scholarly journals Recent Advances in Hepatitis B Treatment

2021 ◽  
Vol 14 (5) ◽  
pp. 417
Author(s):  
Georgia-Myrto Prifti ◽  
Dimitrios Moianos ◽  
Erofili Giannakopoulou ◽  
Vasiliki Pardali ◽  
John E. Tavis ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Viral Entry ◽  
Antiviral Agents ◽  
Pegylated Interferon ◽  
Effective Vaccine ◽  
Immune Modulators ◽  
Treatment Regimens ◽  
Entry Inhibitors ◽  
Hepatitis B Treatment ◽  
Key Steps

Hepatitis B virus infection affects over 250 million chronic carriers, causing more than 800,000 deaths annually, although a safe and effective vaccine is available. Currently used antiviral agents, pegylated interferon and nucleos(t)ide analogues, have major drawbacks and fail to completely eradicate the virus from infected cells. Thus, achieving a “functional cure” of the infection remains a real challenge. Recent findings concerning the viral replication cycle have led to development of novel therapeutic approaches including viral entry inhibitors, epigenetic control of cccDNA, immune modulators, RNA interference techniques, ribonuclease H inhibitors, and capsid assembly modulators. Promising preclinical results have been obtained, and the leading molecules under development have entered clinical evaluation. This review summarizes the key steps of the HBV life cycle, examines the currently approved anti-HBV drugs, and analyzes novel HBV treatment regimens.

Inhibitory Effects of Amentoflavone and Orobol on Daclatasvir-Induced Resistance-Associated Variants of Hepatitis C Virus

2018 ◽  
Vol 46 (04) ◽  
pp. 835-852 ◽  
Author(s):  
Wei-Ping Lee ◽  
Keng-Li Lan ◽  
Shi-Xian Liao ◽  
Yi-Hsiang Huang ◽  
Ming-Chih Hou ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Viral Entry ◽  
Antiviral Agents ◽  
Cost Effective ◽  
Pegylated Interferon ◽  
Chinese Herbs ◽  
Inhibitory Effects ◽  
Direct Acting Antiviral ◽  
Direct Acting

Hepatitis C virus (HCV) is recognized as a major causative agent of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Despite rapid progress in the development of direct-acting antivirals (DAA) against HCV infection in recent years, cost-effective antiviral drugs with more affordable prices still need to be developed. In this study, we screened a library of natural compounds to identify natural HCV inhibitors. The library of the pure compounds extracted from Chinese herbs deposited in the chemical bank of National Research Institute of Chinese Medicine (NRICM), Taiwan was screened in the cell culture-derived HCV (HCVcc) system. We identified the flavone or flavan-based compounds amentoflavone, 7,4[Formula: see text]-dihydroxyflavanone, and orobol with the inhibition of viral entry, replication, and translation of the HCV life cycle. Amentoflavone and orobol also showed inhibitory effects on resistant-associated variants to the NS5A inhibitor daclatasvir. The results of this study have the potential to benefit patients who are intolerant to the adverse effect of pegylated interferon or who harbor resistant strains refractory to treatment by current direct-acting antiviral agents.

scholarly journals In Vitro Systems for Studying Different Genotypes/Sub-Genotypes of Hepatitis B Virus: Strengths and Limitations

Viruses ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 353 ◽  
Author(s):  
Constance N. Wose Kinge ◽  
Nimisha H. Bhoola ◽  
Anna Kramvis
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
In Vitro Model ◽  
Antiviral Agents ◽  
Model Systems ◽  
Effective Vaccine ◽  
B Virus ◽  
In Vitro Systems ◽  
Vitro Model

Hepatitis B virus (HBV) infects the liver resulting in end stage liver disease, cirrhosis, and hepatocellular carcinoma. Despite an effective vaccine, HBV poses a serious health problem globally, accounting for 257 million chronic carriers. Unique features of HBV, including its narrow virus–host range and its hepatocyte tropism, have led to major challenges in the development of suitable in vivo and in vitro model systems to recapitulate the HBV replication cycle and to test various antiviral strategies. Moreover, HBV is classified into at least nine genotypes and 35 sub-genotypes with distinct geographical distributions and prevalence, which have different natural histories of infection, clinical manifestation, and response to current antiviral agents. Here, we review various in vitro systems used to study the molecular biology of the different (sub)genotypes of HBV and their response to antiviral agents, and we discuss their strengths and limitations. Despite the advances made, no system is ideal for pan-genotypic HBV research or drug development and therefore further improvement is required. It is necessary to establish a centralized repository of HBV-related generated materials, which are readily accessible to HBV researchers, with international collaboration toward advancement and development of in vitro model systems for testing new HBV antivirals to ensure their pan-genotypic and/or customized activity.

