Biology subjects

Todt, D.

Publications and source records attributed to Todt, D..

At least 19 recordsLinked to original sources

bioRxiv2026

Impact of hepatitis E virus host- and virus-derived insertions on the antiviral response in primary human hepatocytes

Despite the global burden of hepatitis E virus (HEV) infection, host-virus interactions underlying HEV pathogenesis and progression to chronicity remain incompletely understood. This study aimed to characterize the host transcriptomic response to infection with HEV variants harboring different host- and virus-derived insertions in the hypervariable region (HVR), with a focus on innate immune activation. We performed bulk RNA sequencing on PHHs from three donors infected with in vivo-identified HEV-3 variants harboring different HVR insertions (RPS17, HVR duplication, SERPINA1, TRIM22). To compare their replication fitness, we quantified progeny virus titers and viral RNA reads in the cellular transcriptome. Host transcriptomic responses were analyzed in detail at multiple time points to assess virus-induced differential gene expression. To further characterize the response to HEV infection with different HVR insertion variants, we performed gene ontology analysis and identified individual HEV-induced genes. Progeny virus titers at 72 hours post infection (h p.i.) were comparable across all PHH donors and HVR insertion variants. Two donors mounted robust host responses to HEV infection, characterized by widespread gene deregulation and interferon stimulated gene (ISG) upregulation at 72 h p.i. The HVR duplication insertion variant consistently triggered a weaker host response compared to RPS17, SERPINA1 and TRIM22 variants, with significantly fewer differentially expressed genes and reduced ISG induction. Gene ontology term analysis revealed enrichment of antiviral pathways upon infection with the different insertion variants, which was less pronounced for the HVR duplication variant. These findings reveal that HEV HVR rearrangement variants elicit distinct host response patterns. Importantly, our results suggest a positive correlation of viral replication and host response induction. This indicates that the HVR may play a crucial role in shaping host-virus interactions.

molecular biology↗

bioRxiv2026

A sequence variation between two orthologues alters functional expression of the potassium channel Kesv of Ectocarpus siliculosus virus

The potassium channel Kesv encoded by the Ectocarpus siliculosus virus (Kesv 1) differs by seven amino acid residues from its host-derived homolog (Kesv 2), resulting from lysogenic integration. When expressed in Xenopus laevis oocytes, Kesv 1 displayed significantly higher ion conductance and functional expression than Kesv 2, as demonstrated by GFP fluorescence and voltage clamp measurements. This study provides the first structural and functional analysis of Kesv 2, uncovering key differences between the original and host-derived variant. The systematic residue substitutions - based on location- from Kesv 2 to the corresponding residues in Kesv 1 illustrated that two amino acid exchanges in close proximity to the pore region (Q61H and T66A), albeit not individually but in combination, significantly resulted in a loss-of-function phenotype in Kesv 1. AlphaFold predictions and subsequent molecular dynamics simulations did not reveal significant differences between Kesv 1 and Kesv 2 structural models, suggesting that the loss of function cannot be attributed to differences at the structural level. Instead, a reduced surface expression of Kesv 2, caused by the sequence modulations in the brown algal host, appears more plausible. Notably, the pharmacological profiling with Linopirdine and Sotalol highlights differences in drug sensitivity, establishing these minimalist channels (core channel structure without regulatory domains) as tractable models for dissecting novel fundamental principles of ion channel function and drug interaction, while highlighting key differences from more complex channel systems. Significance StatementPotassium channels are essential for cellular excitability, yet their large size and structural complexity limit our understanding of the core features underlying channel function. Here, we identified and established an orthologous model to compare the effects of evolutionarily acquired mutations in two voltage-sensing potassium channels-the viral potassium channel from Ectocarpus siliculosus virus (Kesv 1) and its host-homolog derivative (Kesv 2) as simplified model systems for understanding ion channel physiology and host-viral interactions. We provide the first functional characterization of Kesv 2 in Xenopus laevis oocytes using two-electrode voltage-clamp and site-directed mutagenesis, revealing that, despite sharing an identical SVGYG selectivity-filter motif and differing by only 7 residues, they exhibit distinct ion-conduction properties.

