Systematic review produced by the EPPI-Centre in 2015.This systematic review aimed to evaluate the effect of HAART and ARV monotherapy on liver disease progression and liver-related mortality in individuals co-infected with HIV and hepatitis C, including in patients with haemophilia.

CD81 plays a central role in a variety of physiological and pathological processes. Recent structural analysis of CD81 indicates that it contains an intramembrane cholesterol-binding pocket and that interaction with cholesterol may regulate a conformational switch in the large extracellular domain of CD81. Therefore, CD81 possesses a potential cholesterol-sensing mechanism; however, its relevance for protein function is thus far unknown. In this study we investigate CD81 cholesterol sensing in the context of its activity as a receptor for hepatitis C virus (HCV). Structure-led mutagenesis of the cholesterol-binding pocket reduced CD81–cholesterol association but had disparate effects on HCV entry, both reducing and enhancing CD81 receptor activity. We reasoned that this could be explained by alterations in the consequences of cholesterol binding. To investigate this further we performed molecular dynamic simulations of CD81 with and without cholesterol; this identified a potential allosteric mechanism by which cholesterol binding regulates the conformation of CD81. To test this, we designed further mutations to force CD81 into either the open (cholesterol-unbound) or closed (cholesterol-bound) conformation. The open mutant of CD81 exhibited reduced HCV receptor activity, whereas the closed mutant enhanced activity. These data are consistent with cholesterol sensing switching CD81 between a receptor active and inactive state. CD81 interactome analysis also suggests that conformational switching may modulate the assembly of CD81–partner protein networks. This work furthers our understanding of the molecular mechanism of CD81 cholesterol sensing, how this relates to HCV entry, and CD81's function as a molecular scaffold; these insights are relevant to CD81's varied roles in both health and disease.

Withdrawn by Author.

Title: New Drug Combo Helps Hard-to-Treat Hepatitis C
Category: Health News
Created: 8/27/2013 4:36:00 PM
Last Editorial Review: 8/28/2013 12:00:00 AM

Title: Liver Damage From Hepatitis C More Widespread Than Thought
Category: Health News
Created: 8/27/2015 12:00:00 AM
Last Editorial Review: 8/27/2015 12:00:00 AM

Title: Test All U.S. Adults for Hepatitis C, Expert Panel Says
Category: Health News
Created: 8/27/2019 12:00:00 AM
Last Editorial Review: 8/28/2019 12:00:00 AM

Title: Hepatitis C Infection Can Kill, But Less Than a Third of Patients Get Treatment
Category: Health News
Created: 8/10/2022 12:00:00 AM
Last Editorial Review: 8/10/2022 12:00:00 AM

Patent holder and pharma major Gilead, announced voluntary licences with seven generic drug manufacturers in India to s

Indian drug maker, Cipla has announced that it has released the generic version of Hepatitis C drug, Sofosbuvir in India.The drug will be marketed under

US pharmaceutical giant Gilead has obtained a patent for its Hepatitis C drug from India. This patent could potentially stop affordable copies reaching millions of people in other countries.

Berlin, May 5: Several drugs approved for the treatment of hepatitis C viral infection have been identified as potential candidates against COVID-19 caused by the SARS-CoV-2 coronavirus, according to a study based on extensive calculations using supercomputer simulations.

Compounds of Formula I, including pharmaceutically acceptable salts, as well as compositions containing these compounds, have activity against hepatitis C virus (HCV) and may be useful in treating those infected with HCV:

Health authorities urge more than 500 patients of a dental clinic in Far North Queensland to be tested for HIV and hepatitis as the clinic is investigated over its infection control practices.

Systematic review produced by the EPPI-Centre in 2015.This systematic review aimed to evaluate the effect of HAART and ARV monotherapy on liver disease progression and liver-related mortality in individuals co-infected with HIV and hepatitis C, including in patients with haemophilia.

Withdrawn by Author.

There’s been a lot of attention given to the new antirviral drugs which target Hepatitis C - partly because of the burden of infection of the disease, and the lack of a treatment that can be made easily accessible to around the world, and partly because of the incredible cost of a course of treatment. But a new article on BMJ talks about the...

Rafael Simó
Sep 1, 1996; 19:998-1000
Short Report

Combination therapy with interferon beta-1b plus lopinavir-ritonavir and ribavirin appears to improve symptoms and shorten hospital stays for people with mild to moderate COVID-19.

