المؤلفون: Simón-Fuentes, Miriam, Ríos, Israel, Herrero, Cristina, Lasala, Fátima, Labiod, Nuria, Luczkowiak, Joanna, Roy-Vallejo, Emilia, Fernández de Córdoba-Oñate, Sara, Delgado-Wicke, Pablo, Bustos, Matilde, Fernández-Ruiz, Elena, Colmenares, María, Puig-Kröger, Amaya, Delgado, Rafael, Vega Palacios, Miguel A., Corbí, Angel L., Domínguez-Soto, Ángeles

المساهمون: Ministerio de Ciencia e Innovación (España), Fundación BBVA, Comunidad de Madrid, Instituto de Salud Carlos III, Red de Enfermedades Inflamatorias (España), European Commission, Fundación la Caixa, Consejo Superior de Investigaciones Científicas (España), Ministerio de Economía y Competitividad (España), Simón-Fuentes, Miriam, Lasala, Fátima, Labiod, Nuria, Luczkowiak, Joanna, Roy-Vallejo, Emilia, Fernández de Córdoba-Oñate, Sara, Delgado-Wicke, Pablo, Bustos, Matilde, Fernández-Ruiz, Elena, Colmenares, María, Puig-Kröger, Amaya, Delgado, Rafael, Vega Palacios, Miguel A., Corbí, Angel L., Domínguez-Soto, Ángeles

مصطلحات موضوعية: COVID-19, Cellular immune response, Immunology, Macrophages, Molecular pathology

الوصف: 22 p.-6 fig.1 graph. abst. ; Monocyte-derived macrophages, the major source of pathogenic macrophages in COVID-19, are oppositely instructed by macrophage CSF (M-CSF) or granulocyte macrophage CSF (GM-CSF), which promote the generation of antiinflammatory/immunosuppressive MAFB+ (M-MØ) or proinflammatory macrophages (GM-MØ), respectively. The transcriptional profile of prevailing macrophage subsets in severe COVID-19 led us to hypothesize that MAFB shapes the transcriptome of pulmonary macrophages driving severe COVID-19 pathogenesis. We have now assessed the role of MAFB in the response of monocyte-derived macrophages to SARS-CoV-2 through genetic and pharmacological approaches, and we demonstrate that MAFB regulated the expression of the genes that define pulmonary pathogenic macrophages in severe COVID-19. Indeed, SARS-CoV-2 potentiated the expression of MAFB and MAFB-regulated genes in M-MØ and GM-MØ, where MAFB upregulated the expression of profibrotic and neutrophil-attracting factors. Thus, MAFB determines the transcriptome and functions of the monocyte-derived macrophage subsets that underlie pulmonary pathogenesis in severe COVID-19 and controls the expression of potentially useful biomarkers for COVID-19 severity. ; This work was supported by grant PID2020-114323RB-I00 from Ministerio de Ciencia e Innovación to ALC; “Ayudas FUNDACIÓN BBVA a equipos de investigación científica SARS-CoV-2 y COVID-19” to MAV and ALC; Dirección General de Innovación e Investigación Tecnológica de la Comunidad de Madrid (RETARACOVID, P2022/BMD-7274) to ALC, APK, EFR, and RD; Instituto de Salud Carlos III (grant PI20/00316 to APK, grant PI2100989 to RD, grant PI22/00428 to EFR); Red de Enfermedades Inflamatorias (RICORS RD21/0002/0034) from Instituto de Salud Carlos III and cofinanced by the European Regional Development Fund “A way to achieve Europe” (ERDF) and PRTR to APK; European Commission Horizon 2020 FP (Project VIRUSCAN FETPROACT-2016: ID 731868); Horizon Europe FP (Project EPIC-CROWN-2 ID: 101046084); and Fundación ...

العلاقة: #PLACEHOLDER_PARENT_METADATA_VALUE#; info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-114323RB-I00/ES/POLARIZACION Y RE-PROGRAMACION DE MACROFAGOS HUMANOS POR SEROTONINA: PAPEL DEL ARYL HYDROCARBON RECEPTOR (AHR) Y LOS FACTORES LXR Y SREBP/; S2022/BMD-7274_RETAR-A-COVID-CM; info:eu-repo/grantAgreement/EC/H2020/731868; Publisher's version; https://doi.org/10.1172/jci.insight.172862Test; Sí; JCI Insight 8 (24) e172862 (2023); http://hdl.handle.net/10261/352478Test

الإتاحة: https://doi.org/10.1172/jci.insight.172862Test
http://hdl.handle.net/10261/352478Test

المؤلفون: Simón-Fuentes, Miriam, Herrero, Cristina, Acero-Riaguas, Lucía, Nieto, Concha, Lasala, Fátima, Labiod, Nuria, Luczkowiak, Joanna, Alonso, Bárbara, Delgado, Rafael, Colmenares, María, Corbí, Angel L., Domínguez-Soto, Ángeles