pharmacology and toxicology↗

bioRxiv2026

Yellow fever vaccine propagation in primary human hepatocytes triggers antiviral and cytolytic responses

Yellow fever virus (YFV) infection can cause severe-to-fatal liver damage in humans, while immunization with the attenuated 17D vaccine strain has an excellent safety record, priming protective host immunity in the absence of pathology. To investigate virus-host correlates associated with these differential clinical outcomes, we combined YFV genome-level evolutionary analyses with investigations of vaccine and virulent strain hepatotropism. Evolutionary analyses confirmed purifying selection is the dominant force driving global YFV genome divergence, with functional constraints associated with the YFV transmission cycle selecting against vaccine attenuating mutations in virulent strains. In immune deficient hepatoma cells, 17D exhibited enhanced early propagation, spreading and apoptosis induction when compared to virulent strains. Ex vivo infections performed in primary human hepatocytes (PHH) from multiple donors confirmed robust propagation of both 17D and virulent YFV strains. RNA-sequencing revealed consistent and shared induction of IFNB and IFNL1-4, modulating overlapping gene programs associated with antiviral responses, immunity, chemotaxis and inflammation, cell-death, metabolic reprogramming and protein translation. Subtle differences in virion production kinetics and the magnitude and tempo of PHH transcriptional responses were observed. Antiviral responses to 17D were activated earlier while responses to virulent YFV were delayed but enhanced, mirroring virus propagation kinetics. More broadly, cellular responses to YFV infection are likely dominated by paracrine IFN signalling, with enriched LRP1 expression coupled with impaired IFN production in PHH contributing to YFVs robust hepatotropism. In summary, we demonstrate comparable propagation kinetics and PHH transcriptional responses to vaccine and virulent YFV strains, highlighting impaired hepatotropism is not a correlate of vaccine attenuation. These data imply that unknown barriers restrict liver access and associated organ pathology upon vaccination with 17D.

microbiology↗

bioRxiv2023

Hepatitis C virus cell culture adaptive mutations enhance cell culture propagation by multiple mechanisms but boost antiviral responses in primary human hepatocytes

Hepatitis C virus (HCV) infection progresses to chronicity in the majority of infected individuals. Its high intra-host genetic variability enables HCV to evade the continuous selection pressure exerted by the host, contributing to persistent infection. Utilizing a cell culture adapted HCV population (p100pop) which exhibits increased replicative capacity in various liver cell lines, this study investigated virus and host determinants which underlie enhanced viral fitness. Characterization of a panel of molecular p100 clones revealed that cell culture adaptive mutations optimize a range of virus-host interactions, resulting in expanded cell tropism, altered dependence on the cellular co-factor micro-RNA 122 and increased rates of virus spread. On the host side, comparative transcriptional profiling of hepatoma cells infected either with p100pop or its progenitor virus revealed that enhanced replicative fitness correlated with activation of endoplasmic reticulum stress signaling and the unfolded protein response. In contrast, infection of primary human hepatocytes with p100pop led to a mild attenuation of virion production which correlated with a greater induction of cell-intrinsic antiviral defense responses. In summary, long-term passage experiments in cells where selective pressure from innate immunity is lacking improves multiple virus-host interactions, enhancing HCV replicative fitness. However, this study further indicates that HCV has evolved to replicate at low levels in primary human hepatocytes to minimize innate immune activation, highlighting that an optimal balance between replicative fitness and innate immune induction is key to establishing persistence. Author SummaryHCV infection remains a global health burden with 58 million people currently chronically infected. However, the detailed molecular mechanisms which underly persistence are incompletely defined. We utilized a long-term cell culture adapted HCV, exhibiting enhanced replicative fitness in different human liver cell lines, in order to identify molecular principles by which HCV optimizes its replication fitness. Our experimental data revealed that cell culture adaptive mutations confer changes in the host response and usage of various host factors. The latter allows functional flexibility at different stages of the viral replication cycle. However, increased replicative fitness resulted in an increased activation of the innate immune system, which likely poses boundary for functional variation in authentic hepatocytes, explaining the observed attenuation of the adapted virus population in primary hepatocytes.

