Biology subjects

Haase, A.

Publications and source records attributed to Haase, A..

At least 19 recordsLinked to original sources

bioRxiv2026

3-Hydroxypropanamidines: from antiplasmodial leads to a novel antibacterial scaffold

Arylamino alcohols constitute an established class of antimalarial agents. While this class is best known for its potent antiplasmodial activity, selected members, most notably mefloquine, have also been reported to exhibit antibacterial activity. Structurally related 3-hydroxypropanamidines were developed as highly potent antimalarial agents. Here, we explored the antibacterial activity of three 3-hydroxypropanamidines (4 (BLK278), 5 (BLK280), and 6 (TKK088)) against clinically relevant Gram-positive and Gram-negative bacteria and investigated their cytotoxicity, in vitro pharmacokinetic properties, and proteome-based bacterial response to treatment. We observed good antibacterial activity against Staphylococcus aureus, with 6 (TKK088) displaying the highest activity against multidrug-resistant MRSA and VISA strains. 5 (BLK280) demonstrated the greatest spectrum of activity acting also against clinically relevant Gram-negative strains of Escherichia coli, Acinetobacter baumannii, Klebsiella pneumoniae, Klebsiella aerogenes, and Shigella sonnei. In cytotoxicity assays with HUVEC and HAOSMC cells, 4 (BLK278) and the previously reported 7 (TKK129) showed the most favourable overall profiles among the investigated 3-hydroxypropanamidines. The selectivity indices for S. aureus were below 2.5 with clear cell-type-dependent differences for all compounds including mefloquine, suggesting that improving antibacterial selectivity is an important objective for further optimization. In vitro pharmacokinetics showed high plasma protein binding and good human microsomal and plasma stability for all three 3-hydroxypropanamidines. Gel-based proteomic responses revealed a strong impact on the bacterial cell envelope. The observed acute proteomic responses reflect pleiotropic effects and are consistent with earlier reports implicating F0F1-ATPase as a potential molecular target of mefloquine in Streptococcus pneumoniae.

microbiology↗

bioRxiv2026

Experimental platform to study the neuronal mechanisms of magnetoreception in the honey bee.

Honey bees (Apis mellifera) offer an alternative model for investigating magnetoreception, exhibiting reliable navigation and behavioral responses to magnetic fields. Thanks to their compact brains, well-matched to the penetration depth of modern optical imaging techniques, they may offer insights into the neural and biochemical mechanisms underlying this sense, something that standard models, like migrating birds, have not so far provided. But also in honeybees, this progress requires tools capable of resolving weak, magnetically induced neural activity with high spatio-temporal precision. The approach, presented here, bridges quantum biology and neuroscience, allowing for testing the radical pair mechanism (RPM) as a potential basis for magnetic sensing. As the RPM predicts that magnetoreception is coupled to the visual system, we developed an in vivo two-photon calcium imaging approach to measure neural activity in the anterior optic tubercle, a higher-order visual center involved in chromatic processing and potentially navigation. Bees were prepared using a minimally invasive technique, in which this neuropil was retrogradely labelled with a fluorescent calcium indicator, enabling stable recording conditions over several hours. Controlled blue-light stimuli were provided by the scattered output of a fiber laser, and weak magnetic-field stimuli were applied by a shielded, three-axis Helmholtz coil system that allowed precise modulation of field strength and polarity while minimizing electromagnetic interference. Visual stimulation evoked consistent and reproducible calcium responses, validating the preparation and imaging stability. Magnetic stimulation produced small fluorescence decreases, suggesting field-dependent modulation of neural activity. The developed imaging framework shows the feasibility of detecting magnetic modulation in vision- and navigation-related brain regions, suggesting neural amplification of weak magnetic cues and providing a platform for controlled tests of RPM-specific predictions, including light dependence, polarity independence, and radiofrequency perturbation.

