- Hepatitis C virus research
- Hepatitis B Virus Studies
- SARS-CoV-2 and COVID-19 Research
- Liver Disease Diagnosis and Treatment
- HIV/AIDS drug development and treatment
- Monoclonal and Polyclonal Antibodies Research
- COVID-19 Clinical Research Studies
- SARS-CoV-2 detection and testing
- Viral gastroenteritis research and epidemiology
- Animal Virus Infections Studies
- Computational Drug Discovery Methods
- Respiratory viral infections research
- Viral Infections and Immunology Research
- Viral Infections and Outbreaks Research
- Malaria Research and Control
- interferon and immune responses
- Systemic Lupus Erythematosus Research
- Liver Disease and Transplantation
- Bacteriophages and microbial interactions
- MicroRNA in disease regulation
- Plant Virus Research Studies
- Cytomegalovirus and herpesvirus research
- Mast cells and histamine
- Long-Term Effects of COVID-19
- Chronic Lymphocytic Leukemia Research
University of Copenhagen
2016-2025
Copenhagen University Hospital
2014-2025
Hvidovre Hospital
2013-2023
Hepatitis B Foundation
2023
Consorci Institut D'Investigacions Biomediques August Pi I Sunyer
2007-2015
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas
2008-2015
Hospital Clínic de Barcelona
2011-2015
Universitat de Barcelona
2008-2011
The oral protease inhibitor nirmatrelvir is of key importance for prevention severe coronavirus disease 2019 (COVID-19). To facilitate resistance monitoring, we studied acute respiratory syndrome 2 (SARS-CoV-2) escape from in cell culture. Resistant variants harbored combinations substitutions the SARS-CoV-2 main (Mpro). Reverse genetics revealed that E166V and L50F + conferred high infectious culture, replicon, Mpro systems. While L50F, E166V, decreased replication activity, had fitness...
Chronic infection with hepatitis C virus (HCV) is an important cause of end stage liver disease worldwide. In the United States, most HCV-related associated genotype 1 infection, which remains difficult to treat. Drug and vaccine development was hampered by inability culture patient isolates representing HCV genotypes 1–7 subtypes; only a recombinant 2a genome (strain JFH1) spontaneously replicated in vitro. Recently, we identified three mutations F1464L/A1672S/D2979G (LSG) nonstructural...
Abstract Effective and affordable treatments for patients suffering from coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome 2 (SARS-CoV-2), are needed. We report in vitro efficacy of Artemisia annua extracts as well artemisinin, artesunate, artemether against SARS-CoV-2. The latter two approved active pharmaceutical ingredients anti-malarial drugs. Concentration–response antiviral treatment assays, based on immunostaining SARS-CoV-2 spike glycoprotein, revealed...
Efforts to mitigate the coronavirus disease 2019 (COVID-19) pandemic include screening of existing antiviral molecules that could be repurposed treat severe acute respiratory syndrome 2 (SARS-CoV-2) infections. Although SARS-CoV-2 replicates and propagates efficiently in African green monkey kidney (Vero) cells, antivirals such as nucleos(t)ide analogs (nuc’s) often show decreased activity these cells due inefficient metabolization.
Abstract The oral protease inhibitor nirmatrelvir is expected to play a pivotal role for prevention of severe cases coronavirus disease 2019 (COVID-19). To facilitate monitoring potentially emerging resistance, we studied acute respiratory syndrome 2 (SARS-CoV-2) escape from nirmatrelvir. Resistant variants selected in cell culture harbored different combinations substitutions the SARS-CoV-2 main (Mpro). Reverse genetic studies homologous infectious system revealed up 80-fold resistance...
Capsid virus-like particles (cVLP) have proven safe and immunogenic can be a versatile platform to counter pandemics. We aimed clinically test modular cVLP COVID-19 vaccine in individuals who were naive SARS-CoV-2.In this phase 1, single-centre, dose-escalation, adjuvant-selection, open-label clinical trial, we recruited participants at the Radboud University Medical Center Nijmegen, Netherlands, sequentially assigned them seven groups. Eligible healthy, aged 18-55 years, tested negative for...
