Lisa Bauer's research while affiliated with Erasmus MC and other places

Publications (20)

Preprint
Full-text available
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with various neurological complications. SARS-CoV-2 infection induces neuroinflammation in the central nervous system (CNS), whereat the olfactory bulb seems to be involved most frequently. Here we show differences in the neuroinvasiveness and neurovirulence among...
Article
Full-text available
SARS-CoV-2 infection is associated with a diverse spectrum of neurological complications in the acute and post-acute stages. The pathogenesis of these complications is complex and dependent on many factors. For accurate and consistent interpretation of experimental data in this fast-growing field of research, it is essential to use terminology cons...
Article
Full-text available
Enteroviruses are globally prevalent human pathogens responsible for many diseases. The nonstructural protein 2C is a AAA+ helicase and plays a key role in enterovirus replication. Drug repurposing screens identified 2C-targeting compounds such as fluoxetine and dibucaine, but how they inhibit 2C is unknown. Here, we present a crystal structure of...
Article
The Front Cover shows bithiazole derivatives acting as broad‐spectrum antiviral agents (BSAAs) by targeting human host cells. These molecules block the replication of human rhinoviruses (hRVs) and Zika virus (ZIKV) via inhibition of the intracellular protein PI4KIIIβ while the inhibition of SARS‐CoV‐2 entry and replication seems to be connected wit...
Article
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Over half a century since the description of the first antiviral drug, “old” re‐emerging viruses and “new” emerging viruses still represent a serious threat for global health. Their high mutation rate and rapid selection of resistance towards common antiviral drugs, together with the increasing number of co‐infections, make the war against viruses...
Article
Full-text available
Infections with the recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are often associated with neurological complications. Evidence suggests that SARS-CoV-2 enters the brain via the olfactory nerve; however, SARS-CoV-2 is only rarely detected in the central nervous system of COVID-19 patients.
Article
Full-text available
COVID-19 is associated with a wide range of extrarespiratory complications, of which the pathogenesis is currently not fully understood. However, both systemic spread and systemic inflammatory responses are thought to contribute to the systemic pathogenesis. In this study, we determined the temporal kinetics of viral RNA in serum (RNAemia) and the...
Article
Full-text available
Animal models are an inimitable method to study the systemic pathogenesis of virus-induced disease. Extra-respiratory complications of influenza A virus infections are not extensively studied even though they are often associated with severe disease and mortality. Here we review and recommend mammalian animal models that can be used to study extra-...
Preprint
Full-text available
The enterovirus genus encompasses many clinically important human pathogens such as poliovirus, coxsackieviruses, echoviruses, numbered enteroviruses and rhinoviruses. These viruses are the etiological agents of several human diseases, including hand-foot-and-mouth disease, neonatal sepsis, encephalitis, meningitis, paralysis and respiratory infect...
Preprint
Full-text available
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is associated with a wide variety of neurological complications. Even though SARS-CoV-2 is rarely detected in the central nervous system (CNS) or cerebrospinal fluid, evidence is accumulating that SARS-CoV-2 might enter the CNS via the olfactory nerve. However, what happens afte...
Article
Full-text available
Enterovirus D68 (EV-D68) causes mild to severe respiratory disease and is associated with acute flaccid myelitis since 2014. Currently, the understanding of the ability of EV-D68 to replicate in the central nervous system (CNS), and whether it is associated with a specific clade of EV-D68 viruses or specific viral factors, is lacking. Comparing dif...
Preprint
Full-text available
Male sex belongs to one of the major risk factors for severe COVID-19 outcome. However, underlying mechanisms that could affect sex dependent disease outcome are yet unknown. Here, we identified the CYP19A1 gene encoding for the testosterone-to-estradiol metabolizing enzyme CYP19A1 (alias aromatase) as a male abundant host factor that contributes t...
Article
Enteroviruses (EV) are a group of positive-strand RNA (+RNA) viruses that include many important human pathogens (e.g. poliovirus, coxsackievirus, echovirus, numbered enteroviruses and rhinoviruses). Fluoxetine was identified in drug repurposing screens as potent inhibitor of enterovirus B and enterovirus D replication. In this paper we are reporti...
Article
Full-text available
RNA interference (RNAi) has strong antiviral activity in a range of animal phyla, but the extent to which RNAi controls virus infection in chordates, and specifically mammals remains incompletely understood. Here we analyze the antiviral activity of RNAi against a number of positive-sense RNA viruses using Argonaute-2 deficient human cells. In line...
Article
Full-text available
Enteroviruses (family Picornaviridae) comprise a large group of human pathogens against which no licensed antiviral therapy exists. Drug-repurposing screens uncovered the FDA-approved drug fluoxetine as replication inhibitor of enterovirus B and D species. Fluoxetine likely targets the non-structural viral protein 2C, but detailed mode-of-actions s...
Article
Full-text available
Itraconazole (ITZ) is a well-known, FDA-approved antifungal drug that is also in clinical trials for its anticancer activity. ITZ exerts its anticancer activity through several disparate targets and pathways. ITZ inhibits angiogenesis by hampering the functioning of the vascular endothelial growth receptor 2 (VEGFR2) and by indirectly inhibiting mT...
Article
Full-text available
Enteroviruses (e.g., poliovirus, enterovirus-A71, coxsackievirus, enterovirus-D68, rhinovirus) include many human pathogens causative of various mild and more severe diseases, especially in young children. Unfortunately, antiviral drugs to treat enterovirus infections have not been approved yet. Over the past decades, several direct-acting inhibito...
Article
Full-text available
Enteroviruses (EV) represent many important pathogens of humans. Unfortunately, no antiviral compounds currently exist to treat infections with these viruses. We screened the Prestwick Chemical Library®, a library of approved drugs, for inhibitors of coxsackievirus B3 and identified pirlindole as potent novel inhibitor and confirmed the inhibitory...

