Cyclophilin Inhibitors for Hepatitis C Therapy

Membreno, Fernando E.; Espinales, Jennifer C.; Lawitz, Eric

doi:10.1016/j.cld.2012.09.008

Cited by 22 publications

(22 citation statements)

References 58 publications

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“…CypA inhibitors such as cyclosporine A (CsA) have been shown to inhibit the replication of HIV, HCV, influenza virus, CoV, HBV, HSV, human cytomegalovirus (HCMV), VSV, vaccinia virus (VV) and human papillomavirus (HPV) [105][106][107][108][109][110][111][112][113][114] . Alisporivir (Debio-025) and SCY-635, both CsA analogues, have shown antiviral activity against HCV in vivo and are currently in combination with other anti-HCV compounds in various clinical trials 115,116 . ER α-glucosidases I and II play a critical role in glycosylation of viral proteins 102 .…”

Section: Targeting Common Host-factors Used For Viral Replicationmentioning

confidence: 99%

Antiviral drug discovery: broad-spectrum drugs from nature

et al. 2015

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, but cannot be converted to PDF. You must view these files (e.g. movies) online.Scheme 1_(structures 1-5)_named.cdx Scheme 2_(structures 6-8)_named.cdx Scheme 3_(structure 9)_named.cdx Scheme 4_(structure 10)_named.cdx Scheme 5_ (structures 11-12) The development of drugs with broad-spectrum antiviral activities is a long pursued goal in drug discovery. It has been shown that blocking co-opted host-factors abrogates the replication of many viruses, yet the development of such host-targeting drugs has been met with skepticism mainly due to toxicity issues and poor translation to in vivo models. With the advent of new and more powerful screening assays and prediction tools, the idea of a drug that can efficiently treat a wide range of viral infections by blocking specific host functions has rebloomed. Here we critically review the state-of-the-art in broad-spectrum antiviral drug discovery. We discuss putative targets and treatment strategies, taking particular focus on natural products as promising starting points for antiviral lead development.

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Section: Targeting Common Host-factors Used For Viral Replicationmentioning

confidence: 99%

Antiviral drug discovery: broad-spectrum drugs from nature

et al. 2015

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“…Whereas the results from these 3 studies suggest that SCY-635 or NIM811 could restore human immune responses to IFN treatment, they likely have less relevance in the IFN-free regimen era. The role of cycophilin inhibitors in hepatitis C and other liver diseases has been recently reviewed [37]; future studies could elucidate their role as an addition to oral treatment regimens [38]. At the current time, no evidence supports the use of either of these agents for chemoprophylaxis.…”

Section: Host Target Agentsmentioning

confidence: 99%

Postexposure prophylaxis after hepatitis C occupational exposure in the interferon-free era

Hughes

Henderson

2016

Current Opinion in Infectious Diseases

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Purpose of review Healthcare personnel are at risk for occupational exposures to bloodborne pathogens. Primary prevention remains the first line of defense, but secondary prevention measures known to be effective should be implemented when percutaneous exposures occur. Hepatitis C virus (HCV) is a major infectious cause of liver-related morbidity and mortality. Chronic HCV treatment has changed dramatically, with many all-oral directly acting anti-HCV antiviral (DAA) regimens now available. Evidence for the use of DAAs as post-exposure prophylaxis (PEP) after occupational exposures to HCV is summarized here. Recent findings Little new evidence supports the use of antivirals in acute HCV infection. Several preliminary studies have examined the use of DAAs or host target agents (HTAs) in chronic HCV treatment. Effective HCV PEP requirements likely include pan-genotypic activity and a high barrier to resistance. One investigational DAA has shown promising results as an efficacious option for all genotypes in chronic HCV treatment and may ultimately represent a potential HCV PEP agent. Summary Insufficient supporting data exist to endorse the use of DAAs for PEP after HCV occupational exposures; additional studies examining efficacy, duration, and cost-effectiveness are needed. Development of more oral drugs possessing a high barrier of resistance and equal activity against all HCV genotypes is anticipated.

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“…Cyclophilin inhibitors have been shown to have broad antiviral affects in clinical trials for hepatitis C (Membreno et al, 2013). The mechanism of action appears to involve an affect upon host protein-folding chaperones used in viral polypeptide function.…”

Section: Host-targeting Antiviralsmentioning

confidence: 99%

Chronic hepatitis B: A wave of new therapies on the horizon

2015

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This year marks the 50th anniversary of the discovery of the Australia antigen (Blumberg, Alter and Visnich, 1965), which in 1968 was identified to be the hepatitis B virus (HBV) surface antigen. Even though several antiviral medications have been in use for the management of chronic HBV infection for more than 20 years, sustained clearance of HBsAg, similar to the sustained viral response (SVR) or cure in chronic hepatitis C (HCV), occurs in only a minority of treated patients. Moreover, even after 10 years of effective suppression of HBV viremia with current therapy, there is only a 40-70% reduction in deaths from liver cancer. Recent success in developing antivirals for hepatitis C that are effective across all genotypes has renewed interest in a similar cure for chronic HBV infection. In this article, we review a wave of newly identified drug targets, investigational compounds and experimental strategies that are now under clinical evaluation or in preclinical development. The paper forms part of a symposium in Antiviral Research on “An unfinished story: From the discovery of the Australia antigen to the development of new curative therapies for hepatitis B.”

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Cyclophilin Inhibitors for Hepatitis C Therapy

Cited by 22 publications

References 58 publications

Antiviral drug discovery: broad-spectrum drugs from nature

Antiviral drug discovery: broad-spectrum drugs from nature

Postexposure prophylaxis after hepatitis C occupational exposure in the interferon-free era

Chronic hepatitis B: A wave of new therapies on the horizon

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