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Article ; Online: Restriction factor screening identifies RABGAP1L-mediated disruption of endocytosis as a host antiviral defense.

Fernbach, Sonja / Spieler, Eva E / Busnadiego, Idoia / Karakus, Umut / Lkharrazi, Anouk / Stertz, Silke / Hale, Benjamin G

Cell reports

2022 Volume 38, Issue 12, Page(s) 110549

Abstract: Host interferons (IFNs) powerfully restrict viruses through the action of several hundred IFN-stimulated gene (ISG) products, many of which remain uncharacterized. Here, using RNAi screening, we identify several ISG restriction factors with previously ... ...

Abstract	Host interferons (IFNs) powerfully restrict viruses through the action of several hundred IFN-stimulated gene (ISG) products, many of which remain uncharacterized. Here, using RNAi screening, we identify several ISG restriction factors with previously undescribed contributions to IFN-mediated defense. Notably, RABGAP1L, a Tre2/Bub2/Cdc16 (TBC)-domain-containing protein involved in regulation of small membrane-bound GTPases, robustly potentiates IFN action against influenza A viruses (IAVs). Functional studies reveal that the catalytically active TBC domain of RABGAP1L promotes antiviral activity, and the RABGAP1L proximal interactome uncovered its association with proteins involved in endosomal sorting, maturation, and trafficking. In this regard, RABGAP1L overexpression is sufficient to disrupt endosomal function during IAV infection and restricts an early post-attachment, but pre-fusion, stage of IAV cell entry. Other RNA viruses that enter cells primarily via endocytosis are also impaired by RABGAP1L, while entry promiscuous SARS-CoV-2 is resistant. Our data highlight virus endocytosis as a key target for host defenses.
MeSH term(s)	Antiviral Agents ; COVID-19 ; Cell Line ; Endocytosis ; Humans ; SARS-CoV-2
Chemical Substances	Antiviral Agents
Language	English
Publishing date	2022-03-12
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2022.110549
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Article ; Online: Restriction factor screening identifies RABGAP1L-mediated disruption of endocytosis as a host antiviral defense

Sonja Fernbach / Eva E. Spieler / Idoia Busnadiego / Umut Karakus / Anouk Lkharrazi / Silke Stertz / Benjamin G. Hale

Cell Reports, Vol 38, Iss 12, Pp 110549- (2022)

2022

Abstract: Summary: Host interferons (IFNs) powerfully restrict viruses through the action of several hundred IFN-stimulated gene (ISG) products, many of which remain uncharacterized. Here, using RNAi screening, we identify several ISG restriction factors with ... ...

Abstract	Summary: Host interferons (IFNs) powerfully restrict viruses through the action of several hundred IFN-stimulated gene (ISG) products, many of which remain uncharacterized. Here, using RNAi screening, we identify several ISG restriction factors with previously undescribed contributions to IFN-mediated defense. Notably, RABGAP1L, a Tre2/Bub2/Cdc16 (TBC)-domain-containing protein involved in regulation of small membrane-bound GTPases, robustly potentiates IFN action against influenza A viruses (IAVs). Functional studies reveal that the catalytically active TBC domain of RABGAP1L promotes antiviral activity, and the RABGAP1L proximal interactome uncovered its association with proteins involved in endosomal sorting, maturation, and trafficking. In this regard, RABGAP1L overexpression is sufficient to disrupt endosomal function during IAV infection and restricts an early post-attachment, but pre-fusion, stage of IAV cell entry. Other RNA viruses that enter cells primarily via endocytosis are also impaired by RABGAP1L, while entry promiscuous SARS-CoV-2 is resistant. Our data highlight virus endocytosis as a key target for host defenses.
Keywords	CP: Microbiology ; CP: Immunology ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
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Article ; Online: Critically ill COVID-19 patients with neutralizing autoantibodies against type I interferons have increased risk of herpesvirus disease.

Busnadiego, Idoia / Abela, Irene A / Frey, Pascal M / Hofmaenner, Daniel A / Scheier, Thomas C / Schuepbach, Reto A / Buehler, Philipp K / Brugger, Silvio D / Hale, Benjamin G

PLoS biology

2022 Volume 20, Issue 7, Page(s) e3001709

Abstract: Autoantibodies neutralizing the antiviral action of type I interferons (IFNs) have been associated with predisposition to severe Coronavirus Disease 2019 (COVID-19). Here, we screened for such autoantibodies in 103 critically ill COVID-19 patients in a ... ...