Targeting Chikungunya Virus Entry: alternatives for new inhibitors in drug discovery

2021 ◽  
Vol 28 ◽  
Author(s):  
Leandro Rocha Silva ◽  
Érica Erlanny da Silva Rodrigues ◽  
Jamile Taniele-Silva ◽  
Letícia Anderson ◽  
João Xavier de Araújo-Júnior ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Viral Entry ◽  
Chikungunya Virus ◽  
Viral Disease ◽  
Virus Budding ◽  
Drug Candidates ◽  
Entry Inhibitors ◽  
Repurposed Drugs ◽  
Approved Drugs ◽  
Key Steps

: Chikungunya virus (CHIKV) is an Alphavirus (Togaviridae) responsible for Chikungunya fever (CHIKF) that is mainly characterized by a severe polyarthralgia, in which it is transmitted by the bite of infected Aedes aegypti and Ae. albopictus mosquitoes. Nowadays, there no licensed vaccines or approved drugs to specifically treat this viral disease. Structural viral proteins participate in key steps of its replication cycle, such as viral entry, membrane fusion, nucleocapsid assembly, and virus budding. In this context, envelope E3-E2-E1 glycoproteins complex could be targeted for designing new drug candidates. In this review, aspects of the CHIKV entry process are discussed to provide insights to assist the drug discovery process. Moreover, several natural, nature-based and synthetic compounds, as well as repurposed drugs and virtual screening, are also explored as alternatives for developing CHIKV entry inhibitors. Finally, we provided a complimentary analysis of studies involving inhibitors that were not explored by in silico methods. Based on this, Phe118, Val179, and Lys181 were found to be the most frequent residues, being present in 89.6, 82.7, and 93.1% of complexes, respectively. Lastly, some chemical aspects associated with interactions of these inhibitors and mature envelope E3-E2-E1 glycoproteins’ complex were discussed to provide data for scientists worldwide, supporting their search for new inhibitors against this emerging arbovirus.

scholarly journals Advances in hepatitis B therapeutics

2020 ◽  
Vol 7 ◽  
pp. 204993612096502
Author(s):  
Vicente Soriano ◽  
Pablo Barreiro ◽  
Edward Cachay ◽  
Shyamasundaran Kottilil ◽  
José V. Fernandez-Montero ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Significant Proportion ◽  
Clinical Development ◽  
Drug Discontinuation ◽  
Virus Eradication ◽  
Immune Modulators ◽  
Entry Inhibitors ◽  
Hbsag Loss ◽  
Treatment Benefits ◽  
Advanced Stages

Despite the availability of both effective preventive vaccines and oral antivirals, over 250 million people are chronically infected with the hepatitis B virus (HBV). Globally, chronic hepatitis B is the leading cause of hepatocellular carcinoma, which represents the third cause of cancer mortality, accounting for nearly 1 million annual deaths. Current oral nucleos(t)ide therapy with tenofovir or entecavir suppresses serum HBV-DNA in most treated patients, but rarely is accompanied by HBsAg loss. Thus, treatment has to be given lifelong to prevent viral rebound. A broad spectrum of antivirals that block the HBV life cycle at different steps are in clinical development, including entry inhibitors, cccDNA disrupters/silencers, translation inhibitors, capsid assembly modulators, polymerase inhibitors and secretion inhibitors. Some of them exhibit higher potency than current oral nucleos(t)ides. Drugs in more advanced stages of clinical development are bulevirtide, JNJ-6379, ABI-H0731, ARO-HBV and REP-2139. To date, only treatment with ARO-HBV and with REP-2139 have resulted in HBsAg loss in a significant proportion of patients. Combination therapies using distinct antivirals and/or immune modulators are expected to maximize treatment benefits. The current goal is to achieve a ‘functional cure’, with sustained serum HBsAg after drug discontinuation. Ultimately, the goal of HBV therapy will be virus eradication, an achievement that would require the elimination of the cccDNA reservoir within infected hepatocytes.

scholarly journals Treatment of Hepatitis B in Decompensated Liver Cirrhosis

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Richard Guan ◽  
Hock Foong Lui
Keyword(s):  
Chronic Hepatitis ◽  
Liver Disease ◽  
Hepatitis B ◽  
Antiviral Agents ◽  
Antiviral Agent ◽  
Decompensated Cirrhosis ◽  
Decompensated Liver Cirrhosis ◽  
Chronic Hepatitis B Infection ◽  
Advanced Cirrhosis ◽  
Hepatitis B Treatment

Chronic hepatitis B infection progresses from an asymptomatic persistently infected state to chronic hepatitis, cirrhosis, decompensated liver disease, and/or hepatocellular carcinoma. About 3% of patients with chronic hepatitis develop cirrhosis yearly, and about 5% of individuals with hepatitis B cirrhosis become decompensated annually. The outcome for patients with decompensated cirrhosis is bleak. Lamivudine, the first oral antiviral agent available for hepatitis B treatment is safe and effective and can improve or stabilize liver disease in patients with advanced cirrhosis and viraemia. Viral resistance restricts its prolonged use. Entecavir and tenofovir are newer agents with excellent resistance profile to date. These and some other antiviral agents are being investigated for optimal use in this rather challenging patient group.