Citations

... We show that SARS-CoV-2 was not neuroinvasive following infection in an established hamster model despite evidence of mild microglial activation throughout the brain that was most evident in the hippocampal region. Recent studies available as pre-prints have also reported similar levels of microglial activation as indicated by increased levels of staining using antibodies to microglial proteins and changes in morphology [35,36]. Additionally, transcriptional changes indicative of mild neuroinflammation have been observed in the brains of hamsters infected with SARS-CoV-2 that differed depending on the variant [36]. ...
... Many studies have suggested that SARS-CoV-2 relies on its obligate receptor to enter cells (9). The canonical SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2), is the major entry receptor for SARS-CoV-2 in many cell types, such as nasal epithelial cells, endothelial cells, and pericytes (10). However, ACE2 expression is undetectable in cortical astrocytes pre-or postinfection. ...
... Grazia Martina et al. (2021) estimated the antiviral potency of the tested molecules towards coronavirus, a DYRA, association with cells infection in the appearance of repeated therapy dilutions, has been employed as earlier defined, towards slight variations. The bithiazole chemotype is a promising substrate for the design of BSAAs by targeting the host kinase machinery (PI4KIII) or certain targets, as seen here with SARS-CoV-2. ...
... Neural progenitor cells (NPCs) derive from human induced pluripotent stem cells (hiPSCs) and have been used in the "in vitro" studies to understand the viral life cycle, amplify, and isolate the virus. 87 These studies have shown that the SARS-CoV-2 can infect hiPSC cells in culture suggesting the possibility that the virus exerts a modulatory effect on the nervous and immune systems, but it is unable to produce copies of itself. Although many cellular models for studying SARS-CoV-2 infection have been developed, so far none of them allows us to understand the evolution of the neuronal damage observed in patients. ...
... In contrast, the association between IFN-b and pneumonia or RNAemia was not significant. Serum SARS-CoV-2 RNA viral load, recently termed as RNAemia, reflects the spread of SARS-CoV-2 into circulation, which has been reported as a potential predictor of unfavorable clinical outcomes in patients with COVID-19 (35)(36)(37). RNAemia, detected by qPCR, is observed in 1.5% to 50% of patients with a mild-to-severe COVID-19. These results support our findings (RNAemia was detected in 30% of patients with COVID-19). ...
... One of the proposed mechanisms is direct tissue damage caused by IAV or CoV infection as there is evidence that the viral receptors (sialic acids and ACE2, respectively) and transmembrane protease serine 2 (TMPRSS2) protease, which cleaves the surface glycoproteins (hemagglutinin and Spike, respectively), both required for viral entry, are expressed at extrapulmonary sites [106,107]. Immunohistochemistry detection of viral nucleic acids or antigens in extrapulmonary tissues has been reported on autopsy samples and in animal models [99,108,109]. However, the robustness and clinical relevance of these findings remains debatable. ...
... More importantly, the complex structures of 2C in complex with inhibitors can contribute significantly to the understanding of the mechanism of action of existing 2C inhibitors and guide the development of more potent and selective 2C inhibitors. It is noted that the X-ray crystal structure of CV-B3 2C in complex with (S)-fluoxetine was recently reported in a preprint (PDB: 6T3W) ( Fig. 7B and C) 130 . X-ray crystal structure showed that (S)-fluoxetine binds to the allosteric site in the CV-B3 2C (Fig. 7B and C), and drug binding stabilizes the 2C hexamer. ...
... Virus uses different strategies to survive the changeable environments. Enterovirus, like the majority of RNA viruses, employs the strategies of mutation to adapt the surroundings and implicate in pathogenesis [1][2][3][4]. As an important causative agent, enterovirus is a member of the genus of Enterovirus within the family of Picornaviridae. ...
... However, after 2014, viruses from subclade B3 became more prominent [17] and, to a lesser extent, D1 [13]. Although it was initially believed that the ability to cause CNS complications was clade-specific, studies have now shown that clade B3 isolates from the 2014 outbreak differ in their ability to cause CNS complications in vivo and replication efficiency in vitro, suggesting that the ability to invade and replicate in the CNS is not a clade-specific feature [18][19][20]. ...
... Some repurposed drugs such as fluoxetine (a selective serotonin reuptake inhibitor used as antidepressant drug) targeting non-structural viral 2C protein [27][28][29], itraconazole (an antifungal drug) targeting the non-structural viral protein 3A [30] or emetine (antiprotozoal drug) with inhibitory effect on IRES activity [31], were found to have anti-CVB activity. There is growing interest in studying antiviral activity of repurposed drugs as they may quickly enter into clinical trials. ...