المساهمون: Ministerio de Ciencia e Innovación (España), Fundación BBVA, Fundació La Marató de TV3, Instituto de Salud Carlos III, European Commission, Fundación "la Caixa", Red de Investigación en Enfermedades Reumáticas (España), Consejo Superior de Investigaciones Científicas (España), Simón-Fuentes, Miriam, Acero-Riaguas, Lucía, Nieto, Concha, Lasala, Fátima, Labiod, Nuria, Luczkowiak, Joanna, Alonso, Bárbara, Delgado, Rafael, Colmenares, María b, Corbí, Angel L., Domínguez-Soto, Ángeles

الوصف: 23 p.-5 fig. ; Toll-like receptor 7 (TLR7) is an endosomal Pathogen-Associated Molecular Pattern (PAMP) receptor that senses single-stranded RNA (ssRNA) and whose engagement results in the production of type I IFN and pro-inflammatory cytokines upon viral exposure. Recent genetic studies have established that a dysfunctional TLR7-initiated signaling is directly linked to the development of inflammatory responses. We present evidences that TLR7 is preferentially expressed by monocyte-derived macrophages generated in the presence of M-CSF (M-MØ). We now show that TLR7 activation in M-MØ triggers a weak MAPK, NFκB and STAT1 activation and results in low production of type I IFN. Of note, TLR7 engagement re-programs MAFB+ M-MØ towards a pro-inflammatory transcriptional profile characterized by the expression of neutrophil-attracting chemokines (CXCL1-3, CXCL5, CXCL8), whose expression is dependent on the transcription factors MAFB and AhR. Moreover, TLR7-activated M-MØ display enhanced pro-inflammatory responses and a stronger production of neutrophil-attracting chemokines upon secondary stimulation. As aberrant TLR7 signaling and enhanced pulmonary neutrophil/lymphocyte ratio associate with impaired resolution of virus-induced inflammatory responses, these results suggest that targeting macrophage TLR7 might be a therapeutic strategy for viral infections where monocyte-derived macrophages exhibit a pathogenic role. ; This work was supported by Grant PID2020-114323RB-I00 from Ministerio de Ciencia e Innovación, “Ayudas FUNDACIÓN BBVA a equipos de investigación científica SARS-CoV-2 y COVID-19” and Grant 201619.31 from Fundació La Marató/TV3 to ALC, grants from the Instituto de Investigación Carlos III, ISCIII,(PI2100989), European Commission Horizon 2020 FP (Project VIRUSCAN FETPROACT-2016: ID 731868), Horizon Europe FP (Project EPIC-CROWN-2 ID: 101046084) and Fundación Caixa-Health Research (Project StopEbola HR18-00469) to RD, and Red de Investigación en Enfermedades Reumáticas (RIER, RD16/0012/0007), and ...

العلاقة: #PLACEHOLDER_PARENT_METADATA_VALUE#; info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-114323RB-I00/ES/POLARIZACION Y RE-PROGRAMACION DE MACROFAGOS HUMANOS POR SEROTONINA: PAPEL DEL ARYL HYDROCARBON RECEPTOR (AHR) Y LOS FACTORES LXR Y SREBP/; info:eu-repo/grantAgreement/EC/H2020/731868; Postprint; https://doi.org/10.1159/000530249Test; Sí; Journal of Innate Immunity (2023); http://hdl.handle.net/10261/306731Test

الإتاحة: https://doi.org/10.1159/000530249Test
http://hdl.handle.net/10261/306731Test

المؤلفون: García-Rubia, Alfonso, Lasala, Fátima, Ginex, Tiziana, Morales-Tenorio, Marcos, Olal, Catherine, Heung, Michelle, Oquist Phillips, Mayra Paola, Galindo, Inmaculada, Cuesta-Geijo,Miguel Angel, Casasnovas, José María, Campillo, Nuria E., Canales, Ángeles, Alonso, Covadonga, Martínez, Ana, Muñoz-Fontela, César, Delgado, Rafael, Gil, Carmen

المساهمون: Fundación "la Caixa", Agencia Estatal de Investigación (España), Instituto de Salud Carlos III, European Commission, Consejo Superior de Investigaciones Científicas (España), Ministerio de Ciencia e Innovación (España), García-Rubia, Alfonso, Lasala, Fátima, Ginex, Tiziana, Morales-Tenorio, Marcos, Oquist Phillips, Mayra Paola, Galindo, Inmaculada, Cuesta-Geijo,Miguel Angel, Casasnovas, José María, Campillo, Nuria E., Canales, Ángeles, Alonso, Covadonga, Martínez, Ana, Muñoz-Fontela, César, Delgado, Rafael, Gil, Carmen