Abstract	Autoantibodies neutralizing the antiviral action of type I interferons (IFNs) have been associated with predisposition to severe Coronavirus Disease 2019 (COVID-19). Here, we screened for such autoantibodies in 103 critically ill COVID-19 patients in a tertiary intensive care unit (ICU) in Switzerland. Eleven patients (10.7%), but no healthy donors, had neutralizing anti-IFNα or anti-IFNα/anti-IFNω IgG in plasma/serum, but anti-IFN IgM or IgA was rare. One patient had non-neutralizing anti-IFNα IgG. Strikingly, all patients with plasma anti-IFNα IgG also had anti-IFNα IgG in tracheobronchial secretions, identifying these autoantibodies at anatomical sites relevant for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Longitudinal analyses revealed patient heterogeneity in terms of increasing, decreasing, or stable anti-IFN IgG levels throughout the length of hospitalization. Notably, presence of anti-IFN autoantibodies in this critically ill COVID-19 cohort appeared to predict herpesvirus disease (caused by herpes simplex viruses types 1 and 2 (HSV-1/-2) and/or cytomegalovirus (CMV)), which has been linked to worse clinical outcomes. Indeed, all 7 tested COVID-19 patients with anti-IFN IgG in our cohort (100%) suffered from one or more herpesviruses, and analysis revealed that these patients were more likely to experience CMV than COVID-19 patients without anti-IFN autoantibodies, even when adjusting for age, gender, and systemic steroid treatment (odds ratio (OR) 7.28, 95% confidence interval (CI) 1.14 to 46.31, p = 0.036). As the IFN system deficiency caused by neutralizing anti-IFN autoantibodies likely directly and indirectly exacerbates the likelihood of latent herpesvirus reactivations in critically ill patients, early diagnosis of anti-IFN IgG could be rapidly used to inform risk-group stratification and treatment options. Trial Registration: ClinicalTrials.gov Identifier: NCT04410263.
MeSH term(s)	Autoantibodies ; COVID-19 ; Critical Illness ; Cytomegalovirus Infections ; Herpes Simplex ; Humans ; Immunoglobulin G ; Interferon Type I ; SARS-CoV-2
Chemical Substances	Autoantibodies ; Immunoglobulin G ; Interferon Type I
Language	English
Publishing date	2022-07-05
Publishing country	United States
Document type	Clinical Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2126776-5
ISSN	1545-7885 ; 1544-9173
ISSN (online)	1545-7885
ISSN	1544-9173
DOI	10.1371/journal.pbio.3001709
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Article ; Online: Structure and dsRNA-binding activity of the Birnavirus Drosophila X Virus VP3 protein.

Ferrero, Diego S / Busnadiego, Idoia / Garriga, Damià / Guerra, Pablo / Martín, María Teresa / Kremer, Leonor / Usón, Isabel / Rodriguez, José Francisco / Verdaguer, Nuria

Journal of virology

2020 Volume 95, Issue 4

Abstract: The Birnavirus multifunctional protein VP3 plays an essential role coordinating the virus life cycle, interacting with the capsid protein VP2, with the RNA-dependent RNA polymerase VP1 and with the dsRNA genome. Furthermore, the role of this protein in ... ...

Abstract	The Birnavirus multifunctional protein VP3 plays an essential role coordinating the virus life cycle, interacting with the capsid protein VP2, with the RNA-dependent RNA polymerase VP1 and with the dsRNA genome. Furthermore, the role of this protein in controlling host cell responses triggered by dsRNA and preventing gene silencing has been recently demonstrated. Here we report the X-ray structure and dsRNA-binding activity of the N-terminal domain of Drosophila X virus (DXV) VP3. The domain folds in a bundle of three α-helices and arranges as a dimer, exposing to the surface a well-defined cluster of basic residues. Site directed mutagenesis combined with Electrophoretic Mobility Shift Assays (EMSA) and Surface Plasmon Resonance (SPR) revealed that this cluster, as well as a flexible and positively charged region linking the first and second globular domains of DXV VP3, are essential for dsRNA-binding. Also, RNA silencing studies performed in insect cell cultures confirmed the crucial role of this VP3 domain for the silencing suppression activity of the protein.
Language	English
Publishing date	2020-11-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.02166-20
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Article ; Online: Antiviral Activity of Type I, II, and III Interferons Counterbalances ACE2 Inducibility and Restricts SARS-CoV-2.