The use of pseudotyped coronaviruses for the screening of entry inhibitors: Green tea extract inhibits the entry of SARS-CoV-1, MERS-CoV, and SARS-CoV-2 by blocking receptor-spike interaction

2021 ◽  
Vol 22 ◽  
Author(s):  
Jeswin Joseph ◽  
Thankamani Karthika ◽  
V.R. Akshay Das ◽  
V. Stalin Raj
Keyword(s):  
Green Tea ◽  
Viral Entry ◽  
Neutralizing Antibodies ◽  
High Titer ◽  
Antiviral Agents ◽  
Natural Compounds ◽  
Cell Surface Receptor ◽  
Soluble Form ◽  
Entry Inhibitors ◽  
Wide Range

Background: Coronaviruses (CoVs) infect a wide range of animals and birds. Their tropism is primarily determined by the ability of the spike protein to bind to a host cell surface receptor. The ongoing outbreak of SARS-CoV-2 inculcates the need for the development of effective intervention strategies. Objectives: In this study, we aim to produce pseudotyped coronaviruses of SARS-CoV-1, MERS-CoV, and SARS-CoV-2 and show its applications, including virus entry, neutralization, and screening of entry inhibitors from natural products. Methods: Here, we generated VSV-based pseudotyped coronaviruses (CoV-PVs) for SARS-CoV-1, MERS-CoV, and SARS-CoV-2. Recombinant spike proteins of SARS-CoV-1, MERS-CoV, and SARS-CoV-2 were transiently expressed in HEK293T cells followed by infection with recombinant VSV. High titer pseudoviruses were harvested and subjected to distinct validation assays, which confirms the proper spike pseudotyping. Further, specific receptor-mediated entry was confirmed by antibody neutralization and soluble form of receptor inhibition assay on Vero E6 cells. Next, these CoV-PVs were used for screening of antiviral activity of natural compounds such as green tea and Spirulina extract. Results: Medicinal plants and natural compounds have been traditionally used as antiviral agents. In the first series of experiments, we demonstrated that pseudotyped viruses specifically bind to their receptors for cellular entry. SARS-CoV-1 and MERS-CoV anti-sera neutralize SARS-CoV-1-PV and SARS-CoV-2-PV, and MERS-CoV-PV, respectively. Incubation of soluble ACE2 with CoV-PVs inhibited entry of SARS-CoV-1 and SARS-CoV-2 PVs but not MERS-CoV-PV. Also, transient expression of ACE2 and DPP4 in non-permissive BHK21 cells enabled infection by SARS-CoV-1-PV, SARS-CoV-2-PV, and MERS-CoV-PV, respectively. Next, we showed the antiviral properties of known entry inhibitors of enveloped viruses, Spirulina, and green tea extracts against CoV-PVs. SARS-CoV-1-PV, MERS-CoV-PV, and SARS-CoV-2-PV entry was blocked with higher efficiency when preincubated with either green tea or Spirulina extracts. Green tea provided a better inhibitory effect by binding to the S1 domain of the spike and blocking the spike interaction with its receptor. Conclusion: In summary, we demonstrated that pseudotyped viruses are an ideal tool for studying viral entry, quantification of neutralizing antibodies, and screening of entry inhibitors in a BSL-2 facility. Moreover, green tea might be a promising natural remedy against emerging coronaviruses.

scholarly journals Novel Therapies in HBV Infection

2019 ◽  
Vol 13 (1) ◽  
Author(s):  
Giuseppe Foti ◽  
Vincenzo Scaglione ◽  
Carlo Torti
Keyword(s):  
Hepatitis B ◽  
Viral Replication ◽  
Immune Modulation ◽  
Hepatitis B Surface Antigen ◽  
Small Interfering Rnas ◽  
Therapeutic Vaccines ◽  
Immune Modulators ◽  
Entry Inhibitors ◽  
Clinical Complications ◽  
Increased Risk

Current treatments for chronic hepatitis B are able to provide a sustained suppression of the viral replication (i.e., persistent undetectability of HBV DNA). This leads to improvement of liver fibrosis and reduction of clinical complications. However, hepatitis B surface antigen (HBsAg) persists in most patients, probably justifying a still increased risk of hepatocellular carcinoma. Indeed, obtaining a complete and sterilizing cure with elimination of the covalently closed circular DNA (cccDNA) or silencing its activity is still a holy grail. New molecules are under evaluation to suppress viral replication acting on multiple phases of the HBV cycle or improve specific immune response against HBV. Molecules acting on HBV cycle have already showed encouraging results, such as entry inhibitors, small interfering RNAs (siRNAs), capsid assembly modulators (CAMs), nucleic acid polymers (NAPs). Also, promising results have been observed with immune-modulators, therapeutic vaccines, and other immune-based approaches. Among these, toll-like (TLR) or anti-programmed receptor agonists antibody 1 of the cell death protein (PD1) (e.g., nivolumab) are most promising. This paper describes newer drugs appearing on the horizon, including antiviral drugs targeting different steps of the HBV life cycle and therapeutic approaches based on immune-modulation.

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