IDX 184 / Merck (MSD) - LARVOL DELTA

Dynamics and binding affinity of nucleoside and non-nucleoside inhibitors with RdRp of SARS-CoV-2: a molecular screening, docking, and molecular dynamics simulation study. (PubMed, J Biomol Struct Dyn) - "The results of molecular docking and MD simulation studies reveal that IDX184 is a stable molecule and forms strong interactions with the key amino acids and shows high binding affinity towards RdRp. Hence, IDX184 may also be considered as a potential inhibitor of RdRp after clinical study.Communicated by Ramaswamy H. Sarma."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Dual targeting of RdRps of SARS-CoV-2 and the mucormycosis-causing fungus: an in silico perspective. (PubMed, Future Microbiol) - "The results reveal a comparable binding affinity of sofosbuvir, galidesivir, ribavirin and remdesivir compared with the physiological nucleotide triphosphates against R. oryzae RdRp as well as the SARS-CoV-2 RdRp as reported before. Additionally, other compounds such as setrobuvir, YAK, IDX-184 and modified GTP compounds 2, 3 and 4 show potential calculated average binding affinities against R. oryzae RdRp. The present in silico study suggests the dual inhibition potential of the recommended drugs and compounds against SARS-CoV-2 and R. oryzae RdRps."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

INSIGHTS INTO THE BIOLOGICAL IMPACT OF COVID-19 AND ITS VACCINES ON HUMAN HEALTH. (PubMed, Saudi J Biol Sci) - "The availability of FDA-approved anti-RdRp drugs (Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir) as potent drugs against SARS-CoV-2 that tightly bind to its RdRp may aid in the treatment of patients and reduce the risk of the mysterious new form of COVID-19 viral infection. RdRp inhibitors, such as remdesivir (an anti-Ebola virus experimental drug) and favipiravir (an anti-influenza drug), inhibit RdRp and thus slow the progression of COVID-19 and associated clinical symptoms, as well as significantly shorten recovery time. Molnupiravir, an orally active RdRp inhibitor and noval broad spectrum antiviral agent, is an isopropyl pro-drug of EIDD-1931 for emergency use...Top seeds for antiviral treatments with high potential to combat the SARS-CoV-2 strain include guanosine derivatives (IDX-184), setrobuvir, and YAK. The goal of this review is to compile scattered information on available COVID-19 vaccines and other treatments for protecting the human body..."

Journal • Review • Cardiovascular • Gastrointestinal Disorder • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Antiviral drugs against severe acute respiratory syndrome coronavirus 2 infection triggering the coronavirus disease-19 pandemic. (PubMed, Tzu Chi Med J) - "The nucleotide inhibitors such as sofosbuvir, ribavirin, galidesivir, remdesivir, favipiravir, cefuroxime, tenofovir, and hydroxychloroquine (HCHL), setrobuvir, YAK, and IDX-184 were found to be effective in binding to SARS-CoV-2 RNA-dependent RNA polymerase. From the antimalarial and anti-inflammatory category, chloroquine and its derivative HCHL have already been approved by the U.S. Food and Drug Administration for emergency treatment of SARS-CoV-2 infection. The other drugs such as favipiravir and lopinavir/ritonavir under the antiviral category, the angiotensin-converting enzyme 2 (the renin-angiotensin system inhibitors), remdesivir (RNA polymerase inhibitor) from antiviral category, cepharanthine from anti-inflammatory category, etc., have been pointed based on the previous literature published. Besides, the assessment of the drug repositioning candidates with the related targets is also significant for the viral mitigation."

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

Intracellular metabolism and potential cardiotoxicity of a β-D-2'-C-methyl-2,6-diaminopurine ribonucleoside phosphoramidate that inhibits hepatitis C virus replication. (PubMed, Nucleosides Nucleotides Nucleic Acids) - "Imaging data of drug treated human cardiomyocytes was found to be most useful in determining toxicity potential as no obvious beating rate change was observed for IDX-184 up to 50 µM up at 48 h. However, with BMS-986094 and DAPN-PD at 10 µM changes to both beat rate and rhythm were noted."

Journal • Hepatitis C Virus • Hepatology • Infectious Disease

Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir against SARS-CoV-2 RNA dependent RNA polymerase (RdRp): A molecular docking study. (PubMed, Life Sci) - "The availability of FDA-approved anti-RdRp drugs can help treat patients and reduce the danger of the mysterious new viral infection COVID-19. The drugs mentioned above can tightly bind to the RdRp of the SARS-CoV-2 strain and thus may be used to treat the disease. No toxicity measurements are required for these drugs since they were previously tested prior to their approval by the FDA."