molecular biology↗

bioRxiv2023

Targeting cellular cathepsins inhibits hepatitis E virus infection

Background and AimsThe hepatitis E virus (HEV) is estimated to be responsible for 70,000 deaths annually, yet therapy options remain limited. In the pursuit of effective antiviral therapies, targeting viral entry holds promise and has proven effective for other hepatotropic viruses. However, the precise mechanisms and host factors required during HEV entry remain unclear. Cellular proteases have emerged as a class of host factors required for viral surface protein activation and productive cell entry by many viruses. Hence, we investigated the functional requirement and therapeutic potentials of cellular proteases during HEV infection. Approach and ResultsUsing our recently established HEV cell culture model and subgenomic HEV replicons, we found that blocking lysosomal cathepsins (CTS) with small molecule inhibitors, impedes HEV infection without affecting replication. Most importantly, the pan-cathepsin inhibitor K11777 robustly suppressed HEV infections with an EC50 of [~] 0.01 nM. Inhibition by K11777, devoid of notable toxicity in hepatoma cells until micromolar concentrations, was also observed in differentiated HepaRG and ex vivo in primary human hepatocytes. Furthermore, through time-of-addition experiments, we confirmed that HEV entry is potently blocked by inhibition of cathepsins and cathepsin L (CTSL) knockout cells were less permissive to HEV suggesting that CTSL is critical for HEV infection. ConclusionsIn summary, our study highlights the pivotal role of lysosomal cathepsins, especially CTSL, in the HEV entry process. The profound anti-HEV efficacy of the pan-cathepsin inhibitor, K11777, especially with its notable safety profile in primary cells, further underscores its potential as a promising therapeutic candidate.

cell biology↗

bioRxiv2023

A high-content RNA-based imaging assay reveals integrin beta 1 as a cofactor for cell entry of non-enveloped hepatitis E virus

Hepatitis E virus (HEV) is a major cause of acute hepatitis and mainly transmitted faecal-orally. HEV particles in faeces are non-enveloped, while those in the blood possess a cell-derived lipid envelope. Despite being a global health concern, there is limited understanding of the steps in the HEV life cycle, particularly cell entry. A previous study proposed integrin alpha 3 (ITGA3) as a potential host factor for nHEV entry, but the {beta}-integrin partner that co-mediates HEV entry has not been described. To address this knowledge gap and resolve the existing controversies surrounding HEV cell entry, we developed an RNA-FISH-based high-content imaging assay alllowing investigation of the entry pathways of both naked and enveloped HEV particles. Our observations indicate that naked HEV particles interact with the surface receptor integrin beta 1 (ITGB1), which likely facilitates their trafficking through the recycling endosome. In contrast, enveloped HEV particles do not interact with ITGB1 and instead use the classical endocytic pathway via the early endosome. Importantly, both forms of HEV require endosomal acidification and proteolytic cleavage by lysosomal cathepsins, which ultimately results in delivery of the HEV genome to the cytoplasm.

microbiology↗

bioRxiv2023

Spatiotemporal analysis of SARS-CoV-2 infection reveals an expansive wave of monocyte-derived macrophages associated with vascular damage and virus clearance in hamster lungs

