting, and found two promising candidates for drug repurposing against Chagas disease: pimecrolimus and ledipasvir."

Journal

Trio-Colored Appraisal of Microwave-Assisted Synthesis of Carbon Quantum Dots as a Fluorescence Turn Off Nanoprobe for Analyzing Ledipasvir in Tablets and Rat Feces: Study of Silymarin Impact on Excretion Recovery. (PubMed, Luminescence) - "Our developed fluorometric procedure demonstrated great sensitivity, selectivity, and functionality that outperformed other sophisticated platforms. Thus, the utility of the depicted procedure in pharmaceutical analysis and studying pharmacokinetics aspects is profoundly proven."

Journal • Preclinical

Structural and Mechanistic Insights into the Main Protease (Mpro) Dimer Interface Destabilization Inhibitor: Unveiling New Therapeutic Avenues against SARS-CoV-2. (PubMed, Biochemistry) - "This study identified six highly efficacious antiviral SARS-CoV-2 compounds (WIN-62577, KT185, bexarotene, ledipasvir, diacerein, and simepervir) using structure-based virtual screening of compound libraries against Mpro. Minocycline binds to an allosteric site, revealing residues critical for the loss of protease activity due to destabilization of molecular interactions at the dimeric interface, which are crucial for the proteolytic activity of Mpro. The study suggests that the binding of minocycline to the allosteric site may play a role in Mpro dimer destabilization and direct the rational design of minocycline derivatives as antiviral drugs."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Prevalence of resistance-associated substitutions (RAS) in hepatitis C virus in the Former Soviet Union countries. (PubMed, BMJ Open Gastroenterol) - "The high prevalence of HCV genotypes 1b and 3a in the FSU region and the presence of specific RASs should be considered when determining the most effective treatment regimen for HCV-infected individuals in the FSU countries."

Journal • Hepatitis C • Hepatology • Infectious Disease • Inflammation

Exploring bacterial key genes and therapeutic agents for breast cancer among the Ghanaian female population: Insights from In Silico analyses. (PubMed, PLoS One) - "Subsequently, the bKG-guided top ranked 10 drug molecules Digitoxin, Digoxin, Ledipasvir, Suramin, Ergotamine, Venetoclax, Nilotinib, Conivaptan, Dihydroergotamine, and Elbasvir were identified using molecular docking analysis. The stability of top-ranked three drug-target complexes (Digitoxin-pykA, Digoxin-mdh, and Ledipasvir-pgi) were confirmed through the molecular dynamics simulation studies. Therefore, these findings might be useful resources to the wet-lab researchers for further experimental validation on bacterial therapies against BC."

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

FDA-approved antivirals ledipasvir and daclatasvir downregulate the Src-EPHA2-Akt oncogenic pathway in colorectal and triple-negative breast cancer cells. (PubMed, Biomed Pharmacother) - "At the molecular level, these direct-acting antivirals inhibit the phosphorylation of Akt and the ephrin type A receptor 2 (EPHA2) by destabilizing a Src-EPHA2 complex, although they do not affect the general kinase activity of Src. Thus, LDV and DCV could be effective drugs for Src-associated cancers without the inherent toxicity of classical Src inhibitors."

FDA event • IO biomarker • Journal • Breast Cancer • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Hepatitis C • Hepatology • Infectious Disease • Oncology • Solid Tumor • Triple Negative Breast Cancer • PD-L1

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

Discovery of Bacterial Key Genes from 16S rRNA-Seq Profiles That Are Associated with the Complications of SARS-CoV-2 Infections and Provide Therapeutic Indications. (PubMed, Pharmaceuticals (Basel)) - "Then, we detected bKG-guided top-ranked eight drug molecules (Bemcentinib, Ledipasvir, Velpatasvir, Tirilazad, Acetyldigitoxin, Entreatinib, Digitoxin, and Elbasvir) by molecular docking. Finally, the binding stability of the top-ranked three drug molecules (Bemcentinib, Ledipasvir, and Velpatasvir) against three receptors (hldD, mlaA, and lptD) was investigated by computing their binding free energies with molecular dynamic (MD) simulation-based MM-PBSA techniques, respectively, and was found to be stable. Therefore, the findings of this study could be useful resources for developing a proper treatment plan against bacterial co-/super-/secondary-infection in SARS-CoV-2 infections."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