Hepatitis C virus (HCV) infection is a leading cause of chronic liver diseases worldwide, but treatment options are limited. Basic HCV research required for vaccine and drug development has been hampered by inability to culture patient isolates, date only the JFH1 (genotype 2a) recombinant replicates spontaneously in hepatoma cells releases infectious virus. A chimera with 5′ end through NS2 from another genotype 2a strain, J6, had enhanced infectivity. However, full-length J6 clone (J6CF),...
As severe acute respiratory coronavirus 2 (SARS-CoV-2) variants continue to emerge, it is important characterize immune responses against which can inform on protection efficacies following booster vaccination. In this study, neutralizing breadth and antigen-specific CD8 + T cell were analyzed in both infection-naïve infection-experienced individuals administration of a bivalent Wuhan-Hu-1+BA.4/5 Comirnaty ® mRNA vaccine. Significantly higher titers found after vaccination compared the...
Hepatitis C virus (HCV) is a genetically diverse with multiple genotypes exhibiting remarkable differences, particularly in drug susceptibility. Drug and vaccine development will benefit from high-titer HCV cultures mimicking the complete viral life cycle, but such systems only exist for 1a 2a. We developed efficient culture epidemiologically important genotype 2b. Full-length molecular clones of patient strains DH8 DH10 were adapted to growth Huh7.5 cells by using F1468L/A1676S/D3001G (LSG)...
Antivirals targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could improve treatment of COVID-19. We evaluated the efficacy clinically relevant hepatitis C virus (HCV) NS3 protease inhibitors (PIs) against SARS-CoV-2 and their interactions with remdesivir, only direct-acting antiviral approved for COVID-19 treatment.
The COVID-19 pandemic continues to threaten healthcare systems worldwide due the limited access vaccines, suboptimal treatment options, and continuous emergence of new more transmissible SARS-CoV-2 variants. Reverse-genetics studies viral genes mutations have proven highly valuable in advancing basic virus research, leading development therapeutics. We developed a functional versatile full-length infectious system by cloning sequence associated isolate (DK-AHH1) into bacterial artificial...
Licensed vaccines against SARS-CoV-2 effectively protect severe disease, but display incomplete protection virus transmission. Mucosal providing immune responses in the upper airways are one strategy to
Hypervariable region 1 (HVR1) of envelope protein 2 (E2) hepatitis C virus (HCV) serves important yet undefined roles in the viral life cycle. We previously showed that viability HVR1-deleted JFH1-based recombinants with Core-NS2 H77 (H77(ΔHVR1), genotype 1a) and S52 (S52(ΔHVR1), 3a) Huh7.5 cells was rescued by E2 substitutions N476D/S733F an E1 substitution, A369V, respectively; J6 (J6(ΔHVR1), 2a) fully viable. In single-cycle production assays, where HCV RNA transfected into...
The first discovered and sequenced hepatitis C virus (HCV) genome the in vivo infectious HCV clones originated from prototype strains HCV-1 H77, respectively, both widely used research of this important human pathogen. In present study, we developed efficient cell culture systems for these genotype 1a by using HCV-1/SF9_A H77C clones. We initially adapted a with 5'UTR-NS5A (where UTR stands untranslated region) JFH1 NS5B-3'UTR (5-5A recombinant), including 2a-derived mutations...
ABSTRACT Various protease inhibitors (PIs) currently are becoming available for treatment of hepatitis C virus (HCV). For genotype 1, substitutions at NS3 positions 155, 156, and 168 the main determinants PI resistance. other genotypes, similar were selected during but not characterized systematically. To elucidate impact key resistance on genotypes 2 to 6, we engineered R155A/E/G/H/K/Q/T, A156G/S/T/V, D/Q168A/E/G/H/N/V into HCV recombinants expressing 6 proteases. We evaluated viral fitness...