tegobuvir (GS 9190) / Gilead - LARVOL DELTA

Inhibition of hepatitis E virus replication by FDA-Approved RdRp inhibitors (APASL 2024) - "In this study, we screened some well-known RdRp inhibitor molecules, notably, favipiravir, sofosbuvir, remdesivir, filibuvir, and tegobuvir. Therefore, favipiravir has an additive effect when used with sofosbuvir. Therefore, we propose that favipiravir is a promising anti-HEV drug that can be used in combination with sofosbuvir."

Hepatology • Inflammation

Inhibition of HEV Replication by FDA-Approved RdRp Inhibitors. (PubMed, ACS Omega) - "In this study, we screened some well-known RdRp inhibitor molecules, notably, favipiravir, sofosbuvir, remdesivir, filibuvir, and tegobuvir. Therefore, favipiravir has an additive effect when used with sofosbuvir. Therefore, we propose that favipiravir is a promising anti-HEV drug that can be used in combination with sofosbuvir."

FDA event • Journal • Hepatology • Inflammation

Bioinformatics-based investigation on the genetic influence between SARS-CoV-2 infections and idiopathic pulmonary fibrosis (IPF) diseases, and drug repurposing. (PubMed, Sci Rep) - "Then, we suggested the cHubGs-guided top-ranked 10 candidate drug molecules (Tegobuvir, Nilotinib, Digoxin, Proscillaridin, Simeprevir, Sorafenib, Torin 2, Rapamycin, Vancomycin and Hesperidin) for the treatment against SARS-CoV-2 infections with IFP diseases as comorbidity. Molecular docking results suggested that our proposed drug molecules would be more effective compare to the already published drug molecules. Thus, the findings of this study might be played a vital role for diagnosis and therapies of SARS-CoV-2 infections with IPF disease as comorbidity risk."

Journal • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases • CXCR4 • IRF4 • NLRP3 • TNFAIP3 • TNFAIP6 • VCAM1

Identification of host genomic biomarkers from multiple transcriptomics datasets for diagnosis and therapies of SARS-CoV-2 infections. (PubMed, PLoS One) - "This analysis resulted in the identification of top-ranked ten drug agents, including Nilotinib, Tegobuvir, Digoxin, Proscillaridin, Olysio, Simeprevir, Hesperidin, Oleanolic Acid, Naltrindole and Danoprevir. Finally, we investigated the binding stability of the top-ranked three drug molecules Nilotinib, Tegobuvir and Proscillaridin with the three top-ranked proposed receptors (AURKA, AURKB, OAS1) by using 100 ns MD-based MM-PBSA simulations and observed their stable performance. Therefore, the findings of this study might be useful resources for diagnosis and therapies of SARS-CoV-2 infections."

Biomarker • Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • AURKA • AURKB • ER • IL6 • MEIS1 • MIR106B • MIR20A • MIR20B • MIR93 • MMP2 • PBX1 • STAT4

Drug Repurposing Strategy (DRS): Emerging Approach to Identify Potential Therapeutics for Treatment of Novel Coronavirus Infection. (PubMed, Front Mol Biosci) - "The methodologies involved in drug repurposing can be categorized into three groups such as drug-oriented, target-oriented and disease or therapy-oriented depending on the information available related to quality and quantity of the physico-chemical, biological, pharmacological, toxicological and pharmacokinetic property of drug molecules. This review focuses on drug repurposing strategy applied for existing drugs including Remdesivir, Favipiravir, Ribavirin, Baraticinib, Tocilizumab, Chloroquine, Hydroxychloroquine, Prulifloxacin, Carfilzomib, Bictegravir, Nelfinavir, Tegobuvir and Glucocorticoids etc to determine their effectiveness toward the treatment of COVID-19."

