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Articles by Johan Neyts
Towards broader-spectrum direct-acting antivirals against RNA viruses
Abstract Small molecule antiviral drugs have transformed the management of infections such as those caused by HIV, hepatitis B virus, hepatitis C virus, herpesviruses and influenza viruses. Effective antiviral therapeutics remain unavailable for many other often life-threatening viral infections, many of which are caused by RNA viruses.
Oropouche virus causes severe congenital disease in embryonic mice
Abstract The recent outbreak of Oropouche virus (OROV) in Latin-America with unprecedented reports of vertical transmission resulting in congenital malformations and fetal death, redefines the threat posed by this arbovirus. We discover that injection of a low inoculum of the epidemic OROVIRCCS-SCDC_1/2024 strain into the placenta of Swiss mice results in viral replication across embryonic organs, in particular the brain.
Dual-fluorescence reporter-based assay for rapid quantitative evaluation of antiviral activity against Venezuelan equine encephalitis virus
Abstract Venezuelan equine encephalitis virus (VEEV) is a mosquito-borne alphavirus primarily infecting equines, causing severe illness or death. The virus can also infect humans causing severe neurological complications. There are no antivirals or human vaccines available. Although major outbreaks have been relatively rare in recent years, there is a need for antiviral drugs to combat this virus, both as a precaution against epidemics and for biological defense.
A robust cell-based infection model for Rhinovirus C research and antiviral drug discovery
Abstract Rhinoviruses (RV) comprise three species, RV-A, RV-B, and RV-C, with approximately 170 types. RV-C is associated with severe respiratory illness, particularly in children and individuals with asthma or chronic obstructive pulmonary disease, underscoring the need for effective antiviral strategies. Progress in RV-C research and drug discovery has been limited by the lack of robust, scalable cell-based infection models that recapitulate the complete RV-C replication cycle.
CD4 + T cell-mediated immunity protects from VSV-SUD lethal challenge in a mouse model of Sudan virus infection
Abstract Recurring outbreaks of filoviruses, including Ebola virus and Sudan virus, threaten to cause large epidemics. No treatment or vaccine is available for Sudan virus and how protective immunity is achieved remains unknown. To unravel mechanisms contributing to protection, we used a surrogate mouse model of Sudan virus infection amenable to deep functional analysis.
COVID-19-related inflammation of the placenta impedes fetal development in pregnant hamsters - Nature Communications
Abstract Pregnant women are at higher risk of severe COVID-19, with vaccine access and hesitancy remaining a challenge. Here, we use a pregnant female hamster model of COVID-19 to explore the effects of maternal infection on pregnancy, revealing a significant increase in intrauterine growth restriction (IUGR) due to placental inflammation. Viral infection causes bronchopneumonia and weight loss in infected dams, but no vertical transmission occurs.
Immunological and transcriptomic profile of chimeric live-attenuated Zika vaccine linked to protection in non-human primates - Nature Communications
Abstract Zika virus (ZIKV) is typically mild in humans but can cause severe congenital defects when contracted during pregnancy. Chimeric live-attenuated vaccine candidate YF-ZIK previously showed protective efficacy against lethal infection and developmental abnormalities in mice after a single dose. Here we demonstrate that YF-ZIK is safe, induces antiviral immunity, and protects rhesus macaques against high-dose experimental challenge.
Ultrapotent SARS coronavirus-neutralizing single-domain antibodies that clamp the spike at its base - Nature Communications
Abstract Therapeutic monoclonal antibodies can prevent severe disease in SARS-CoV-2 exposed individuals. However, currently circulating virus variants have evolved to gain significant resistance to nearly all neutralizing human immune system-derived therapeutic monoclonal antibodies that had previously been emergency-authorized for use in the clinic.
6-Chlorocoumarin Conjugates with Nucleobases and Nucleosides as Potent Anti-Hepatitis C Virus Agents
1. Introduction The hepatitis C virus (HCV) primarily influences the liver and is an infectious disease that is observed worldwide [1]. According to the World Health Organization, over 50 million individuals are chronically infected with HCV, and around 200,000 deaths each year are attributed to HCV-induced cirrhosis and liver cancer [2]. In the absence of a vaccine [3], treatment relies on direct-acting antiviral (DAA) agents [2].