Busnadiego, Idoia / Fernbach, Sonja / Pohl, Marie O / Karakus, Umut / Huber, Michael / Trkola, Alexandra / Stertz, Silke / Hale, Benjamin G

mBio

2020 Volume 11, Issue 5

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), is a recently emerged respiratory coronavirus that has infected >23 million people worldwide with >800,000 deaths. Few COVID-19 therapeutics ... ...

Abstract	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), is a recently emerged respiratory coronavirus that has infected >23 million people worldwide with >800,000 deaths. Few COVID-19 therapeutics are available, and the basis for severe infections is poorly understood. Here, we investigated properties of type I (β), II (γ), and III (λ1) interferons (IFNs), potent immune cytokines that are normally produced during infection and that upregulate IFN-stimulated gene (ISG) effectors to limit virus replication. IFNs are already in clinical trials to treat COVID-19. However, recent studies highlight the potential for IFNs to enhance expression of host angiotensin-converting enzyme 2 (ACE2), suggesting that IFN therapy or natural coinfections could exacerbate COVID-19 by upregulating this critical virus entry receptor. Using a cell line model, we found that beta interferon (IFN-β) strongly upregulated expression of canonical antiviral ISGs, as well as ACE2 at the mRNA and cell surface protein levels. Strikingly, IFN-λ1 upregulated antiviral ISGs, but ACE2 mRNA was only marginally elevated and did not lead to detectably increased ACE2 protein at the cell surface. IFN-γ induced the weakest ISG response but clearly enhanced surface expression of ACE2. Importantly, all IFN types inhibited SARS-CoV-2 replication in a dose-dependent manner, and IFN-β and IFN-λ1 exhibited potent antiviral activity in primary human bronchial epithelial cells. Our data imply that type-specific mechanisms or kinetics shape IFN-enhanced ACE2 transcript and cell surface levels but that the antiviral action of IFNs against SARS-CoV-2 counterbalances any proviral effects of ACE2 induction. These insights should aid in evaluating the benefits of specific IFNs, particularly IFN-λ, as repurposed therapeutics.
MeSH term(s)	Aged ; Angiotensin-Converting Enzyme 2 ; Animals ; Antiviral Agents/pharmacology ; Betacoronavirus/immunology ; COVID-19 ; Cell Line ; Chlorocebus aethiops ; Coronavirus Infections/drug therapy ; Female ; Humans ; Immunotherapy/methods ; Interferon Type I/adverse effects ; Interferon Type I/pharmacology ; Interferon-gamma/adverse effects ; Interferon-gamma/pharmacology ; Interferons/adverse effects ; Interferons/pharmacology ; Pandemics ; Peptidyl-Dipeptidase A/genetics ; Peptidyl-Dipeptidase A/metabolism ; Pneumonia, Viral/drug therapy ; RNA, Messenger/biosynthesis ; RNA, Messenger/genetics ; Receptors, Virus/metabolism ; Respiratory Mucosa/cytology ; Respiratory Mucosa/virology ; SARS-CoV-2 ; Up-Regulation/drug effects ; Vero Cells ; Virus Replication/drug effects
Chemical Substances	Antiviral Agents ; Interferon Type I ; RNA, Messenger ; Receptors, Virus ; interferon type III ; Interferon-gamma (82115-62-6) ; Interferons (9008-11-1) ; Peptidyl-Dipeptidase A (EC 3.4.15.1) ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
Keywords	covid19
Language	English
Publishing date	2020-09-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2557172-2
ISSN	2150-7511 ; 2161-2129
ISSN (online)	2150-7511
ISSN	2161-2129
DOI	10.1128/mBio.01928-20
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Article ; Online: Combined computational and cellular screening identifies synergistic inhibition of SARS-CoV-2 by lenvatinib and remdesivir.