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

In silico prediction of SARS-CoV-2 main protease and polymerase inhibitors: 3D-Pharmacophore modelling. (PubMed, J Biomol Struct Dyn) - "The present study used HEX and AutoDock Vina softwares to predict the affinity of about 100 medicinal structures toward the active site of 3-chymotrypsin-like protease (3Clpro) and RNA-dependent RNA polymerase (RdRp), separately...In addition to compound 45, tipranavir (28) and atazanavir (26) as FDA-approved HIV protease inhibitors were tightly interacted with the active site of SARS-CoV-2 main protease as well. Based on pharmacophore modelling, a good structural pattern for potent candidates against SARS-CoV-2 main enzymes is suggested. Re-tasking or taking inspiration from the structures of tegobuvir and tipranavir can be a proper approach toward coping with the COVID-19 in the shortest possible time and at the lowest cost."

Journal • Hepatitis C Virus • Hepatology • Human Immunodeficiency Virus • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Structure-based drug repurposing for targeting Nsp9 replicase and spike proteins of severe acute respiratory syndrome coronavirus 2. (PubMed, J Biomol Struct Dyn) - "Our findings suggest Conivaptan and Tegobuvir as potential therapeutic agents against SARS-CoV-2. Further in vitro and in vivo validation and evaluation are warranted to establish how these drug compounds target the Nsp9 replicase and spike proteins."

Journal • Hepatitis C Virus • Hepatology • Infectious Disease • Novel Coronavirus Disease • Tuberculosis

Potential Drugs Targeting Early Innate Immune Evasion of SARS-Coronavirus 2 via 2'-O-Methylation of Viral RNA. (PubMed, Viruses) - "Here we provide a computational basis for drug repositioning or de novo drug development based on three differential traits of the intermolecular interactions of the SARS-CoV-2-specific nsp16/nsp10 heterodimer, namely: (1) the S-adenosyl-l-methionine-binding pocket of nsp16, (2) the unique "activating surface" between nsp16 and nsp10, and (3) the RNA-binding groove of nsp16. After molecular dynamics calculations of the stability of the binding modes of high-scoring nsp16/nsp10-drug complexes, we considered their pharmacological overlapping with functional modules of the virus-host interactome that is relevant to the viral lifecycle, and to the clinical features of COVID-19. Some of the predicted drugs (e.g., tegobuvir, sonidegib, siramesine, antrafenine, bemcentinib, itacitinib, or phthalocyanine) might be suitable for repurposing to pharmacologically reactivate innate immune restriction and antagonism of SARS-CoV-2 RNAs lacking 2'-O-methylation."

Journal • Novel Coronavirus Disease • Respiratory Diseases

SARS-CoV-2 and SARS-CoV: Virtual Screening of Potential inhibitors targeting RNA-dependent RNA polymerase activity (NSP12). (PubMed, J Med Virol) - "Eight compounds (Nilotinib, Saquinavir, Tipranavir, Lonafarnib, Tegobuvir, Olysio, Filibuvir and Cepharanthine) were selected for binding free energy calculations based on virtual screening and docking scores. Eight compounds (Nilotinib, Saquinavir, Tipranavir, Lonafarnib, Tegobuvir, Olysio, Filibuvir and Cepharanthine) were selected for binding free energy calculations based on virtual screening and docking scores. All eight compounds can combine well with NSP12-NSP7-NSP8 in the crystal structure, providing drug candidates for the treatment and prevention of COVID-19 and SARS."

Journal • Infectious Disease • Novel Coronavirus Disease

Quantifying antiviral activity optimizes drug combinations against hepatitis C virus infection. (PubMed) - Proc Natl Acad Sci U S A - "From the calculated IIP of 15 anti-HCV drugs from different classes [telaprevir, danoprevir, asunaprevir, simeprevir, sofosbuvir (SOF), VX-222, dasabuvir, nesbuvir, tegobuvir, daclatasvir, ledipasvir, IFN-α, IFN-λ1, cyclosporin A, and SCY-635], we found that the nucleoside polymerase inhibitor SOF had one of the largest potentials to inhibit viral replication events. Our quantification analysis clearly indicated an advantage of triple-DAA treatments over double-DAA treatments, with triple-DAA treatments showing enhanced antiviral activity and a significantly lower probability for drug resistance to emerge at clinically relevant drug concentrations. Our framework provides quantitative information to consider in designing multidrug strategies before costly clinical trials."