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

SARS-CoV-2 RNA dependent RNA polymerase (RdRp) targeting: An in silico perspective. (PubMed, J Biomol Struct Dyn) - "The results show the effectiveness of Sofosbuvir, Ribavirin, Galidesivir, Remdesivir, Favipiravir, Cefuroxime, Tenofovir, and Hydroxychloroquine, in binding to SARS-CoV-2 RdRp. Additionally, Setrobuvir, YAK, and IDX-184, show better results, while four novel IDX-184 derivatives show promising results in attaching to the SARS-CoV-2 RdRp...The availability of a punch of FDA-approved anti-viral drugs can help us in this mission, aiming to reduce the danger of COVID-19. The compounds 2 and 3 may tightly bind to the SARS-CoV-2 RdRp and so may be successful in the treatment of COVID-19."

Journal • Immunology • Novel Coronavirus Disease

Idenix shares rise on promising mid-stage hep C data (Reuters) - Shares of Idenix rose 16% after the company reported positive mid-stage trial data of its hepatitis C drug IDX184

Sales projection • Hepatitis C Virus

Q2 '11 results (Idenix) - IDX 184 / Idenix; Anticipated P2b interim data release in Q4 '11 in combination with pegylated interferon & ribavirin

Anticipated P2b Interim data • Hepatitis C Virus • None

Idenix Pharmaceuticals provides update on IDX184 and IDX19368 development programs (Idenix) - "Idenix...announced...not to continue its clinical development program for IDX184...phase IIb testing for the treatment of...HCV infection, or to continue its development of IDX19368...for which the Company had previously filed an IND but had not initiated patient dosing."

Discontinued • Hepatitis C Virus

Q3 2012 Results (Idenix) - Anticipated interim results from P2b trial (IDX184+pegylated interferon+ribavirin combination) at AASLD, (Nov 13, 2012)

Anticipated P2b data • Hepatitis C Virus

IDX184 in combination with peginterferon alfa-2a and ribavirin for two weeks in treatment-naive patients with chronic hepatitis C (Antivir Ther) - P=NA, N=81; PMID: 23439365; "...HCV RNA changes from baseline...proportion of patients achieving undetectable viral load (<15 IU/ml)...were -2.7±1.3 (13%), -4.0±1.7 (50%), -4.2±1.9 (50%), -4.1±1.2 (40%), -4.3±1.5 (29%) and -3.7±1.2 (25%) for the 50mg QD (once daily), 50mg BID (twice daily), 100mg QD, 150mg QD, 100mg BID and 200mg QD IDX184 doses respectively."

Clinical data • Hepatitis C Virus

Idenix announces positive clinical data for HCV drug candidates IDX184 and IDX719 (Idenix) - P2b, N=31; NCT01371604; Of 9 of 31 pts who completed 12-week PegIFN/RBV extended treatment phase, 100% of pts (4/4) in the 100 mg arm and 80% of pts (4/5) in the 50 mg arm achieved SVR 4 weeks after the completion of treatment; Idenix announced positive data from a three-day POC study evaluating IDX719, treatment-naïve, genotype 1, 2, 3 or 4 HCV-infected pts; Detailed findings on IDX719 expected to be presented at a scientific meeting in H2 2012

P2b data • Hepatitis C Virus

J.P. Morgan Healthcare Conference (Idenix) - IDX-184 / Idenix; Anticipated removal of partial clinical hold in 2012 for HCV; Anticipated combining with DAAs for regimen and initiate P2b trials in 2012 for HCV; Anticipated collaboration in 2012 for HCV

Anticipated clinical plan • Anticipated corporate collaboration • Anticipated P2b trial initiation • Hepatitis C Virus

Idenix announces removal of the partial clinical hold on HCV nucleotide inhibitor, IDX184 (Idenix) - Idenix announced that it has received notification from the U.S. FDA that the partial clinical hold on IDX184 has been removed and that the company's 12-week P2b study evaluating IDX184 in combination with pegylated interferon & ribavirin (PegIFN/RBV) may continue

FDA update • Hepatitis C Virus

Anti-HCV, nucleotide inhibitors, repurposing against COVID-19. (PubMed, Life Sci) - "The present study presents a perfect model for COVID-19 RdRp enabling its testing in silico against anti-polymerase drugs. Besides, the study presents some drugs that previously proved its efficiency against the newly emerged viral infection."

Journal