FBXO8 is a novel prognostic biomarker in different molecular subtypes of breast cancer and suppresses breast cancer progression by targeting c-MYC. (PubMed, Biochim Biophys Acta Gen Subj) - "These findings illuminate the novel role of FBXO8 as a prognostic and therapeutic target across different molecular subtypes of breast cancer. Finally, through the utilization of virtual screening and Molecular Dynamics simulations, we successfully identified two FDA-approved medications, Ledipasvir and Paritaprevir, that demonstrated robust binding capabilities and interactions with FBXO8."

Biomarker • IO biomarker • Journal • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • FBXW7 • IL10 • IL6 • MYC • NOTCH1 • PTEN

Network transmission of hepatitis C genotype 2c and 4d in men who have sex with men in Cape Town, South Africa (EASL-ILC 2023) - "All HIV positive patients were virally suppressed and 90% (n = 27) have completed HCV treatment: 38% (n = 10 with SOF/Daclatasvir), 33% (n = 5 with SOF/Ribavirin); 19% (n = 9 with SOF/Ledipasvir) and 10% (n = 3 with SOF/Velpatasvir), with a 100% SVR rate. Demonstrated for the first time in South Africa, phylogenetic analysis strongly suggests a network transmission of 2 HCV GT subtypes in MSM in Cape Town. This data emphasizes the need for an important policy focus in the local viral hepatitis strategy for a micro-elimination, targeted education, prevention, and treatment program within this key population. Treatment outcomes to date are excellent."

Fibrosis • Hepatitis C • Hepatology • Human Immunodeficiency Virus • Infectious Disease • Inflammation

In silico Antivirus Repurposing and its Modification to Organoselenium Compounds as SARS-CoV-2 Spike Inhibitors. (PubMed, Pak J Biol Sci) - "The best-modified ligand was chosen by analyzing the ADME-Tox property, RMSD value and binding energy value. <b></b> The best three unmodified ligands, Ombitasvir, Elbasvir and Ledipasvir, have a binding energy value of -15.8065, -15.3842 and -15.1255 kcal mol¹, respectively and the best three modified ligands ModL1, ModL2 and ModL3 has a binding value of -15.6716, -13.9489 and -13.2951 kcal mol¹, respectively with an RMSD value of 1.7109 Å, 2.3179 Å and 1.7836 Å."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

In silico molecular study of hepatitis B virus X protein as a therapeutic target. (PubMed, J Biomol Struct Dyn) - "The analysis of relative binding free energy through MM/GBSA for molecular dynamic simulation results revealed binding energy -9.9 kcal/mol for SC75741, -11 kcal/mol for Punicalagin, and -10.1 kcal/mol for Ledipasvir. These results elucidate the possible use of these compounds in the research for targeting HBx.Communicated by Ramaswamy H. Sarma."

Journal • Fibrosis • Gastroenterology • Gastrointestinal Cancer • Hepatitis B • Hepatocellular Cancer • Hepatology • Immunology • Infectious Disease • Inflammation • Liver Cirrhosis • Oncology • Solid Tumor

Wolbachia Ferrochelatase as a potential drug target against filarial infections. (PubMed, J Mol Graph Model) - "We identified four drug candidates; Nilotinib, Ledipasvir, 3-benzhydryloxy-8-methyl-8-azabicyclo[3.2.1]octane, and 2-(4-Amino-piperidin-1-yl)-ethanol as potential small molecules inhibitors as they could compete with the enzyme's natural substrate (Protoporphyrin IX) for active pocket binding. This prevents the worm from receiving the heme molecule from Wolbachia for their growth and survival, resulting in their death. This study which involved targeting enzymes in biosynthetic pathways of the parasitic worms' endosymbiont (Wolbachia), has proven to be an alternative therapeutic option leading to the discovery of new drugs, which will help facilitate the elimination of parasitic infections."