Journal • Biosimilar • Hepatitis C Virus • Immunology

Design, synthesis, and structure-activity relationships of novel imidazo[4,5-c]pyridine derivatives as potent non-nucleoside inhibitors of hepatitis C virus NS5B. (PubMed, Bioorg Med Chem) - "The efforts to optimize the antiviral potency and reduce the treatment side effects with respect to genotype 1b resulted in the discovery of compound 3, which exhibited an EC of 1.163 nM and a CC >200 nM in a cell-based HCV replicon system assay. Additionally, testing for inhibition of the hERG channel showed a marked improvement over tegobuvir and the pharmacokinetic properties of compound 3 indicated that it was worthy of further investigation as a non-nucleoside inhibitor of HCV NS5B polymerase."

Journal • Biosimilar • Hepatitis C Virus • Immunology • Infectious Disease

A study of response-guided duration of combination therapy with GS-9190, GS-9256, Pegasys and Copegus in previously untreated subjects with genotype 1 chronic hepatitis C (clinicaltrials.gov) - P2, N=320; Sponsor: Gilead; Active, not recruiting; Completion date: Oct 2015 -> Jan 2017.

Trial completion date • Hepatitis C Virus

GS 5885 administered concomitantly with GS-9451, tegobuvir and ribavirin (RBV) in chronic genotype 1 hepatitis C Virus (HCV) infection (clinicaltrials.gov) - P2, N=120; Recruiting -> Active, not recruiting

Enrollment closed • Hepatitis C Virus

High sustained virologic response rate in treatment-naïve HCV genotype 1A and 1B patients treated for 12 weeks with an interferon-free all-oral quad regimen: Interim results (EASL 2012) - Presentation time: 19.04.2012, 09:00-18:00; P2, N=141; 26 of 27 (96%) achieved SVR4; Viral breakthrough occurred only in GT1a patients (8/55); Two patients terminated early; IL28B status did not appear to correlate with SVR4 or breakthrough

P2 interim data • Hepatitis C Virus

Effect of early viral kinetics on Interferon-g inducible protein-10 in patients given an all-oral anti-hepatitis C virus regimen (CROI 2013) - Abstract#703; Sponsor: Gilead; P2, N=124; NCT01353248; "All patients receiving anti-viral therapy had a rapid decline in HCV RNA, but overall response varied. Over the first 2 weeks of treatment, a bi-phasic pattern of IP-10 decline was observed"

P2 data • Hepatitis C Virus

High SVR12 with 16 weeks of tegobuvir and GS-9256 with peginterferon-alfa 2a and ribavirin in treatment-naïve genotype 1 HCV patients (EASL 2012) - Presentation time: 19.04.2012, 16:00-18:00; P2, N=323; Using LLOQ at Week 2 to shorten treatment duration to 16 weeks results in an SVR4 rate of 98% in treatment-naïve, genotype 1 HCV patients treated with tegobuvir + GS-9256 + PEG + RBV

P2 data • Hepatitis C Virus

Antiviral efficacy of the NS3 protease inhibitor, GS-9451, non-nucleoside NS5B inhibitor, tegobuvir, and pegylated interferon plus ribavirin in treatment-naïve genotype 1 hepatitis C infected patients (EASL 2013) - Presentation time: 26.04.2013, 16:00-18:00; Abstract 68; P2, N=239; NCT01353248; Sponsor: Gilead; “The regimen was well tolerated with 4-6% of patients experiencing a serious adverse event…addition of GS-9451 to a PEG/RBV regimen results in improved SVR12 rates in treatment-naïve, genotype 1 HCV patients relative to PEG/RBV.”

P2 data • Hepatitis C Virus