A5061179606- Hepatitis B Virus Studies
- Hepatitis C virus research
- HIV/AIDS drug development and treatment
- Viral gastroenteritis research and epidemiology
- Herpesvirus Infections and Treatments
- Liver Disease Diagnosis and Treatment
- Viral Infections and Outbreaks Research
- HIV Research and Treatment
- Bacteriophages and microbial interactions
- Hepatitis Viruses Studies and Epidemiology
- Monoclonal and Polyclonal Antibodies Research
- Synthesis of Organic Compounds
- Animal Virus Infections Studies
- Polyomavirus and related diseases
- RNA and protein synthesis mechanisms
- Full-Duplex Wireless Communications
- Toxin Mechanisms and Immunotoxins
- Parvovirus B19 Infection Studies
- Viral Infections and Vectors
- Poxvirus research and outbreaks
- SARS-CoV-2 and COVID-19 Research
- Viral-associated cancers and disorders
- Computational Drug Discovery Methods
- Mosquito-borne diseases and control
- Viral Infections and Immunology Research
Saint Louis University
2016-2025
UCLouvain Saint-Louis Brussels
2005-2024
Baylor College of Medicine
2017
Baruch S. Blumberg Institute
2017
Hepatitis B Foundation
2017
Saint Louis University
2008
Center of Molecular Immunology (Cuba)
2008
Howard Hughes Medical Institute
1993-1996
University of Göttingen
1996
University of California, San Francisco
1993-1995
The efficiency of hepatitis C virus (HCV) transmission by sexual activity remains controversial. We conducted a cross-sectional study HCV-positive subjects and their partners to estimate the risk for HCV infection among monogamous heterosexual couples. A total 500 anti-HCV-positive, human immunodeficiency virus-negative index long-term were studied. Couples interviewed separately lifetime factors infection, within-couple practices, sharing personal grooming items. Blood samples tested...
Silymarin, an extract from milk thistle (Silybum marianum), and its purified flavonolignans have been recently shown to inhibit hepatitis C virus (HCV) infection, both in vitro vivo. In the current study, we further characterized silymarin's antiviral actions. Silymarin had effects against cell culture (HCVcc) infection that included inhibition of entry, RNA protein expression, infectious production. did not block HCVcc binding cells but inhibited entry several viral pseudoparticles (pp),...
Acute infection with hepatitis C virus (HCV) rarely is identified, and hence, the determinants of spontaneous resolution versus chronicity remain incompletely understood. In particular, because retrospective nature unknown source in most human studies, direct evidence for emergence escape mutations immunodominant major histocompatibility complex class I–restricted epitopes leading to immune evasion extremely limited. two patients infected accidentally an identical HCV strain but who...
Nucleos(t)ide analog therapy blocks DNA synthesis by the hepatitis B virus (HBV) reverse transcriptase and can control infection, but treatment is life-long has high costs unpredictable long-term side effects. The profound suppression of HBV nucleos(t)ide analogs their ability to cure some patients indicates that they push brink extinction. Consequently, more could be cured suppressing replication further using a new drug in combination with analogs. ribonuclease H (RNAseH) logical target...
The continuous spread of SARS-CoV-2 calls for more direct-acting antiviral agents to combat the highly infectious variants. main protease (Mpro) is an promising target anti-SARS-CoV-2 drug design. Here, we report discovery potent non-covalent non-peptide Mpro inhibitors featuring a 1,2,4-trisubstituted piperazine scaffold. We systematically modified hit MCULE-5948770040 by structure-based rational design combined with multi-site binding and privileged structure assembly strategies. optimized...
Assembly of the enveloped hepatitis B virus (HBV) is initiated by packaging RNA pregenome and viral reverse transcriptase-DNA polymerase into a nucleocapsid. The then transcribed single-stranded minus-polarity DNA, which subsequently replicated to double-stranded DNA. All replicative intermediates are observable in capsids within infected liver, but only relatively mature nucleocapsids containing partially double stranded DNA found secreted virions. This observation suggests that maturation...
Replication of the hepadnavirus genome occurs by reverse transcription an RNA pregenome and is mediated viral polymerase; polymerase also required for packaging through interaction with signal, epsilon. Previous work suggested that minus-strand DNA initiates within sequence element DR1 (direct repeat 1) disruption activates a cryptic initiation site in downstream copy However, using active duck hepatitis B virus expressed yeast Ty vector system, we demonstrate synthesis DNAs 5' ends at...