Journal • Infectious Disease

Cheminformatics-Based Study Identifies Potential Ebola VP40 Inhibitors. (PubMed, Int J Mol Sci) - "A total of 23 approved drugs, including doramectin, glecaprevir, velpatasvir, ledipasvir, avermectin B1, nafarelin acetate, danoprevir, eltrombopag, lanatoside C, and glycyrrhizin, among others, were also predicted to have potential anti-EBOV activity and can be further explored so that they may be repurposed for EVD treatment. Molecular dynamics simulations coupled with molecular mechanics Poisson-Boltzmann surface area calculations corroborated the stability and good binding affinities of the complexes (-46.97 to -118.9 kJ/mol). The potential lead compounds may have the potential to be developed as anti-EBOV drugs after experimental testing."

Journal • Hematological Disorders • Infectious Disease

Structure-based computational screening of 470 natural quercetin derivatives for identification of SARS-CoV-2 M inhibitor. (PubMed, PeerJ) - "The binding affinity, stability, and free energy results for 382 and Mpro were better than those of the native ligand and the standard inhibitors ledipasvir and cobicistat. The conclusion of our study was that compound 382 has the potential to inhibit SARS-Cov-2 Mpro. However, further investigations such as in-vitro assays are recommended to confirm its in-silico potency."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Release Enhancement by Plasticizer Inclusion for Amorphous Solid Dispersions Containing High T Drugs. (PubMed, Pharm Res) - "The use of plasticizers represents a potential new strategy to increase drug loading in ASDs for high T compounds with a low tendency to crystallize and may help improve a major limitation of ASD formulations, namely the high excipient burden."

Journal

The Association between miRNAs in Persistent HCV Infection and mRNA of Hepatocellular Carcinoma (APASL 2023) - "Clinical studies have confirmed that long-term HCVinfected patients respond poorly to the NS5A inhibitors ledipasvir and daclatasvir. The main cause of HCC is that HCV inhibits the expression of hsa-miR-215-5p, and it has a significant effect on survival, suggesting that hsa-miR-215-5p may play an essential role in virusrelated liver cancer. These findings provide a precision strategy to monitor liver cancer caused by chronic hepatitis C, reduce the incidence of liver cancer in chronic HCV-infected patients, and achieve the goal of precision medicine. 608"

Gastrointestinal Cancer • Hepatitis C • Hepatocellular Cancer • Hepatology • Infectious Disease • Oncology • Solid Tumor • CDH1 • FZD5 • MIR10B • MIR215 • PMAIP1

Novel HCV Genotype 4d Infectious Systems and Assessment of Direct-Acting Antivirals and Antibody Neutralization. (PubMed, Viruses) - "The efficacies of NS3/4A protease- and NS5A- inhibitors against genotypes 4a and 4d were similar, except for ledipasvir, which is less potent against 4d. Compared to 4a, the 4d(C5A)-13m virus was more sensitive to neutralizing monoclonal antibodies AR3A and AR5A, as well as 4a and 4d patient plasma antibodies. In conclusion, we developed the first genotype 4d infectious culture system enabling DAA efficacy testing and antibody neutralization assessment critical to optimization of DAA treatments in the clinic and for vaccine design to combat the HCV epidemic."

Journal • Hepatitis C • Hepatology • Infectious Disease • Inflammation

Current insights and molecular docking studies of the drugs under clinical trial as rdrp inhibitors in COVID-19 treatment. (PubMed, Curr Pharm Des) - "The drug repurposing approach provides a new avenue in COVID-19 treatment."

Journal • Human Immunodeficiency Virus • Infectious Disease • Influenza • Novel Coronavirus Disease • Respiratory Diseases • IL6

Effectiveness of Remdesivir in Comparison with Five Approved Antiviral Drugs for Inhibition of RdRp in Combat with SARS-CoV-2. (PubMed, Iran J Sci Technol Trans A Sci) - "Also, the results show that the number of H-bonds and contacts and ∆G interactions between the protein and ligand in the Remdesivir complex is less than those of other complexes. According to the given data which shows the tendency of binding with RdRp for Paritaprevir, Simeprevir, Glecaprevir, and Ledipasvir and Elbasvir is more than Remdesivir and due to the fact that these five drugs have a high tendency to bind to other targets in the SARS-CoV-2, the use of Remdesivir as an antiviral drug in the treatment of COVID-19 should be considered more sensitively."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases