A5012003601- SARS-CoV-2 and COVID-19 Research
- SARS-CoV-2 detection and testing
- Animal Virus Infections Studies
- COVID-19 Clinical Research Studies
- Hepatitis C virus research
- Viral Infections and Immunology Research
- Computational Drug Discovery Methods
- Cancer-related molecular mechanisms research
- Malaria Research and Control
- Calcium signaling and nucleotide metabolism
- Autophagy in Disease and Therapy
- Pharmacological Receptor Mechanisms and Effects
- Virus-based gene therapy research
- Phagocytosis and Immune Regulation
- RNA modifications and cancer
- Viral gastroenteritis research and epidemiology
- CRISPR and Genetic Engineering
- Viral Infections and Outbreaks Research
Hvidovre Hospital
2020-2024
Copenhagen University Hospital
2021-2024
University of Copenhagen
2020-2024
Hepatitis B Foundation
2024
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...
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...
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...
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.
We report the in vitro efficacy of ion-channel inhibitors amantadine, memantine and rimantadine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In VeroE6 cells, was most potent followed by amantadine (50% effective concentrations: 36, 80 116 µM, respectively). Rimantadine also showed highest selectivity index, (17.3, 12.2 7.6, Similar results were observed human hepatoma Huh7.5 lung carcinoma A549-hACE2 cells. Inhibitors interacted a similar antagonistic manner with...
Vaccines have relieved the public health burden of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and globally inactivated vaccines are most widely used. However, poor vaccination accessibility waning immunity maintain pandemic, driving emergence variants. We developed an SARS-CoV-2 (I-SARS-CoV-2) vaccine based on a viral isolate with Spike mutation D614G, produced in Vero cells scalable bioreactor, β-propiolactone, purified by membrane-based steric exclusion chromatography,...
Abstract In search for broad-spectrum antivirals, we discovered a small molecule inhibitor, RMC-113, that potently suppresses the replication of multiple RNA viruses including SARS-CoV-2 in human lung organoids. We demonstrated selective dual inhibition lipid kinases PIP4K2C and PIKfyve by RMC-113 target engagement its clickable analog. Advanced lipidomics revealed alteration SARS-CoV-2-induced phosphoinositide signature linked antiviral effect with functional inhibition. PIP4K2C’s roles...
Rapidly waning immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires continued global access to affordable vaccines. Globally, inactivated SARS-CoV-2 vaccines have been widely used during the pandemic. In this proof-of-concept study we adapted an original-D614G virus Vero cell culture as a strategy enhance vaccine manufacturing productivity. A passage 60 (P60) showed enhanced fitness and 50-fold increased yield in bioreactor compared virus. It further...
Abstract Antivirals targeting SARS-CoV-2 could improve treatment of COVID-19. We evaluated the efficacy clinically relevant hepatitis C virus (HCV) NS3 protease inhibitors (PI) against and their interactions with remdesivir, only antiviral approved for HCV PI showed differential potency in VeroE6 cell-based assays based on detection Spike protein. Linear boceprevir, telaprevir narlaprevir had 50% effective concentrations (EC50) ~40 μM. Among macrocyclic simeprevir, paritaprevir, grazoprevir,...
<title>Abstract</title> There is an ongoing need to expand the anti-SARS-CoV-2 armamentarium include agents capable of suppressing replication drug-resistant mutants emerging during monotherapy with approved direct-acting antivirals. Using a subgenomic SARS-CoV-2 replicon system, we studied RNA capacity nirmatrelvir (NTV)-resistant and their susceptibility next-generation Mpro inhibitors, including ibuzatrelvir (ITV), ensitrelvir (ETV), ML2006a4. Our findings revealed that E166V reduced...