A small-molecule SARS-CoV-2 inhibitor targeting the membrane protein - Nature
Abstract The membrane (M) protein of betacoronaviruses is well conserved and has a key role in viral assembly1,2. Here we describe the identification of JNJ-9676, a small-molecule inhibitor targeting the coronavirus M protein. JNJ-9676 demonstrates in vitro nanomolar antiviral activity against SARS-CoV-2, SARS-CoV and sarbecovirus strains from bat and pangolin zoonotic origin.
Pan-serotype dengue virus inhibitor JNJ-A07 targets NS4A-2K-NS4B interaction with NS2B/NS3 and blocks replication organelle formation - Nature Communications
Abstract Dengue fever represents a significant medical and socio-economic burden in (sub)tropical regions, yet antivirals for treatment or prophylaxis are lacking. JNJ-A07 was described as highly active against the different genotypes within each serotype of the disease-causing dengue virus (DENV). Based on clustering of resistance mutations it has been assumed to target DENV non-structural protein 4B (NS4B).
The triple combination of Remdesivir (GS-441524), Molnupiravir and Ribavirin is highly efficient in inhibiting coronavirus replication in human nasal airway epithelial cell cultures and in a hamster infection model
Abstract The use of fixed dose-combinations of antivirals with different mechanisms of action has proven a key in the successful treatment of infections with HIV and HCV. For the treatment of infections with SARS-CoV-2 and possible future epi-/pandemic coronaviruses, it will be important to explore the efficacy of combinations of different drugs, in particular to avoid resistance development, such as in patients with immunodeficiencies.
Hepatitis E virus replication is facilitated by epithelial cell turnover and targets enteroendocrine cells in human intestinal organoids
Abstract Hepatitis E virus (HEV) is an emerging pathogen responsible for acute viral hepatitis globally. There is no specific antiviral and non-universal vaccine, partly due to limitations in its in vitro cultivation. Although HEV is mainly fecal-oral transmitted and excreted in the feces in high titers, the role of the gut in HEV-induced disease remains unexplored. Little is known about how the virus spreads from gut to liver, or about the gut potentially acting as an HEV reservoir.
Multiplexed multicolor antiviral assay amenable for high-throughput research - Nature Communications
Abstract To curb viral epidemics and pandemics, antiviral drugs are needed with activity against entire genera or families of viruses. Here, we develop a cell-based multiplex antiviral assay for high-throughput screening against multiple viruses at once, as demonstrated by using three distantly related orthoflaviviruses: dengue, Japanese encephalitis and yellow fever virus.
Blocking NS3–NS4B interaction inhibits dengue virus in non-human primates - Nature
Compound The synthesis of JNJ-1802 (Fig. 1a) is published in patent application WO 2016/180696. The synthesis and chemical characterization of JNJ-1802 are also provided in the Supplementary Methods. For in vitro experiments, the compound was dissolved in 100% dimethyl sulfoxide (DMSO) as a 10 mg ml−1 or a 5 mM stock. For oral administration in AG129 mice, JNJ-1802 was dissolved in 80% polyethylene glycol 400 (PEG400)/20% H2O. For oral administration in rhesus macaques (M.
IJMS | Free Full-Text | Insertion of an Amphipathic Linker in a Tetrapodal Tryptophan Derivative Leads to a Novel and Highly Potent Entry Inhibitor of Enterovirus A71 Clinical Isolates
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Updated vaccine protects against SARS-CoV-2 variants including Omicron (B.1.1.529) and prevents transmission in hamsters - Nature Communications
Abstract Current COVID-19 vaccines are based on prototypic spike sequences from ancestral 2019 SARS-CoV-2 strains. However, the ongoing pandemic is fueled by variants of concern (VOC) escaping vaccine-mediated protection. Here we demonstrate how immunization in hamsters using prototypic spike expressed from yellow fever 17D (YF17D) as vector blocks ancestral virus (B lineage) and VOC Alpha (B.1.1.7) yet fails to fully protect from Beta (B.1.351).
Assessment of the anti-norovirus activity in cell culture using the mouse norovirus: Early mechanistic studies
Introduction We here describe the first steps towards the characterization of the molecular mechanism of action of a norovirus antiviral, as a follow-up to the identification of active molecules (in part 1 of this protocol).1 After running a set of assays that identify novel norovirus inhibitors, we propose an early characterization of these inhibitors by means of time of drug addition studies and tentative selection of drug-resistant variants.