neuroscience↗

bioRxiv2024

Neuronal correlates of sleep in honey bees

Honey bees Apis mellifera follow the day-night cycle for their foraging activity, entering rest periods during darkness. Despite considerable research on sleep behaviour in bees, its underlying neurophysiological mechanisms are not well understood, partly due to the lack of brain imaging data that allow for analysis from a network- or system-level perspective. This study aims to fill this gap by investigating whether neuronal activity during rest periods exhibits stereotypic patterns comparable to sleep signatures observed in vertebrates. Using two-photon calcium imaging of the antennal lobes (AL) in head-fixed bees, we analysed brain dynamics across motion and rest epochs during the nocturnal period. The recorded activity was computationally characterised, and machine learning was applied to determine whether a classifier could distinguish the two states after motion correction. Out-of-sample classification accuracy reached 93%, and a feature importance analysis suggested network features to be decisive. Accordingly, the glomerular connectivity was found to be significantly increased in the rest-state patterns. A full simulation of the AL using a leaky spiking neural network revealed that such a transition in network connectivity could be achieved by weakly correlated input noise and a reduction of synaptic conductance of the inhibitive local neurons (LNs) which couple the AL network nodes. The difference in the AL response maps between awake- and sleep-like states generated by the simulation showed a decreased specificity of the odour code in the sleep state, suggesting reduced information processing during sleep. Since LNs in the bee brain are GABAergic, this suggests that the GABAergic system plays a central role in sleep regulation in bees as in many higher species including humans. Our findings provide the first evidence that sleep-related network modulation mechanisms may be conserved throughout evolution, highlighting the bees potential as an invertebrate model for studying sleep at the level of single neurons.

neuroscience↗

bioRxiv2024

Differential coding of fruit, leaf, and microbial odours in the brains of Drosophila suzukii and Drosophila melanogaster.

The fly Drosophila suzukii, a close relative of D. melanogaster severely damages the production of berry and stone fruits in large parts of the world. Unlike D. melanogaster, which reproduces on overripe and fermenting fruits on the ground, D. suzukii prefers to lay its eggs in ripening fruits still on the plants. Flies locate fruit hosts by their odorant volatiles, which are detected and encoded by a highly specialized olfactory system before being translated into behaviour. The exact information processing pathway is not yet fully understood, especially the evaluation of odour attractiveness. It is also unclear what differentiates the brains of D. suzukii and D. melanogaster to cause the crucial difference in host selection. We hypothesized that the basis for different behaviours is already formed at the level of the antennal lobe of D. suzukii and D. melanogaster, by different neuronal responses to volatiles associated with ripe and fermenting fruit. We thus investigated by 3D in vivo two-photon calcium imaging how both species encoded odours from ripe fruits, leaves, fermented fruits, bacteria, and their mixtures in the antennal lobe. We then assessed their behavioural responses to mixtures of ripe and fermenting odours. The neural responses reflect species-dependent shifts in the odour code. In addition to this, morphological differences were also observed. Yet this was not directly reflected in different behavioural responses to the odours tested.

neuroscience↗

bioRxiv2024

Dynamic co-evolution of transposable elements and the piRNA pathway in African cichlid fishes

East African cichlid fishes have diversified in an explosive fashion, but the (epi)genetic basis of the phenotypic diversity of these fishes remains largely unknown. Although transposable elements (TEs) have been associated with phenotypic variation in cichlids, little is known about their transcriptional activity and epigenetic silencing. Here, we describe dynamic patterns of TE expression in African cichlid gonads and during early development. Orthology inference revealed an expansion of piwil1 genes in Lake Malawi cichlids, likely driven by PiggyBac TEs. The expanded piwil1 copies have signatures of positive selection and retain amino acid residues essential for catalytic activity. Furthermore, the gonads of African cichlids express a Piwi-interacting RNA (piRNA) pathway that target TEs. We define the genomic sites of piRNA production in African cichlids and find divergence in closely related species, in line with fast evolution of piRNA-producing loci. Our findings suggest dynamic co-evolution of TEs and host silencing pathways in the African cichlid radiations. We propose that this co-evolution has contributed to cichlid genomic diversity.

evolutionary biology↗

bioRxiv2024

Cell therapy with human iPSC-derived cardiomyocyte aggregates leads to efficient engraftment and functional recovery after myocardial infarction in non-human primates