Pohl, Marie O / Busnadiego, Idoia / Marrafino, Francesco / Wiedmer, Lars / Hunziker, Annika / Fernbach, Sonja / Glas, Irina / Moroz-Omori, Elena V / Hale, Benjamin G / Caflisch, Amedeo / Stertz, Silke

The Journal of general virology

2021 Volume 102, Issue 7

Abstract: Rapid repurposing of existing drugs as new therapeutics for COVID-19 has been an important strategy in the management of disease severity during the ongoing SARS-CoV-2 pandemic. Here, we used high-throughput docking to screen 6000 compounds within the ... ...

Abstract	Rapid repurposing of existing drugs as new therapeutics for COVID-19 has been an important strategy in the management of disease severity during the ongoing SARS-CoV-2 pandemic. Here, we used high-throughput docking to screen 6000 compounds within the DrugBank library for their potential to bind and inhibit the SARS-CoV-2 3 CL main protease, a chymotrypsin-like enzyme that is essential for viral replication. For 19 candidate hits, parallel
MeSH term(s)	Adenosine Monophosphate/analogs & derivatives ; Adenosine Monophosphate/pharmacology ; Alanine/analogs & derivatives ; Alanine/pharmacology ; Animals ; Antiviral Agents/pharmacology ; COVID-19/enzymology ; COVID-19/virology ; Cells, Cultured ; Chymases/antagonists & inhibitors ; Drug Evaluation, Preclinical ; Humans ; Molecular Docking Simulation ; Phenylurea Compounds/pharmacology ; Protein Kinase Inhibitors/pharmacology ; Quinolines/pharmacology ; SARS-CoV-2/drug effects ; SARS-CoV-2/isolation & purification ; SARS-CoV-2/pathogenicity ; COVID-19 Drug Treatment
Chemical Substances	Antiviral Agents ; Phenylurea Compounds ; Protein Kinase Inhibitors ; Quinolines ; remdesivir (3QKI37EEHE) ; Adenosine Monophosphate (415SHH325A) ; Chymases (EC 3.4.21.39) ; lenvatinib (EE083865G2) ; Alanine (OF5P57N2ZX)
Language	English
Publishing date	2021-07-28
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	219316-4
ISSN	1465-2099 ; 0022-1317
ISSN (online)	1465-2099
ISSN	0022-1317
DOI	10.1099/jgv.0.001625
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Article ; Online: BRD9 is a druggable component of interferon-stimulated gene expression and antiviral activity.

Börold, Jacob / Eletto, Davide / Busnadiego, Idoia / Mair, Nina K / Moritz, Eva / Schiefer, Samira / Schmidt, Nora / Petric, Philipp P / Wong, W Wei-Lynn / Schwemmle, Martin / Hale, Benjamin G

EMBO reports

2021 Volume 22, Issue 10, Page(s) e52823

Abstract: Interferon (IFN) induction of IFN-stimulated genes (ISGs) creates a formidable protective antiviral state. However, loss of appropriate control mechanisms can result in constitutive pathogenic ISG upregulation. Here, we used genome-scale loss-of-function ...

Abstract	Interferon (IFN) induction of IFN-stimulated genes (ISGs) creates a formidable protective antiviral state. However, loss of appropriate control mechanisms can result in constitutive pathogenic ISG upregulation. Here, we used genome-scale loss-of-function screening to establish genes critical for IFN-induced transcription, identifying all expected members of the JAK-STAT signaling pathway and a previously unappreciated epigenetic reader, bromodomain-containing protein 9 (BRD9), the defining subunit of non-canonical BAF (ncBAF) chromatin-remodeling complexes. Genetic knockout or small-molecule-mediated degradation of BRD9 limits IFN-induced expression of a subset of ISGs in multiple cell types and prevents IFN from exerting full antiviral activity against several RNA and DNA viruses, including influenza virus, human immunodeficiency virus (HIV1), and herpes simplex virus (HSV1). Mechanistically, BRD9 acts at the level of transcription, and its IFN-triggered proximal association with the ISG transcriptional activator, STAT2, suggests a functional localization at selected ISG promoters. Furthermore, BRD9 relies on its intact acetyl-binding bromodomain and unique ncBAF scaffolding interaction with GLTSCR1/1L to promote IFN action. Given its druggability, BRD9 is an attractive target for dampening ISG expression under certain autoinflammatory conditions.
MeSH term(s)	Antiviral Agents/pharmacology ; Gene Expression ; Humans ; Interferons ; STAT2 Transcription Factor/genetics ; STAT2 Transcription Factor/metabolism ; Transcription Factors/genetics
Chemical Substances	Antiviral Agents ; BRD9 protein, human ; STAT2 Transcription Factor ; Transcription Factors ; Interferons (9008-11-1)
Language	English
Publishing date	2021-08-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2020896-0
ISSN	1469-3178 ; 1469-221X
ISSN (online)	1469-3178
ISSN	1469-221X
DOI	10.15252/embr.202152823
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Zs.A 5433: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: SARS-CoV-2 variants reveal features critical for replication in primary human cells.

