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Mechanisms of Hepatitis C Virus Clearance by Interferon and Ribavirin Combination
Published in Satya Prakash Gupta, Cancer-Causing Viruses and Their Inhibitors, 2014
Srikanta Dash, Partha K. Chandra, Kurt Ramazan, Robert F. Garry, Luis A. Balart
NS3 protease is a bifunctional enzyme that contains serine protease in the N-terminal 180 amino acid residues. The search for small molecule inhibitors led to the identification of the first-generation protease inhibitors: telaprevir and boceprevir. Additional second generation NS3/4A protease inhibitors simeprevir (TMC435), faldaprevir, and danoprevir are in the clinical stage of development. Preliminary studies using them in naïve patients suggested that each of these second-generation protease inhibitors produces a better antiviral response than the first-generation protease inhibitors.
Success stories of AI in drug discovery - where do things stand?
Published in Expert Opinion on Drug Discovery, 2022
Kit-Kay Mak, Madhu Katyayani Balijepalli, Mallikarjuna Rao Pichika
Deep Chemical Expression (DeepCE), a novel DL model to predict the interactions between genes and dugs was developed by Ohio State University, USA. It has predicted that 10 drugs: Faldaprevir, Alisporivir, NIM811 (antiviral for hepatitis C); Anidulafungin, Oteseconazole (antifungals); Voclosporin, Cyclosporine (immunosuppressants); Ceftobiprole medocaril (antibiotics), Valspodar (anticancer drugs); and Evacetrapib (cardiovascular drug) can be repurposed for the treatment of COVID-19 [93]. Of these (as of June 24, 2021), three drugs (Alisporivir, Voclosporin, and Cyclosporine) are being tested in clinical trials to assess and confirm their efficacy in COVID-19 patients. The rationale behind repurposing these three drugs for COVID-19 treatment is that they are inhibitors of cyclophilin enzyme, which plays a vital role in the life cycle of coronaviruses [94–96]. The details of the clinical trials on these three drugs are summarized in Table S1. All the studies are open-label, and the results are yet to be released. Alisporivir is in phase 2 clinical trial (NCT04608214) in which the patients are yet to be recruited. It is a randomized, proof of concept, and single-center study to evaluate the efficacy, safety, and tolerability in hospitalized adult COVID-19 patients.
An update on recent developments in the search for hepatitis C virus therapies with pan-genotypic efficacy
Published in Expert Opinion on Investigational Drugs, 2019
Guglielmo Borgia, Riccardo Scotto, Antonio Riccardo Buonomo
In a phase 2 trial, the efficacy of RDV was evaluated together with the NS5B deleobuvir (DBV) and the NS3 inhibitor faldaprevir (FDV) [11]. Enrolled patients (n = 36) were randomized to receive FDV 120 mg QD + DBV 600 or 400 mg BID + RDV 200 mg QD ± RBV. Available results of 24 patients who completed 12-week posttreatment follow-up showed an overall SVR12 rate of 96%. Three patients had a virologic breakthrough. One breakthrough was related to NS5A RAS (Q30L + Y93H) and NS5B RAS (A421V). A total of two discontinuations occurred. Most serious ADRs were not related to treatment. Frequent ADRs were nausea, fatigue, diarrhea, rash, anemia, insomnia, abdominal pain, vomiting, flatulence, pruritus, and tremors.