ABSTRACT Treating chronic hepatitis C virus (HCV) infection using pegylated alpha interferon and ribavirin leads to sustained clearance of clinical improvement in approximately 50% patients. Response rates are lower among patients with genotype 1 than genotypes 2 3 African-American (AA) compared Caucasian (CA) Using DNA microarrays, gene expression was assessed for a group 33 36 American HCV during the first 28 days treatment. Results were examined respect treatment responses race. Patients...
There is an association between expression of the MHC class I molecule HLA-B27 and protection following human infection with either HIV or HCV. In both cases, has been linked to presentation a single immunodominant viral peptide epitope CD8+ T cells. If mutates HLA-B27–binding anchor this escape protective immune response, result less-fit virus that requires additional compensatory clustered mutations. Here, we sought determine whether HLA-B27–restricted HCV was similarly constrained by...
ABSTRACT Pegylated alpha interferon and ribavirin therapy for hepatitis C virus (HCV) genotype 1 infection fails half of Caucasian American patients (CA) more often African Americans (AA). The reasons these low response rates are unknown. HCV is highly genetically variable, but it unknown how this variability affects to therapy. To assess effects viral diversity on therapy, the complete pretreatment open reading frame was sequenced using samples from 94 participants in Virahep-C study....
ABSTRACT Hepatitis B virus (HBV) remains a major human pathogen despite the development of both antiviral drugs and vaccine, in part because current therapies do not suppress HBV replication far enough to eradicate virus. Here, we screened 51 troponoid compounds for their ability RNaseH activity based on activities α-hydroxytropolones against HIV RNaseH, with goal determining whether tropolone pharmacophore may be promising scaffold anti-HBV drug development. Thirteen inhibited best 50%...
Potential conflict of interest: Dr. Block owns stock, holds intellectual property rights, and received grants from Arbutus. He is employed by stock in Contravir. director has equity Glycotest. Chisari consults for Gilead. H. Guo Assembly. Alios. J. Lok Bristol‐Myers Squibb Kowdley consults, advises, on the speakers' bureau Glenn by, Riboscience. Eiger. Feld AbbVie, Gilead, Janssen, Merck. Abbott. Hu Gilead Roche. Sanofi El‐Serag Wako, Mason Revill Chang advises Arbutus Alnylam. Locarnini...
Hepatitis C virus (HCV) is a common RNA that causes hepatitis and liver cancer. Infection treated with IFN-α ribavirin, but this expensive physically demanding therapy fails in half of patients. The genomic sequences independent HCV isolates differ by approximately 10%, the effects variation on response to are unknown. To address question, we analyzed amino acid covariance within full viral coding region pretherapy from 94 participants Viral Resistance Antiviral Therapy Chronic (Virahep-C)...
Silymarin prevents liver disease in many experimental rodent models, and is the most popular botanical medicine consumed by patients with hepatitis C. Silibinin a major component of silymarin, consisting flavonolignans silybin A B, which are insoluble aqueous solution. chemically modified soluble version silibinin, SIL, has been shown to potently reduce C virus (HCV) RNA levels vivo when administered intravenously. silibinin inhibit HCV infection cell culture targeting multiple steps...
The spread of SARS-CoV-2 keeps threatening human life and health, small-molecule antivirals are in demand. main protease (Mpro) is an effective highly conserved target for anti-SARS-CoV-2 drug design. Herein, we report the discovery potent covalent non-peptide-derived Mpro inhibitors. A series compounds with a piperazine scaffold containing different warheads were designed synthesized. Among them, GD-9 was identified as most compound significant enzymatic inhibition (IC50 = 0.18 μM) good...
Hepatitis B virus (HBV) ribonuclease H (RNaseH) inhibitors are a potent class of antivirals that prevent degradation the viral pregenomic RNA during reverse transcription and block formation mature HBV DNAs. Development RNaseH is entering advanced preclinical analyses. To ensure mechanism action was fully understood, we defined effects on other steps replication. Some N -hydroxypyridinedione (HPD) significantly reduced accumulation capsids in HBV-replicating cells. A representative HPD 1466...
While the intracellular pool of encapsidated hepatitis B viral DNA contains genomes in all stages replication, serum-derived virions contain predominantly mature, partially duplex, circular genomes. To account for this finding, Summers and Mason proposed 1982 that virion envelopment is somehow linked to state genomic maturation (J. W.S. Mason, Cell 29:403-415, 1982). Core gene mutations with phenotypes consistent concept have previously been identified duck virus (DHBV). Here we show DHBV...