Pohl, Marie O / Busnadiego, Idoia / Kufner, Verena / Glas, Irina / Karakus, Umut / Schmutz, Stefan / Zaheri, Maryam / Abela, Irene / Trkola, Alexandra / Huber, Michael / Stertz, Silke / Hale, Benjamin G

PLoS biology

2021 Volume 19, Issue 3, Page(s) e3001006

Abstract: Since entering the human population, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2; the causative agent of Coronavirus Disease 2019 [COVID-19]) has spread worldwide, causing >100 million infections and >2 million deaths. While large-scale ... ...

Abstract	Since entering the human population, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2; the causative agent of Coronavirus Disease 2019 [COVID-19]) has spread worldwide, causing >100 million infections and >2 million deaths. While large-scale sequencing efforts have identified numerous genetic variants in SARS-CoV-2 during its circulation, it remains largely unclear whether many of these changes impact adaptation, replication, or transmission of the virus. Here, we characterized 14 different low-passage replication-competent human SARS-CoV-2 isolates representing all major European clades observed during the first pandemic wave in early 2020. By integrating viral sequencing data from patient material, virus stocks, and passaging experiments, together with kinetic virus replication data from nonhuman Vero-CCL81 cells and primary differentiated human bronchial epithelial cells (BEpCs), we observed several SARS-CoV-2 features that associate with distinct phenotypes. Notably, naturally occurring variants in Orf3a (Q57H) and nsp2 (T85I) were associated with poor replication in Vero-CCL81 cells but not in BEpCs, while SARS-CoV-2 isolates expressing the Spike D614G variant generally exhibited enhanced replication abilities in BEpCs. Strikingly, low-passage Vero-derived stock preparation of 3 SARS-CoV-2 isolates selected for substitutions at positions 5/6 of E and were highly attenuated in BEpCs, revealing a key cell-specific function to this region. Rare isolate-specific deletions were also observed in the Spike furin cleavage site during Vero-CCL81 passage, but these were rapidly selected against in BEpCs, underscoring the importance of this site for SARS-CoV-2 replication in primary human cells. Overall, our study uncovers sequence features in SARS-CoV-2 variants that determine cell-specific replication and highlights the need to monitor SARS-CoV-2 stocks carefully when phenotyping newly emerging variants or potential variants of concern.
MeSH term(s)	Amino Acid Substitution ; Animals ; Base Sequence ; Bronchi/pathology ; COVID-19/diagnosis ; COVID-19/virology ; Cells, Cultured ; Chlorocebus aethiops ; Epithelial Cells/pathology ; Epithelial Cells/virology ; Furin/metabolism ; Host-Pathogen Interactions ; Humans ; SARS-CoV-2/isolation & purification ; SARS-CoV-2/physiology ; Vero Cells ; Virus Replication/physiology
Chemical Substances	Furin (EC 3.4.21.75)
Language	English
Publishing date	2021-03-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2126776-5
ISSN	1545-7885 ; 1544-9173
ISSN (online)	1545-7885
ISSN	1544-9173
DOI	10.1371/journal.pbio.3001006
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Article ; Online: SARS-CoV-2 variants reveal features critical for replication in primary human cells.