Factors of the innate immune response to SARS-CoV-2 in the lungs are pivotal for the ability of the host to deal with the infection. In humans, excessive macrophage infiltration is associated with disease severity. Using 3D spatiotemporal analysis of optically cleared hamster lung slices in combination with virological, immunohistochemical and RNA sequence analyses, we visualized the spread of SARS-CoV-2 through the lungs and the rapid anti-viral response in infected lung epithelial cells, followed by a wave of monocyte-derived macrophage (MDM) infiltration and virus elimination from the tissue. These SARS-CoV-2 induced innate immune processes are closely related to the onset of necrotizing inflammatory and consecutive remodelling responses in the lungs, which manifests as extensive cell death, vascular damage, thrombosis, and cell proliferation. Here we show that MDM are directly linked to virus clearance, and appear in connection with tissue injury and blood vessel damage. Rapid initiation of prothrombotic factor upregulation, tissue repair and alveolar cell proliferation results in tissue remodelling, which is followed by fibrosis development despite a decrease in inflammatory and anti-viral activities. Thus, although the hamsters are able to resolve the infection following the MDM influx and repair lung tissue integrity, longer-term alterations of the lung tissues arise as a result of concurrent tissue damage and regeneration processes.

immunology↗

bioRxiv2022

SARS-CoV-2 entry route impacts a range of downstream viral and cellular processes

SARS-CoV-2 entry is promoted by both cell-surface TMPRSS2 and endolysosomal cathepsins. To investigate the impact of differentially routed virions on host and viral processes, lung epithelial cells expressing distinct combinations of entry factors were infected with authentic viruses. Entry route determined early rates of viral replication and transcription, egress and inhibitor sensitivity, with differences observed between virus strains. Transcriptional profiling revealed that induction of innate immunity was correlated to viral genome and transcript abundance in infected cells. Surface entry triggered early activation of antiviral responses, reducing cumulative virion production, while endolysosomal entry delayed antiviral responses and prolonged virus shedding due to extended cell viability. The likely molecular footprints of escape from antiviral effector targeting were also recorded in viral genomes and correlated with entry route-dependent immune status of cells. TMPRSS2 orthologues from diverse mammals, but not zebra fish, facilitated infection enhancement, which was more pronounced for ancestral strains. Leveraging RNA-seq and scRNA-seq datasets from SARS-CoV-2 infected hamsters, we validate aspects of our model in vivo. In summary, we demonstrate that distinct cellular and viral processes are linked to viral entry route, collectively modulating virus shedding, cell-death rates and viral genome evolution.

microbiology↗

bioRxiv2021

In contrast to TH2-biased approaches, TH1 COVID-19 vaccines protect Syrian hamsters from severe disease in the absence of dexamethasone-treatable vaccine-associated enhanced respiratory pathology

Since December 2019, the novel human coronavirus SARS-CoV-2 has spread globally, causing millions of deaths. Unprecedented efforts have enabled development and authorization of a range of vaccines, which reduce transmission rates and confer protection against the associated disease COVID-19. These vaccines are conceptually diverse, including e.g. classical adjuvanted whole-inactivated virus, viral vectors, and mRNA vaccines. We have analysed two prototypic model vaccines, the strongly TH1-biased measles vaccine-derived candidate MeVvac2-SARS2-S(H) and a TH2-biased Alum-adjuvanted, non-stabilized Spike (S) protein side-by-side, for their ability to protect Syrian hamsters upon challenge with a low-passage SARS-CoV-2 patient isolate. As expected, the MeVvac2-SARS2-S(H) vaccine protected the hamsters safely from severe disease. In contrast, the protein vaccine induced vaccine-associated enhanced respiratory disease (VAERD) with massive infiltration of eosinophils into the lungs. Global RNA-Seq analysis of hamster lungs revealed reduced viral RNA and less host dysregulation in MeVvac2-SARS2-S(H) vaccinated animals, while S protein vaccination triggered enhanced host gene dysregulation compared to unvaccinated control animals. Of note, mRNAs encoding the major eosinophil attractant CCL-11, the TH2 response-driving cytokine IL-19, as well as TH2-cytokines IL-4, IL-5, and IL-13 were exclusively up-regulated in the lungs of S protein vaccinated animals, consistent with previously described VAERD induced by RSV vaccine candidates. IL-4, IL-5, and IL-13 were also up-regulated in S-specific splenocytes after protein vaccination. Using scRNA-Seq, T cells and innate lymphoid cells were identified as the source of these cytokines, while Ccl11 and Il19 mRNAs were expressed in lung macrophages displaying an activated phenotype. Interestingly, the amount of viral reads in this macrophage population correlated with the abundance of Fc-receptor reads. These findings suggest that VAERD is triggered by induction of TH2-type helper cells secreting IL-4, IL-5, and IL-13, together with stimulation of macrophage subsets dependent on non-neutralizing antibodies. Via this mechanism, uncontrolled eosinophil recruitment to the infected tissue occurs, a hallmark of VAERD immunopathogenesis. These effects could effectively be treated using dexamethasone and were not observed in animals vaccinated with MeVvac2-SARS2-S(H). Taken together, our data validate the potential of TH2-biased COVID-19 vaccines and identify the transcriptional mediators that underlie VAERD, but confirm safety of TH1-biased vaccine concepts such as vector-based or mRNA vaccines. Dexamethasone, which is already in use for treatment of severe COVID-19, may alleviate such VAERD, but in-depth scrutiny of any next-generation protein-based vaccine candidates is required, prior and after their regulatory approval.