The quinoline MK-571 is the most commonly used inhibitor of multidrug resistance protein-1 (MRP-1) but was originally developed as a cysteinyl leukotriene receptor 1 (CysLTR1) antagonist. While studying the modulatory effect of MRP-1 on anti-hepatitis C virus (HCV) direct acting-antivirals (DAA) efficiency, we observed an unexpected anti-HCV effect of compound MK-571 alone. This anti-HCV activity was characterized in Huh7.5 cells stably harboring a subgenomic genotype 1b replicon. A dose-dependent decrease of HCV RNA levels was observed upon MK-571 administration, with an EC₅₀ of 9±0.3 μM and a maximum HCV RNA level reduction of approximatively 1 Log₁₀. MK-571 also reduced the replication of the HCV full-length J6/JFH1 model in a dose-dependent manner. However, probenecid and apigenin homodimer (APN), two specific inhibitors of MRP-1, had no effect on HCV replication. In contrast, the CysLTR1 antagonists SR2640 increased HCV-SGR RNA levels in a dose-dependent manner, with a maximum increase of 10-fold. In addition, a combination of natural CysLTR1 agonist (LTD4) or antagonists (zafirlukast, cinalukast, and SR2640) with MK-571 completely reversed its antiviral effect, suggesting its anti-HCV activity is related to CysLTR1 rather to MRP-1 inhibition. In conclusion, we showed that MK-571 inhibits HCV replication in hepatoma cell cultures by acting as a CysLTR1 receptor antagonist, thus unraveling a new host-virus interaction in the HCV life cycle.

Title: FDA Panel Urges Approval of Hepatitis C Drug
Category: Health News
Created: 4/28/2011 11:01:00 AM
Last Editorial Review: 4/28/2011 12:00:00 AM

Title: FDA Panel Backs 2 Hepatitis C Drugs
Category: Health News
Created: 4/29/2011 11:01:00 AM
Last Editorial Review: 4/29/2011 12:00:00 AM

Title: Opioid Crisis Means More Newborns With Hepatitis C, But Few Get Tested
Category: Health News
Created: 5/2/2018 12:00:00 AM
Last Editorial Review: 5/2/2018 12:00:00 AM

Immune-competent animal models for the hepatitis C virus (HCV) are nonexistent, impeding studies of host-virus interactions and vaccine development. Experimental infection of laboratory rats with a rodent hepacivirus isolated from Rattus norvegicus (RHV) is a promising surrogate model due to its recapitulation of HCV-like chronicity. However, several aspects of rat RHV infection remain unclear, for instance, how RHV evades host adaptive immunity to establish persistent infection. Here, we analyzed the induction, differentiation, and functionality of RHV-specific CD8 T cell responses that are essential for protection against viral persistence. Virus-specific CD8 T cells targeting dominant and subdominant major histocompatibility complex class I epitopes proliferated considerably in liver after RHV infection. These populations endured long term yet never acquired antiviral effector functions or selected for viral escape mutations. This was accompanied by the persistent upregulation of programmed cell death-1 and absent memory cell formation, consistent with a dysfunctional phenotype. Remarkably, transient suppression of RHV viremia with a direct-acting antiviral led to the priming of CD8 T cells with partial effector function, driving the selection of a viral escape variant. These data demonstrate an intrinsic abnormality within CD8 T cells primed by rat RHV infection, an effect that is governed at least partially by the magnitude of early virus replication. Thus, this model could be useful in investigating mechanisms of CD8 T cell subversion, leading to the persistence of hepatotropic pathogens such as HCV.

IMPORTANCE Development of vaccines against hepatitis C virus (HCV), a major cause of cirrhosis and cancer, has been stymied by a lack of animal models. The recent discovery of an HCV-like rodent hepacivirus (RHV) enabled the development of such a model in rats. This platform recapitulates HCV hepatotropism and viral chronicity necessary for vaccine testing. Currently, there are few descriptions of RHV-specific responses and why they fail to prevent persistent infection in this model. Here, we show that RHV-specific CD8 T cells, while induced early at high magnitude, do not develop into functional effectors capable of controlling virus. This defect was partially alleviated by short-term treatment with an HCV antiviral. Thus, like HCV, RHV triggers dysfunction of virus-specific CD8 T cells that are vital for infection resolution. Additional study of this evasion strategy and how to mitigate it could enhance our understanding of hepatotropic viral infections and lead to improved vaccines and therapeutics.

