New developments in small molecular compounds for anti-hepatitis C virus (HCV) therapy

Tong, Jing; Wang, Youwei; Lu, Yuanan

doi:10.1631/jzus.b1100120

Cited by 13 publications

(7 citation statements)

References 129 publications

(106 reference statements)

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“…Although it appears that biologics are favored over small molecule drugs, there are also several studies indicating that small molecule drugs were more successful than biologics, implying that the drug chemistry that carries the least risk is dependent on the disease [ 5 , 6 ]. For hepatitis C specifically, the tests and assays used in the development of the new drugs more accurately assess small molecule drugs and their targets; therefore these drugs are favored over biologics [ 23 ]. Small molecule drugs may be superior to biologics for hepatitis C simply based on what has previously been approved, but there are other factors, such as the drug targets as well as the available testing systems, that may have a larger impact on the outcome of the drug and that must be analyzed in conjunction with the drug chemistry.…”

Section: Discussionmentioning

confidence: 99%

Clinical Trial Risk in Hepatitis C: Endpoint Selection and Drug Action

Tillie

Parker

Feld

2016

Canadian Journal of Gastroenterology and Hepatology

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Background and Aims. This study analyzed the risk of clinical trial failure of new drugs for hepatitis C between January 1998 and January 2015. Methods. Hepatitis C drug development trials that were in phases I–III of clinical trial testing were obtained from the publicly accessible clinical trial repository and other publicly available databases. Drug compounds were excluded from the study if they began their phase I testing before 1998, if they were not industry sponsored, or if they treated secondary complications of hepatitis C. Clinical trial success rates were analyzed in comparison to industry expectations. Further analysis was conducted on the molecule classifications, the mechanisms of action, and the trial endpoints. Results. One hundred and twenty-three unique drug compounds were found to fulfill the inclusion criteria, eight of which had FDA approval. The overall cumulative pass rate for hepatitis C drugs was 20%, which is double the industry expectation rate. Viral inhibitor small molecule drugs significantly reduced the risk of drug failure during clinical trials compared to other mechanisms of action. Conclusion. On average, one in every five drugs that began clinical testing will be approved for market. Viral inhibitor small molecule drugs are the most promising and hold the least risk.

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Section: Discussionmentioning

confidence: 99%

Clinical Trial Risk in Hepatitis C: Endpoint Selection and Drug Action

Tillie

Parker

Feld

2016

Canadian Journal of Gastroenterology and Hepatology

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“…It is reported that there are 120-180 million hepatitis C virus (HCV) carriers around the world, with the worldwide prevalence estimated at 3% (Shepard et al, 2005;Tong et al, 2012). Chronic hepatitis C is considered to be a major cause of liver disease, including progressive liver fibrosis, cirrhosis, and hepatocellular carcinoma (Hoofnagle, 2002;Shepard et al, 2005;Thomas and Seeff, 2005;Micallef et al, 2006;Zhu et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Association between serum vitamin D and severity of liver fibrosis in chronic hepatitis C patients: a systematic meta-analysis

Luo

Ling

et al. 2014

J. Zhejiang Univ. Sci. B

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Abstract:To conduct a systematic review of group studies assessing the association of serum vitamin D status with the severity of liver fibrosis in chronic hepatitis C patients using meta-analysis. The relevant research literatures were identified by searching PubMed and EMBASE databases prior to October 2013 with no restrictions. We included group studies that reported odds ratio (OR) estimates with 95% confidence intervals (CIs) or a mean with standard deviation (SD) for the association between serum vitamin D status and the severity of liver fibrosis in chronic hepatitis C patients. Approximately 8321 participants from several countries were included in this analysis. Six studies on serum vitamin D status and the severity of liver fibrosis were included in this meta-analysis. ORs with 95% CIs were extracted from four studies and the pooled ORs were 0.866 (95% CI, 0.649 to 1.157). The means with SDs were extracted from three studies and the pooled means were −0.487 (95% CI, −0.659 to −0.315). There was statistically significant heterogeneity among the mean data extracted studies (P=0.029; I 2 =71.8%) but not among the OR data extracted studies (P=0.061; I 2 =55.6%). Finally, results from the mean data extracted studies suggest that lower serum vitamin D is a risk factor for the severity of liver fibrosis in chronic hepatitis C patients. However, there is no conclusive evidence on this association because of inconsistencies between the OR data extracted studies and the mean data extracted studies.

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“…Grazoprevir is a directly acting antiviral drug that inhibits the protease of the HCV [25]. Telaprevir, Boceprevir and Grazoprevir are approved inhibitors of PLPro of HCV [26][27][28][29]. Other notable compounds that were found to inhibit the SARS-CoV-2 PLPro include GRL0617, Mycophenolic acid and GRL0667 (Table 1).…”

Section: Discussionmentioning

confidence: 99%

In search of drugs to counter the countermeasures of SARS-CoV-2 in evading host’s innate immune defense: a Molecular modeling approach.

Choudhury

Borah

Mazumder³

et al. 2020

Preprint

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The coronaviruses (CoV), including SARS-CoV, MERS-CoV and the novel SARS-CoV-2, evade the host innate immunity employing Papain-like protease (PLPro). PLPro performs deubiquitination and deISGylation of host proteins and signaling molecules, and thus antagonize the host’s innate immune response. Thus, PLPro is a promising drug target against SARS-CoV-2. The present study employs molecular modeling approaches to determine potential of different compounds as inhibitors of the PLPro. The results demonstrated that drugs like Stallimycin, and known PLPro inhibitors including Telaprevir, Grazoprevir and Boceprevir, were highly potent in inhibiting the enzyme. In addition, several plant-derived polyphenols were also found to be potent inhibitors.

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New developments in small molecular compounds for anti-hepatitis C virus (HCV) therapy

Cited by 13 publications

References 129 publications

Clinical Trial Risk in Hepatitis C: Endpoint Selection and Drug Action

Clinical Trial Risk in Hepatitis C: Endpoint Selection and Drug Action

Association between serum vitamin D and severity of liver fibrosis in chronic hepatitis C patients: a systematic meta-analysis

In search of drugs to counter the countermeasures of SARS-CoV-2 in evading host’s innate immune defense: a Molecular modeling approach.

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