BackgroundFunctionally coupled large myocardial grafts and a remarkable improvement of heart function in nonhuman primate models of myocardial infarction have been reported after transplantation of human embryonic stem cell-derived cardiomyocytes at relatively high numbers of up to 109 single cell cardiomyocytes - a dose equivalent to total cell loss after myocardial infarction in [~]10 times larger human hearts. To overcome apparent limitations associated with the application of single cells, this pre-clinical study investigated the injection of cardiomyocyte aggregates instead. MethodsHuman iPSC-derived cardiomyocyte aggregates were produced in scalable suspension culture. Intramyocardial injection of the aggregates into cynomolgus monkey hearts was conducted two weeks after myocardial infarction induced by permanent coronary artery ligation. Human cell engraftment was assessed after two weeks or three months; functional analyses included continuous telemetric ECG recording and repeated cardiac MRI assessment in comparison to sham treated animals. ResultsTreatment with cell numbers as low as 5 x 107 resulted in efficient structural engraftment. Notably, the degree of heart function recovery in vivo seemed to correlate with the contractility of the applied cardiomyocytes tested by parallel experiments in vitro. Graft-induced non-life-threatening arrhythmias were transient and decreased considerably during the three months follow-up. ConclusionsTransplantation of human iPSC-derived cardiomyocyte aggregates yielded comparable results to the reported application of higher numbers of single cell cardiomyocytes from human ESC, suggesting that the application of cardiomyocyte aggregates facilitates cell therapy development by reducing cell production costs and clinical risks associated with the administration of relatively high cell numbers. Clinical PerspectiveWhat is new? O_LIIn contrast to previously applied single cells, human iPSC-derived cardiomyocyte aggregates (hiCMAs) were transplanted in a non-human primate (NHP) model of MI, to reduce the required cell dose, promote myocardial retention of the graft, and limit the risks for adverse effects. Such low-dose treatment with almost pure ventricular cardiomyocytes produced under GMP-compliant conditions, resulted in the formation of relative large, structurally integrated human grafts in NHP hearts. C_LIO_LITransient non-life-threatening arrhythmias associated with intramyocardial cell transplantation decreased considerably during the three months follow-up. C_LIO_LIA remarkable recovery of left ventricular function was observed. This recovery notably correlated with the in vitro contractility of transplanted cardiomyocyte batches tested in bioartificial cardiac tissues (BCTs), underlining the relevance of a suitable potency assay. C_LI What are the clinical implications? O_LIIntra-myocardial injection of hiCMAs is a promising treatment modality for the recovery of contractile function after MI; their advanced production, storage and testing revealed in the study facilitate the clinical translation of hiPSC-based heart repair. C_LIO_LIThe need for relatively low numbers of cardiomyocytes produced through advanced protocols for scalable suspension culture reduces production costs of adequate cell batches, thereby increasing treatment availability. In vitro testing of the produced cell batches is required to ensure treatment efficacy. C_LIO_LIClinical hiCMA injection can be considered reasonably safe, however, pharmacological prevention and treatment of arrhythmias is required and temporary implantation of a cardioverter-defibrillator (ICD) could be considered. C_LI

cell biology↗

bioRxiv2023

Evidence that the Isc Iron-Sulfur Cluster Biogenesis Machinery Delivers Iron for -Cofactor Biosynthesis in Escherichia coli

[NiFe]-hydrogenases have a bimetallic NiFe(CN)2CO cofactor in their large, catalytic subunit. The 136 Da Fe(CN)2CO group of this cofactor is assembled on a distinct HypC-HypD scaffold complex prior to delivery to the apo-catalytic subunit, but the intracellular source of the iron ion is unresolved. Native mass spectrometric (native MS) analysis of HypCD complexes defined the [4Fe-4S] cluster associated with HypD and identified +26 - 28 Da and +136 Da modifications specifically associated with HypC. A HypCC2A variant dissociated from its complex with native HypD lacked all modifications. HypC dissociated from HypCD complexes isolated from Escherichia coli strains deleted for the iscS or iscU genes, encoding core components of the Isc iron-sulfur cluster biogenesis machinery, specifically lacked the +136 Da modification; however, it was retained on HypC isolated from suf mutants. The presence or absence of the +136 Da modification on the HypCD complex correlated with the hydrogenase enzyme activity profiles of the respective mutant strains. Notably, the [4Fe-4S] cluster on HypD was identified in all HypCD complexes analyzed. These results suggest that the iron of the Fe(CN)2CO group on HypCD derives from the Isc machinery, while either the Isc or the Suf machinery can deliver the [4Fe-4S] cluster to HypD.

microbiology↗

bioRxiv2023

Temporal dynamics of honeybee learning and decision-making are revealed by a novel automated PER system