immunology↗

bioRxiv2021

Differential interferon-α subtype immune signatures suppress SARS-CoV-2 infection

Type I interferons (IFN-I) exert pleiotropic biological effects during viral infections, balancing virus control versus immune-mediated pathologies and have been successfully employed for the treatment of viral diseases. Humans express twelve IFN-alpha () subtypes, which activate downstream signalling cascades and result in distinct patterns of immune responses and differential antiviral responses. Inborn errors in type I IFN immunity and the presence of anti-IFN autoantibodies account for very severe courses of COVID-19, therefore, early administration of type I IFNs may be protective against life-threatening disease. Here we comprehensively analysed the antiviral activity of all IFN subtypes against SARS-CoV-2 to identify the underlying immune signatures and explore their therapeutic potential. Prophylaxis of primary human airway epithelial cells (hAEC) with different IFN subtypes during SARS-CoV-2 infection uncovered distinct functional classes with high, intermediate and low antiviral IFNs. In particular IFN5 showed superior antiviral activity against SARS-CoV-2 infection. Dose-dependency studies further displayed additive effects upon co-administered with the broad antiviral drug remdesivir in cell culture. Transcriptomics of IFN-treated hAEC revealed different transcriptional signatures, uncovering distinct, intersecting and prototypical genes of individual IFN subtypes. Global proteomic analyses systematically assessed the abundance of specific antiviral key effector molecules which are involved in type I IFN signalling pathways, negative regulation of viral processes and immune effector processes for the potent antiviral IFN5. Taken together, our data provide a systemic, multi-modular definition of antiviral host responses mediated by defined type I IFNs. This knowledge shall support the development of novel therapeutic approaches against SARS-CoV-2.

cell biology↗

bioRxiv2021

Comparable environmental stability and disinfection profiles of the currently circulating SARS-CoV-2 variants of concern B.1.1.7 and B.1.351

The emergence of novel SARS-CoV-2 B.1.1.7 and B.1.351 variants of concern with increased transmission dynamics has raised questions regarding stability and disinfection of these viruses. In this study, we analyzed surface stability and disinfection of the currently circulating SARS-CoV-2 variants B.1.1.7 and B.1.351 compared to the wildtype. Treatment with heat, soap and ethanol revealed similar inactivation profiles indicative of a comparable susceptibility towards disinfection. Furthermore, we observed comparable surface stability on steel, silver, copper and face masks. Overall, our data support the application of currently recommended hygiene concepts to minimize the risk of B.1.1.7 and B.1.351 transmission.