Screening and in vitro antiviral assessment of small molecules against fluorescent protein-expressing Bunyamwera virus in a cell-based assay using high-content imaging - Sebastiaan ter Horst, Winston Chiu, Johan Neyts, Joana Rocha-Pereira, 2021
Abstract Many species of the order Bunyavirales contain potentially fatal viruses that lack effective medical countermeasures and are therefore collectively a major public health threat. Here, we describe a cell-based assay using Bunyamwera virus (BUNV)-mCherry to identify and characterize new antiviral molecules against bunyaviruses. BUNV is the type species for the genus Orthobunyavirus and has been reported to cause mild symptoms in humans, such as fever, joint pain, and rash.
Assessment of the anti-norovirus activity in cell culture using the mouse norovirus: Identification of active compounds
Introduction Human noroviruses (HuNoVs) infections are mostly acute and self-limiting, although chronic norovirus infections occur in patients with an immunodeficient state.1–3 Despite the yearly global impact of ∼700 million HuNoV infections, 219,000 deaths and 60 billion dollars in societal costs there is no specific antiviral therapies to treat (chronic) norovirus gastroenteritis.
Vaccines: from smallpox to technologies of the future
Do you want to broaden your knowledge on vaccinology or get a first well-balanced introduction to different aspects of the vaccine field? Then tune in for this MOOC! Do you know vaccines have proven to be one of the most powerful and effective ways of reducing morbidity and mortality and even eradicating diseases? Within this MOOC, we will elaborate on the burden of some infectious diseases. Besides the history of vaccines and the impact on mankind, a module will be dedicated to vaccine immunology.
Medical treatment options for COVID-19
Introduction Approximately 15% of coronavirus disease 2019 (COVID-19) patients will develop severe lung disease. It is thought that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) results in an acute respiratory infection that is cleared in most cases by the immune system after 7 to 14 days.1 The severe lung pathology that follows in a subset of patients after this acute viral stage is characterised by systemic inflammation reactions.
In Vitro Inhibition of Severe Acute Respiratory Syndrome Coronavirus by Chloroquine
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Novel symmetrical phenylenediamines as potential anti-hepatitis C virus agents
Despite the great progress made in the last 10 years, alternative strategies might help improving definitive treatment options against hepatitis C virus infection.
Experimenteel middel tegen hepatitis C remt infectie met zikavirus af bij muizen
Nadat het virus uitbrak op eilanden in de Stille Zuidzee en zich in 2015 en 2016 snel verspreidde naar Zuid- en Centraal-Amerika en de Caraïben, riep de Wereldgezondheidsorganisatie in februari 2016 de noodtoestand uit om de epidemie zo snel mogelijk te kunnen indijken. Er is immers nog geen vaccin of antiviraal middel beschikbaar om een infectie te voorkomen of behandelen. Het laboratorium van professor Neyts ontwikkelde vroeger al werkzame antivirale middelen tegen het hepatitis C-virus.
Gale Academic OneFile - Document - Antiviral treatment is more effective than smallpox vaccination upon lethal monkeypox virus infection
Citation metadata Document controls Main content Full Text: Author(s): Koert J. Stittelaar [1]; Johan Neyts [3]; Lieve Naesens [3]; Geert van Amerongen [1, 4]; Rob F. van Lavieren [5]; Antonin Holý [6]; Erik De Clercq [3]; Hubert G. M. Niesters [1]; Edwin Fries [1]; Chantal Maas [1]; Paul G. H. Mulder [2]; Ben A. M. van der Zeijst [4]; Albert D. M. E. Osterhaus (corresponding author) [1] There is concern that variola virus, the aetiological agent of smallpox, may be used as a biological weapon.
In vitro inhibition of severe acute respiratory syndrome coronavirus by chloroquine
Results and discussion In this study we report the in vitro antiviral activity of chloroquine against SARS-CoV Frankfurt 1 strain infection. Cytotoxicity in Vero E6 cells was measured in parallel with the antiviral activity. This experiment, done in quadruplicate, was repeated three times, and representative results are shown in Fig. 1 . SARS-CoV-infected Vero E6 cells were incubated for three days in the presence of 0, 0.8, 4, 20, and 100 μM chloroquine. Data are mean values ± SE of four replicates.
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