The proboscis extension response (PER) has been widely used for decades to evaluate honeybees (Apis mellifera) learning and memory abilities. This classical conditioning paradigm is traditionally administered manually, and produces a binary score for each subject depending on the presence or absence of the proboscis extension in response to a stimulus - typically an odor which has been associated with a sucrose reward - to classify whether or not the bee has learned the association. Here we present a fully automated PER system which delivers stimuli in a more controlled manner, and thus standardizes the protocol within and between labs; further, the AI-facilitated behavioral scoring reduces human error and allows us to extract a richer meaning from the outcome. The automated frame-by-frame assessment goes beyond the binary classification of "learned" or "not learned", expanding the possibilities for many other measures. Using this method, we investigate the real-time decision-making processes of honeybees faced with difficult learning tasks. When posed with a quantitative (rather than qualitative, as in the case of different odors) PER association, honeybees show a pattern of rapid generalization to both the rewarded and non-rewarded stimuli, followed by a slowly acquired discrimination between the two. Our work lays the foundation for deeper exploration of the honeybee cognitive processes when posed with complex learning challenges.

neuroscience↗

bioRxiv2022

Cerebral organoids expressing mutant actin genes reveal cellular mechanism underlying microcephalic cortical malformation

Actins are structural cytoskeletal proteins playing crucial roles in multiple cellular processes. Mutations in the ACTB and ACTG1 genes, encoding the ubiquitous beta- and gamma- cytoskeletal actin isoforms, respectively, cause a broad spectrum of neurodevelopmental disorders, with microcephaly as the most frequent one. Here we used patient-derived cerebral organoids to gain insight into the pathogenesis underlying this cortical malformation. Cerebral organoids from induced pluripotent stem cells (iPSCs) of patients with the Baraitser-Winter- CerebroFrontoFacial syndrome (BWCFF-S), expressing either an ACTB or an ACTG1 missense mutation, are reduced in size, showing a thinner ventricular zone (VZ). This decrease in VZ progenitors is in turn associated with a striking change in the orientation of their cleavage plane from predominantly vertical (control) to predominantly horizontal (BWCFF-S), which is incompatible with increasing VZ progenitor abundance. Various cytoskeletal and morphological irregularities of BWCFF-S VZ progenitors, notably in the apical region of these cells, seemingly contribute to their predominantly horizontal cleavage plane orientation. Our results provide insight into the cell biological basis of the microcephaly associated with BWCFF-S caused by actin mutations.

neuroscience↗

bioRxiv2022

Network plasticity in the honey bee antennal lobe during odor presentation

Odorant processing presents multiple parallels across animal species, and insects became relevant models for the study of olfactory coding because of the tractability of the underlying neural circuits. Within the insect brain, odorants are received by olfactory sensory neurons and processed by the antennal lobe network. Such a network comprises multiple nodes, named glomeruli, that receive sensory information and are interconnected by local interneurons participating in shaping the neural representation of an odorant. The study of functional connectivity between the nodes of a sensory network in vivo is a challenging task that requires simultaneous recording from multiple nodes at high temporal resolutions. Here, we used fast two-photon microscopy to follow the calcium dynamics of antennal lobe glomeruli and applied Granger causality analysis to assess the functional directed connectivity among network nodes during and after olfactory stimulation. Our findings show that there is a significant causal coupling between network nodes also in the absence of olfactory stimulation. However, connectivity patterns change upon odorant arrival, showing an increase in connection density and conveying odorant-specific information. Furthermore, we show that causal functional connectivity is unique in individual subjects, and cannot be detected upon artificial glomerular scrambling across individuals. This demonstrates that network states do not consist solely of correlations of mean glomerular responses, which are known to be conserved across bees.

neuroscience↗

bioRxiv2022

Neural correlates for neonicotinoid-induced impairment of olfactory long-term memory