microbiology↗

bioRxiv2021

A realistic touch-transfer method reveals low risk of transmission for SARS-CoV-2 by contaminated coins and bank notes

The current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has created a significant threat to global health. While respiratory aerosols or droplets are considered as the main route of human-to-human transmission, secretions expelled by infected individuals can also contaminate surfaces and objects, potentially creating the risk of fomite-based transmission. Consequently, frequently touched objects such as paper currency and coins have been suspected as a potential transmission vehicle. To assess the risk of SARS-CoV-2 transmission by banknotes and coins, we examined the stability of SARS-CoV-2 and bovine coronavirus (BCoV), as surrogate with lower biosafety restrictions, on these different means of payment and developed a touch transfer method to examine transfer efficiency from contaminated surfaces to skin. Although we observed prolonged virus stability, our results, including a novel touch transfer method, indicate that the transmission of SARS-CoV-2 via contaminated coins and banknotes is unlikely and requires high viral loads and a timely order of specific events.

microbiology↗

bioRxiv2021

A genome-wide CRISPR screen identifies interactors of the autophagy pathway as conserved coronavirus targets

Over the past 20 years, the emergence of three highly pathogenic coronaviruses (CoV) - SARS-CoV, MERS-CoV, and most recently SARS-CoV-2 - has shown that CoVs pose a serious risk to human health and highlighted the importance of developing effective therapies against them. Similar to other viruses, CoVs are dependent on host factors for their survival and replication. We hypothesized that evolutionarily distinct CoVs may exploit similar host factors and pathways to support their replication cycle. Here, we conducted two independent genome-wide CRISPR/Cas9 knockout screens to identify pan-CoV host factors required for the replication of both endemic and emerging CoVs, including the novel CoV SARS-CoV-2. Strikingly, we found that several autophagy-related genes, including the immunophilin FKBP8, TMEM41B, and MINAR1, were common host factors required for CoV replication. Importantly, inhibition of the immunophilin family with the compounds Tacrolimus, Cyclosporin A, and the non-immunosuppressive derivative Alisporivir, resulted in dose-dependent inhibition of CoV replication in primary human nasal epithelial cell cultures that resemble the natural site of virus replication. Overall, we identified host factors that are crucial for CoV replication and demonstrate that these factors constitute potential targets for therapeutic intervention by clinically approved drugs.

microbiology↗

bioRxiv2021

Initial HCV infection of adult hepatocytes triggers a temporally structured transcriptional program containing diverse pro- and anti-viral elements

Transcriptional profiling provides global snapshots of virus-mediated cellular reprogramming, which can simultaneously encompass pro- and antiviral components. To determine early transcriptional signatures associated with HCV infection of authentic target cells, we performed ex vivo infections of adult primary human hepatocytes (PHHs) from seven donors. Longitudinal sampling identified minimal gene dysregulation at six hours post infection (hpi). In contrast, at 72 hpi, massive increases in the breadth and magnitude of HCV-induced gene dysregulation were apparent, affecting gene classes associated with diverse biological processes. Comparison with HCV-induced transcriptional dysregulation in Huh-7.5 cells identified limited overlap between the two systems. Of note, in PHHs, HCV infection initiated broad upregulation of canonical interferon (IFN)-mediated defense programs, limiting viral RNA replication and abrogating virion release. We further find that constitutive expression of IRF1 in PHHs maintains a steady-state antiviral program in the absence of infection, which can additionally reduce HCV RNA translation and replication. We also detected infection-induced downregulation of [~]90 genes encoding components of the EIF2 translation initiation complex and ribosomal subunits in PHHs, consistent with a signature of translational shutoff. As HCV polyprotein translation occurs independently of the EIF2 complex, this process is likely pro-viral: only translation initiation of host transcripts is arrested. The combination of antiviral intrinsic and inducible immunity, balanced against pro-viral programs, including translational arrest, maintains HCV replication at a low-level in PHHs. This may ultimately keep HCV under the radar of extra-hepatocyte immune surveillance while initial infection is established, promoting tolerance, preventing clearance and facilitating progression to chronicity. IMPORTANCEAcute HCV infections are often asymptomatic and therefore frequently undiagnosed. We endeavored to recreate this understudied phase of HCV infection using explanted PHHs and monitored host responses to initial infection. We detected temporally distinct virus-induced perturbations in the transcriptional landscape, which were initially narrow but massively amplified in breadth and magnitude over time. At 72 hpi, we detected dysregulation of diverse gene programs, concurrently promoting both virus clearance and virus persistence. On the one hand, baseline expression of IRF1 combined with infection-induced upregulation of IFN-mediated effector genes suppresses virus propagation. On the other, we detect transcriptional signatures of host translational inhibition, which likely reduces processing of IFN-regulated gene transcripts and facilitates virus survival. Together, our data provide important insights into constitutive and virus-induced transcriptional programs in PHHs, and identifies simultaneous antagonistic dysregulation of pro-and anti-viral programs which may facilitate host tolerance and promote viral persistence.

