Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:6.2.1.1 (ACS)
 78,556 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nucleic acid polymers (NAPs) are broad spectrum antiviral agents whose antiviral activity in hepatitis B virus (HBV) infection is derived from their ability to block the release of the hepatitis B virus surface antigen (HBsAg). This pharmacological activity blocks replenishment of HBsAg in the circulation, allowing host mediated clearance. This effect has important clinical significance as the clearance of circulating HBsAg dramatically potentiates the ability of immunotherapies to restore functional control of HBV infection which persists after antiviral therapy is removed. These effects are reproducible in preclinical evaluations and in several clinical trials that have evaluated the activity of the lead NAP, REP 2139, in monotherapy and in combination with immunotherapy in hepatitis B e antigen (HBeAg) negative and HBeAg positive HBV infection and also in HBeAg negative HBV/hepatitis D virus (HDV) coinfection. These antiviral effects of REP 2139 are achieved in the absence of any direct immunostimulatory effect in the liver and also without any discernible direct interaction with viral components. The search for the host protein interaction with NAPs that drives their antiviral effects is ongoing, and the interaction targeted by REP 2139 within infected cells has not yet been elucidated. This article provides an updated review of available data on the effects of REP 2139 in HBV and HDV infection and the ability of REP 2139-based combination therapy to achieve functional control of HBV and HDV infection in patients.
ACS Infect Dis 2019 05 10
PMID:REP 2139: Antiviral Mechanisms and Applications in Achieving Functional Control of HBV and HDV Infection. 3019 30

Hepatitis delta virus (HDV) infects 10-20 million individuals worldwide and causes severe fulminant hepatitis with high likelihood of cirrhosis and hepatocellular carcinoma. HDV infection cannot occur in the absence of the surface antigen (HBsAg) of the hepatitis B virus. RNA interference is an effective mechanism by which to inhibit viral transcripts, and siRNA therapeutics sharing this mechanism have begun to demonstrate clinical efficacy. Here we assessed the outcome of HBV-targeting siRNA intervention against HDV and compared it to a direct anti-HDV siRNA approach in dually infected humanized mice. Treatment with ARB-1740, a clinical stage HBV-targeting siRNA agent delivered using lipid nanoparticle (LNP) technology, effectively reduced HBV viremia by 2.3 log10 and serum HBsAg by 2.6 log10, leading to 1.6 log10 reduction of HDV viremia. In contrast, HDV-targeting siRNA inhibited HDV in both blood and liver compartments without affecting HBV and PEGylated interferon-alpha reduced HBV viremia by 2.0 log10 but had no effect on HDV viremia under these study conditions. These results illustrate the inhibitory effects of siRNAs against these two viral infections and suggest that ARB-1740 may be of therapeutic benefit for hepatitis delta patients, a subpopulation with high unmet medical need.
ACS Infect Dis 2019 05 10
PMID:Hepatitis B Virus Therapeutic Agent ARB-1740 Has Inhibitory Effect on Hepatitis Delta Virus in a New Dually-Infected Humanized Mouse Model. 3040 57