A5048050876- Hepatitis B Virus Studies
- Hepatitis C virus research
- interferon and immune responses
- Viral gastroenteritis research and epidemiology
- Hepatitis Viruses Studies and Epidemiology
- Viral Infections and Vectors
- Viral Infections and Outbreaks Research
- SARS-CoV-2 and COVID-19 Research
- RNA Interference and Gene Delivery
- HIV Research and Treatment
- Liver Disease Diagnosis and Treatment
- Mosquito-borne diseases and control
- Animal Virus Infections Studies
- Viral Infections and Immunology Research
Baruch S. Blumberg Institute
2016
Hepatitis B Foundation
2016
Drexel University
2013-2014
IFNs are a family of cytokines that essential for the antiviral response in vertebrates. Not surprisingly, viruses have adapted to encode virulence factors cope with IFN response. Intriguingly, we show here all three types interferons, IFN-α, IFN-γ, and IFN-λ, efficiently promote infection by human coronavirus, HCoV-OC43, one major etiological agents common cold, through induction IFN-inducible transmembrane (IFITM) proteins. IFITMs typically exert their function inhibiting entry broad...
ABSTRACT Chronic hepatitis B virus (HBV) infection, a serious public health problem leading to cirrhosis and hepatocellular carcinoma, is currently treated with either pegylated alpha interferon (pegIFN-α) or one of the five nucleos(t)ide analogue viral DNA polymerase inhibitors. However, neither pegIFN-α nor analogues are capable reliably curing infection. In order develop novel antiviral drugs against HBV, we established cell-based screening assay by using an immortalized mouse...
Covalently closed circular DNA (cccDNA) of hepadnaviruses exists as an episomal minichromosome in the nucleus infected hepatocyte and serves transcriptional template for viral mRNA synthesis. Elimination cccDNA is prerequisite either a therapeutic cure or immunological resolution HBV infection. Although accumulating evidence suggests that inflammatory cytokines-mediated virally hepatocytes does occur plays essential role acute infection, molecular mechanism by which cytokines eliminate...
Chronicity of hepatitis B virus (HBV) infection is due to the failure a host mount sufficient immune response clear virus. The aim this study was identify small-molecular agonists pattern recognition receptor (PRR)-mediated innate control HBV infection. To achieve goal, coupled mouse macrophage and hepatocyte culture system mimicking intrahepatic environment established used screen compounds that activate macrophages produce cytokines, which in turn suppress replication hepatocyte-derived...
HBV RNA destabilizers are a class of small-molecule compounds that target the noncanonical poly(A) polymerases PAPD5 and PAPD7, resulting in degradation suppression viral proteins including hepatitis B surface antigen (HBsAg). AB-161 is next-generation destabilizer with potent antiviral activity, inhibiting HBsAg expressed from cccDNA integrated DNA cell-based models. exhibits broad genotype coverage, maintains activity against variants resistant to nucleoside analogs, shows additive effects...
Approved therapies for hepatitis B virus (HBV) treatment include nucleos(t)ides and interferon alpha (IFN-α) which effectively suppress viral replication, but they rarely lead to cure. Expression of proteins, especially surface antigen the (HBsAg) from covalently closed circular DNA (cccDNA) integrated genome, is believed contribute persistence HBV. This work focuses on that target expression HBV in particular HBsAg, differs current treatments. Here we describe identification AB-452, a...
The recent COVID-19 pandemic underscored the limitations of currently available direct-acting antiviral treatments against acute respiratory RNA-viral infections and stimulated major research initiatives targeting anticoronavirus agents. Two novel nsp5 protease (MPro) inhibitors have been approved, nirmatrelvir ensitrelvir, along with two existing nucleos(t)ide analogues repurposed as nsp12 polymerase inhibitors, remdesivir molnupiravir, but a need still exists for therapies improved potency...
Hepatitis B virus (HBV) mRNA metabolism is dependent upon host proteins PAPD5 and PAPD7 (PAPD5/7). PAPD5/7 are cellular, noncanonical, poly(A) polymerases (PAPs) whose main function to oligoadenylate the 3' end of noncoding RNA (ncRNA) for exosome degradation. HBV seems exploit these two ncRNA quality-control factors viral stabilization, rather than RG7834 a small-molecule compound that binds inhibits gene production in both tissue culture animal study. We reported was able destabilize...
Noncanonical poly(A) polymerases PAPD5 and PAPD7 (PAPD5/7) stabilize hepatitis B virus (HBV) RNA via the interaction with viral posttranscriptional regulatory element (PRE), representing new antiviral targets to control HBV metabolism, surface antigen (HBsAg) production, replication. Inhibitors targeting these proteins are being developed as therapies; therefore, it is important understand how PAPD5/7 coordinate RNA. Here, we utilized a potent small-molecule AB-452 chemical probe, along...
Lowering hepatitis B surface antigen (HBsAg) levels from covalently closed circular DNA (cccDNA) and the integrated genome could reduce persistence of virus (HBV) infection. Since HBV replication occurs in liver to ameliorate peripheral neuropathy observed with a first-generation tricyclic 4-pyridone PAPD5/7 inhibitor (
Abstract Noncanonical poly(A) polymerases PAPD5 and PAPD7 (PAPD5/7) stabilize HBV RNA via the interaction with viral post-transcriptional regulatory element (PRE), representing new antiviral targets to control metabolism, HBsAg production replication. Inhibitors targeting these proteins are being developed as therapies, therefore it is important understand how PAPD5/7 coordinate RNA. Here, we utilized a potent small-molecule AB-452 chemical probe, along genetic analyses dissect individual...