immunology↗

bioRxiv2020

Glycyrrhizin effectively neutralizes SARS-CoV-2 in vitro by inhibiting the viral main protease

The newly emerged coronavirus, which was designated as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the COVID-19 disease. High effective and well-tolerated medication for hospitalized and non-hospitalized patients is urgently needed. Traditional herbal medicine substances were discussed as promising candidates for the complementary treatment of viral diseases and recently suggested for the treatment of COVID-19. In the present study, we investigated aqueous licorice root extract for its neutralizing activity against SARS-CoV-2 in vitro, identified the active compound glycyrrhizin and uncovered the respective mechanism of viral neutralization. We demonstrated that glycyrrhizin, the primary active ingredient of the licorice root, potently neutralizes SARS-CoV-2 by inhibiting the viral main protease. Our experiments highlight glycyrrhizin as a potential antiviral compound that should be further investigated for the treatment of COVID-19.

molecular biology↗

bioRxiv2020

Virucidal efficacy of different formulations for hand and surface disinfection targeting SARS CoV-2

In the ongoing SARS CoV-2 pandemic effective measures are needed, and guidance based on the methodological framework of the European committee for standardization (CEN) can help to choose effective disinfectants on an immediate basis. This study demonstrates that two commercially available formulations for surface disinfection and one formulation for hand disinfection claiming "virucidal activity against enveloped viruses" are effectively inactivating SARS-CoV-2. This study emphasizes that chemical disinfectants claiming "virucidal activity against enveloped viruses" are an effective choice to target enveloped SARS-CoV-2 as a preventive measure.

microbiology↗

bioRxiv2020

Comparison of the in vitro-efficacy of different mouthwash solutions targeting SARS-CoV-2 based on the European Standard EN 14476

The SARS-Cov-2 pandemic is triggering a global health emergency alert, and recent research is indicating the relevance of aerosols in the spread of SARS-CoV-2. Thus, in this study antiseptic mouthwashes based on the actives chlorhexidine (CHX) and octenidine (OCT) were investigated regarding their efficacy against SARS-CoV-2 using EN 14476. Based on the requirement of EN 14476 (i.e. reduction of viral titer by [≥] 4 log 10), the OCT-based formulation was effective within only 15 sec against SARS-CoV-2, and thus constitutes an interesting candidate for future clinical studies to prove its effectiveness in a potential prevention of SARS-CoV-2 transmission by aerosols.

microbiology↗

bioRxiv2020

Holder Pasteurization Inactivates SARS-CoV-2 in Human Breast Milk

SARS-CoV-2 RNA has been detected in the human breast milk of infected mothers, raising concerns regarding the safety of breastfeeding upon infection. We here show that holder pasteurization inactivates SARS-CoV-2 and provides an alternative and safe option for infected mothers to continue feeding breast milk to their infants.

microbiology↗