Reports of olfactory learning and memory deficits in honey bees exposed to neonicotinoid pesticides have been accumulating over the past decades. As agonists of the nicotinic receptors to acetylcholine, neonicotinoids target most of the projection neurons conveying olfactory information to the memory brain centres, the mushroom bodies (MBs). However, the neural mechanisms by which neonicotinoids interfere with memory formation are poorly understood. Here, we investigated the consequences of chronic exposure to the neonicotinoid imidacloprid on the number of projection neuron terminal boutons and on their plasticity in the context of long-term memory formation. Using super-resolution STED microscopy, we also measured the density of synapsin-positive units (SPUs) within boutons, as synapsin is known to be enriched in new boutons following neuronal activation. We show that imidacloprid suppresses the synaptic pruning of projection neurons naturally occurring with age and experience. The resulting excessive number of boutons in the MBs of treated bees was associated with long-term memory deficits. The subset of treated bees that showed successful memory formation had a similar number of boutons as untreated bees, suggesting that synaptic pruning might have been involved in the memorization process. As the SPU density was not affected by the imidacloprid treatment, the high bouton number in the lip of treated bees was not due to synaptogenesis. Altogether, our experiments show that, by altering synaptic pruning, imidacloprid interferes with long-term memory formation.

neuroscience↗

bioRxiv2022

Multisite imaging of neural activity using a genetically encoded calcium sensor in the honey bee Apis mellifera

Understanding of the neural bases for complex behaviors in Hymenoptera insect species has been limited by a lack of tools that allow measuring neuronal activity simultaneously in different brain regions. Here, we developed the first pan-neuronal genetic driver in a Hymenopteran model organism, the honey bee, and expressed the calcium indicator GCaMP6f under the control of the honey bee synapsin promoter. We show that GCaMP6f is widely expressed in the honey bee brain, allowing to record neural activity from multiple brain regions. To assess the power of this tool, we focused on the olfactory system, recording simultaneous responses from the antennal lobe, and from the more poorly investigated lateral horn and mushroom body calyces. Neural responses to 16 distinct odorants demonstrate that odorant quality (chemical structure) and quantity are faithfully encoded in the honey bee antennal lobe. In contrast, odor coding in the lateral horn departs from this simple physico-chemical coding, supporting the role of this structure in coding the biological value of odorants. We further demonstrate robust neural responses to several bee pheromone odorants, key drivers of social behavior, in the lateral horn. Combined, these brain recordings represent the first use of a neurogenetic tool for recording large-scale neural activity in a eusocial insect, and will be of utility in assessing the neural underpinnings of olfactory and other sensory modalities and of social behaviors and cognitive abilities.

neuroscience↗

bioRxiv2022

All-optical manipulation of the Drosophila olfactory system.

Thanks to its well-known neuroanatomy, limited brain size, complex behaviour, and extensive genetic methods, Drosophila has become an indispensable model in neuroscience. A vast number of studies have focused on its olfactory system and the processing of odour information. Optogenetics is one of the recently developed genetic tools that significantly advance this field of research, allowing to replace odour stimuli by direct neuronal activation with light. This becomes a universal all-optical toolkit when spatially selective optogenetic activation is combined with calcium imaging to read out neuronal responses. Initial experiments showed a successful implementation to study the olfactory system in fish and mice, but the olfactory system of Drosophila has been so far precluded from an application. To fill this gap, we present here optogenetic tools to selectively stimulate functional units in the Drosophila olfactory system, combined with two-photon calcium imaging to read out the activity patterns elicited by these stimuli at different levels of the brain. This method allows to study the spatial and temporal features of the information flow and reveals the functional connectivity in the olfactory network.

neuroscience↗

bioRxiv2021

Geosmin suppresses defensive behaviour and elicits unusual neural responses in honey bees.

Geosmin is an odorant produced by bacteria in moist soil. It has been found to be extraordinarily relevant to some insects, but the reasons for this are not yet fully understood. Here we report the first tests of the effect of geosmin on honey bees. A stinging assay showed that the defensive behaviour elicited by the bees alarm pheromone is strongly suppressed by geosmin. Surprisingly, the suppression is, however, only present at very low geosmin concentrations, and completely disappears at higher concentrations. We investigated the underlying mechanisms of the behavioural change at the level of the olfactory receptor neurons by means of electroantennography and at the level of the antennal lobe output via calcium imaging. Unusual effects were observed at both levels. The responses of the olfactory receptor neurons to mixtures of geosmin and the alarm pheromone component isoamyl acetate (IAA) were lower than to pure IAA, suggesting an interaction of both compounds at the olfactory receptor level. In the antennal lobe, the neuronal representation of geosmin showed a glomerular activation that decreased with increasing concentration, correlating well with the concentration dependence of the behaviour. Computational modelling of odour transduction and odour coding in the antennal lobe suggests that a broader than usual activation of different olfactory receptor types by geosmin in combination with lateral inhibition in the antennal lobe could lead to the observed non-monotonic increasing-decreasing responses to geosmin and thus underlie the specificity of the behavioural response to low geosmin concentrations.