Hepatitis C virus (HCV) is an important and underreported infectious disease, causing chronic infection in ~71 million people worldwide. The limited host range of HCV, which robustly infects only humans and chimpanzees, has made studying this virus in vivo challenging and hampered the development of a desperately needed vaccine. The restrictions and ethical concerns surrounding biomedical research in chimpanzees has made the search for an animal model all the more important. In this review, we discuss different approaches that are being pursued toward creating small animal models for HCV infection. Although efforts to use a nonhuman primate species besides chimpanzees have proven challenging, important advances have been achieved in a variety of humanized mouse models. However, such models still fall short of the overarching goal to have an immunocompetent, inheritably susceptible in vivo platform in which the immunopathology of HCV could be studied and putative vaccines development. Alternatives to overcome this include virus adaptation, such as murine-tropic HCV strains, or the use of related hepaciviruses, of which many have been recently identified. Of the latter, the rodent/rat hepacivirus from Rattus norvegicus species-1 (RHV-rn1) holds promise as a surrogate virus in fully immunocompetent rats that can inform our understanding of the interaction between the immune response and viral outcomes (i.e., clearance vs. persistence). However, further characterization of these animal models is necessary before their use for gaining new insights into the immunopathogenesis of HCV and for conceptualizing HCV vaccines.

The infection is being eliminated as a public health threat by countries that introduce widespread testing and treatment for those at risk

Several drugs approved for the treatment of hepatitis C viral infection have been identified as potential candidates against COVID-19 caused by the SARS-CoV-2 coronavirus, according to a study based on extensive calculations using supercomputer simulations.

Researchers from Johannes Gutenberg University Mainz (JGU) in Germany simulated the way that about 42,000 different substances listed in open databases bind to certain proteins of SARS-CoV-2, and thereby inhibit the penetration of the virus into the human body or its multiplication. Using the powerful MOGON II supercomputer operated by JGU and the Helmholtz Institute Mainz, the researchers made more than 30 billion single calculations within two months.

They found that compounds from the four hepatitis C drugs simeprevir, paritaprevir, grazoprevir, and velpatasvir have a high affinity to bind SARS-CoV-2 very strongly and may therefore be able to prevent infection. "This computer simulation method is known as molecular docking and it has been recognised and used for years. It is much faster and less expensive than lab experiments," said Professor Thomas Efferth from JGU, lead author of the study published in the Bulletin of the World Health Organization. "As far as we know, we were the first to have used molecular docking with SARS-CoV-2. And it is fantastic news that we have found a number of approved hepatitis C drugs as promising candidates for treatment," Efferth said.

The results are also supported by the fact that both SARS-CoV-2 and the hepatitis C virus are a virus of the same type, a so-called single-stranded RNA virus, explained Efferth. According to the researchers, a natural substance from the Japanese honeysuckle (Lonicera japonica), which has been used in Asia against various other diseases for some time now, might be another strong candidate against SARS-CoV-2. "Our research results now need to be checked in laboratory experiments and clinical studies," said Efferth. Molecular docking had already been used successfully in the search for active substances against the coronaviruses MERS-CoV and SARS-CoV, he added.

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Doctors can safely transplant hepatitis C-infected hearts and lungs into people who are in dire need for a new organ, reports a new study. The findings

Survival rate of patients who received a heart transplant from a donor with hepatitis C to those who received hearts from donors without the disease was similar.

Hepatitis C screening and improved access to new treatments reduced the emergence of novel hepatitis C cases among HIV positive men, say researchers at

Only around five percent of the babies born to mothers with hepatitis C are themselves infected by the disease. A possible reason for this low figure

Patent holder and pharma major Gilead, announced voluntary licences with seven generic drug manufacturers in India to s

Berlin, May 5: Several drugs approved for the treatment of hepatitis C viral infection have been identified as potential candidates against COVID-19 caused by the SARS-CoV-2 coronavirus, according to a study based on extensive calculations using supercomputer simulations.

Interview with Anthony S. Fauci, MD, author of Sofosbuvir and Ribavirin for Hepatitis C Genotype 1 in Patients With Unfavorable Treatment Characteristics: A Randomized Clinical Trial

Interview with Mark S. Sulkowski, MD, author of Sofosbuvir and Ribavirin for Hepatitis C in Patients With HIV Coinfection

Interview with Michael J. Barry, MD, Task Force member and coauthor of Screening for Hepatitis C Virus Infection in Adolescents and Adults: US Preventive Services Task Force Recommendation Statement