Marie O Pohl / Idoia Busnadiego / Verena Kufner / Irina Glas / Umut Karakus / Stefan Schmutz / Maryam Zaheri / Irene Abela / Alexandra Trkola / Michael Huber / Silke Stertz / Benjamin G Hale

PLoS Biology, Vol 19, Iss 3, p e

2021 Volume 3001006

Abstract	Since entering the human population, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2; the causative agent of Coronavirus Disease 2019 [COVID-19]) has spread worldwide, causing >100 million infections and >2 million deaths. While large-scale sequencing efforts have identified numerous genetic variants in SARS-CoV-2 during its circulation, it remains largely unclear whether many of these changes impact adaptation, replication, or transmission of the virus. Here, we characterized 14 different low-passage replication-competent human SARS-CoV-2 isolates representing all major European clades observed during the first pandemic wave in early 2020. By integrating viral sequencing data from patient material, virus stocks, and passaging experiments, together with kinetic virus replication data from nonhuman Vero-CCL81 cells and primary differentiated human bronchial epithelial cells (BEpCs), we observed several SARS-CoV-2 features that associate with distinct phenotypes. Notably, naturally occurring variants in Orf3a (Q57H) and nsp2 (T85I) were associated with poor replication in Vero-CCL81 cells but not in BEpCs, while SARS-CoV-2 isolates expressing the Spike D614G variant generally exhibited enhanced replication abilities in BEpCs. Strikingly, low-passage Vero-derived stock preparation of 3 SARS-CoV-2 isolates selected for substitutions at positions 5/6 of E and were highly attenuated in BEpCs, revealing a key cell-specific function to this region. Rare isolate-specific deletions were also observed in the Spike furin cleavage site during Vero-CCL81 passage, but these were rapidly selected against in BEpCs, underscoring the importance of this site for SARS-CoV-2 replication in primary human cells. Overall, our study uncovers sequence features in SARS-CoV-2 variants that determine cell-specific replication and highlights the need to monitor SARS-CoV-2 stocks carefully when phenotyping newly emerging variants or potential variants of concern.
Keywords	Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2021-03-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
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Article ; Online: An antiviral trap made of protein nanofibrils and iron oxyhydroxide nanoparticles.

Palika, Archana / Armanious, Antonius / Rahimi, Akram / Medaglia, Chiara / Gasbarri, Matteo / Handschin, Stephan / Rossi, Antonella / Pohl, Marie O / Busnadiego, Idoia / Gübeli, Christian / Anjanappa, Ravi B / Bolisetty, Sreenath / Peydayesh, Mohammad / Stertz, Silke / Hale, Benjamin G / Tapparel, Caroline / Stellacci, Francesco / Mezzenga, Raffaele

Nature nanotechnology

2021 Volume 16, Issue 8, Page(s) 918–925

Abstract: Minimizing the spread of viruses in the environment is the first defence line when fighting outbreaks and pandemics, but the current COVID-19 pandemic demonstrates how difficult this is on a global scale, particularly in a sustainable and environmentally ...

Abstract	Minimizing the spread of viruses in the environment is the first defence line when fighting outbreaks and pandemics, but the current COVID-19 pandemic demonstrates how difficult this is on a global scale, particularly in a sustainable and environmentally friendly way. Here we introduce and develop a sustainable and biodegradable antiviral filtration membrane composed of amyloid nanofibrils made from food-grade milk proteins and iron oxyhydroxide nanoparticles synthesized in situ from iron salts by simple pH tuning. Thus, all the membrane components are made of environmentally friendly, non-toxic and widely available materials. The membrane has outstanding efficacy against a broad range of viruses, which include enveloped, non-enveloped, airborne and waterborne viruses, such as SARS-CoV-2, H1N1 (the influenza A virus strain responsible for the swine flu pandemic in 2009) and enterovirus 71 (a non-enveloped virus resistant to harsh conditions, such as highly acidic pH), which highlights a possible role in fighting the current and future viral outbreaks and pandemics.
MeSH term(s)	Amyloid/chemistry ; Amyloid/pharmacology ; Antiviral Agents/chemistry ; Antiviral Agents/pharmacology ; Ferric Compounds/chemistry ; Ferric Compounds/pharmacology ; Humans ; Lactoglobulins/chemistry ; Micropore Filters/virology ; Nanoparticles/chemistry ; Virus Inactivation/drug effects ; Viruses/classification ; Viruses/drug effects ; Viruses/isolation & purification ; Water Purification
Chemical Substances	Amyloid ; Antiviral Agents ; Ferric Compounds ; Lactoglobulins ; ferric hydroxide (2UA751211N)
Language	English
Publishing date	2021-06-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2254964-X
ISSN	1748-3395 ; 1748-3387
ISSN (online)	1748-3395
ISSN	1748-3387
DOI	10.1038/s41565-021-00920-5
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