neuroscience↗

bioRxiv2021

Targeted biallelic integration of an inducible Caspase 9 suicide gene for safer iPSC-based cellular therapies

Drug-inducible suicide systems may help to minimize risks of cellular therapies due to the tumor forming potential of human induced pluripotent stem cells (hiPSCs). Recent research challenged the usefulness of such systems since rare drug-resistant subclones were observed that showed elimination or silencing of the transgene. We have introduced a drug-inducible Caspase9 suicide system (iCASP9) into the AAVS1 safe harbor locus of hiPSCs. In these cells, apoptosis could be efficiently induced in vitro. In mice, drug treatment generally led to rapid elimination of teratomas, but individual animals subsequently formed tumor tissue from monoallelic iCASP9 hiPSCs. Very rare drug-resistant subclones of monoallelic iCASP9 hiPSCs appeared in vitro with frequencies of ~ 3x10-8. Transgene elimination, presumably via Loss of Heterozygosity (LoH), or methylation of the CAG promoter but not methylation of the O_SCPLOWPPPC_SCPLOWO_SCPCAP1C_SCPCAPO_SCPLOWRC_SCPLOWO_SCPCAP12C_SCPCAPO_SCPLOWCC_SCPLOW locus were identified as underlying mechanisms. In contrast, we never observed any escapees from biallelic iCASP9 hiPSCs, even after treatment of up to 0.8 billion hiPSCs. In conclusion, biallelic integration of an iCASP9 system in the AAVS1 locus may substantially contribute to the safety level of iPSC-based therapies, which should be calculated by relating clonal escapee frequencies to the cell number in tumors of a size that is readily detectable during routine screening procedures.

molecular biology↗

bioRxiv2021

Parallel processing of olfactory and mechanosensory information in the honeybee antennal lobe.

We report that airflow produces a complex activation pattern in the antennal lobes of the honeybee Apis mellifera. Glomerular response maps provide a stereotypical code for the intensity and the dynamics of mechanical stimuli that is superimposed on the olfactory code. We show responses to modulated stimuli suggesting that this combinatorial code could provide information about the intensity, direction, and dynamics of the airflow during flight and waggle dance communication.

neuroscience↗

bioRxiv2020

Reprogramming enriches for somatic cell clones with small scale mutations in cancer-associated genes

Recent studies demonstrated that the mutational load in human induced pluripotent stem cells (hiPSCs) is largely derived from their parental cells, but it is still unknown whether reprogramming may enrich for individual mutations. 30 hiPSC lines were analyzed by whole exome sequencing. High accuracy amplicon sequencing showed that all analyzed small scale variants pre-existed in their parental cells and that individual mutations present in small subpopulations of parental cells become enriched among hiPSC clones during reprogramming. Among those, putatively actionable driver mutations affect genes related to cell cycle control, cell death and pluripotency, and may confer a selective advantage during reprogramming. Finally, a shRNA-based experimental approach was applied to provide additional evidence for the individual impact of such genes on the reprogramming efficiency. In conclusion, we show that enriched mutations in curated onco- and tumor suppressor genes may account for an increased tumor risk and impact the clinical value of patient-derived hiPSCs.

genomics↗

bioRxiv2020

Biophysical modeling of the SARS-CoV-2 viral cycle reveals ideal antiviral targets

Effective therapies for COVID-19 are urgently needed. Presently there are more than 800 COVID-19 clinical trials globally, many with drug combinations, resulting in an empirical process with an enormous number of possible combinations. To identify the most promising potential therapies, we developed a biophysical model for the SARS-CoV-2 viral cycle and performed a sensitivity analysis for individual model parameters and all possible pairwise parameter changes (162 = 256 possibilities). We found that model-predicted virion production is fairly insensitive to changes in most viral entry, assembly, and release parameters, but highly sensitive to some viral transcription and translation parameters. Furthermore, we found a cooperative benefit to pairwise targeting of transcription and translation, predicting that combined targeting of these processes will be especially effective in inhibiting viral production.Competing Interest StatementThe authors have declared no competing interest.View Full Text

systems biology↗