الوصف: 19 p.-6 fig.-7 tab.-1 graph. abst. ; Ebola virus (EBOV) is a single-strand RNA virus belonging to the Filoviridae family, which has been associated to most Ebola virus disease outbreaks to date, including the West African and the North Kivu epidemics between 2013 and 2022. This unprecedented health emergency prompted the search for effective medical countermeasures. Following up on the carbazole hit identified in our previous studies, we synthetized a new series of compounds, which demonstrated to prevent EBOV infection in cells by acting as virus entry inhibitors. The in vitro inhibitory activity was evaluated through the screening against surrogate models based on viral pseudotypes and further confirmed using replicative EBOV. Docking and molecular dynamics simulations joined to saturation transfer difference–nuclear magnetic resonance (STD–NMR) and mutagenesis experiments to elucidate the biological target of the most potent compounds. Finally, in vitro metabolic stability and in vivo pharmacokinetic studies were performed to confirm their therapeutic potential. ; The project leading to these results has received funding from “la Caixa” Foundation under the project code LCF/PR/HR19/52160012. This research was partially supported through ERA-NET-2021-862605. Cofounded by AEI, Spain (PCI2021-121939 (C.A.), PID2019-105237GB-I00 (A.C.), PID2021-122825OB (C.A.), and PID2021-122223OB-I00 (C.G.)), Instituto de Salud Carlos III (CIBERINFEC and FIS PI2100989), and the European Commission Horizon 2020 Framework Programme (Project VIRUSCAN FETPROACT-2016: 731868 and Project EPIC-CROWN-2 ID: 101046084). This research work was also funded by the European Commission–NextGenerationEU (Regulation EU 2020/2094), through CSIC’s Global Health Platform (PTI Salud Global). M.M.-T holds a predoctoral FPU grant (FPU18/03493) from MICINN ; Peer reviewed

العلاقة: #PLACEHOLDER_PARENT_METADATA_VALUE#; info:eu-repo/grantAgreement/EC/H2020/862605; info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PCI2021-121939/ES/DECODING A VIRUS ACHILLES HEEL: THE AFRICAN SWINE FEVER VIRUS INTERACTOME/; info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-105237GB-I00/ES/NUEVAS METODOLOGIAS DE RMN PARA ESTUDIAR N-GLICANOS Y GLICOPROTEINAS/; info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2021-122825OB/ES/Factores moleculares de restricción en la vía endocítica e interferencia global de los sistemas celulares por el virus de la Peste porcina africana/; info:eu-repo/grantAgreement/EC/H2020/731868; Publisher's version; https://doi.org/10.1021/acs.jmedchem.2c01785Test; Sí; Journal of Medicinal Chemistry (2023); http://hdl.handle.net/10261/305819Test

الإتاحة: https://doi.org/10.1021/acs.jmedchem.2c01785Test
http://hdl.handle.net/10261/305819Test

المؤلفون: Luczkowiak, Joanna, Rivas, Gonzalo, Labiod, Nuria, Lasala, Fátima, Rolo, Marta, Lora-Tamayo Morillo-Velarde, Jaime, Mancheno Losa, Mikel, Rial Crestelo, David, Pérez Rivilla, Alfredo, Folgueira López, María Dolores, Delgado Vázquez, Rafael

مصطلحات موضوعية: avidity, COVID‐19, neutralizing antibodies, Omicron, SARS‐CoV‐2, vaccines, variants of concern, Inmunología, 2412 Inmunología

الوصف: CRUE-CSIC (Acuerdos Transformativos 2022) ; We have measured the humoral response to messenger RNA (mRNA) vaccines in COVID-19 naïve and convalescent individuals. Third doses of mRNA COVID-19 vaccines induced a significant increase in potency and breadth of neutralization against SARS-CoV-2 variants of concern (VoC) including Omicron subvariants BA.1, BA.2, and BA.2.12.1, that were cross-neutralized at comparable levels and less for BA.4/5. This booster effect was especially important in naïve individuals that only after the third dose achieved a level that was comparable with that of vaccinated COVID-19 convalescents except for BA.4/5. Avidity of RBD-binding antibodies was also significantly increased in naïve individuals after the third dose, indicating an association between affinity maturation and cross neutralization of VoC. These results suggest that at least three antigenic stimuli by infection or vaccination with ancestral SARS-CoV-2 sequences are required to induce high avidity cross-neutralizing antibodies. Nevertheless, the circulation of new subvariants such as BA.4/5 with partial resistance to neutralization will have to be closely monitored and eventually consider for future vaccine developments. ; Depto. de Medicina ; Fac. de Medicina ; TRUE ; Union Europea. Horizonte Europa ; Unión Europea. Horizonte 2020 ; Instituto de Salud Carlos III (ISCIII) ; Fundación Caixa‐Health Research ; pub

وصف الملف: application/pdf

العلاقة: EPIC-CROWN-2 (101046084); VIRUSCAN (731868); FIS PI1801007 and PI2100989; Project StopEbola HR18‐ 00469; https://doi.org/10.1002/jmv.28268Test; https://hdl.handle.net/20.500.14352/72699Test

الإتاحة: https://doi.org/20.500.14352/72699Test
https://doi.org/10.1002/jmv.28268Test
https://hdl.handle.net/20.500.14352/72699Test

المؤلفون: Rivas, Gonzalo, Labiod, Nuria, Luczkowiak, Joanna, Lasala, Fátima, Rolo, Marta, Mancheño‐Losa, Mikel, Rial‐Crestelo, David, Lora‐Tamayo, Jaime, Pérez‐Rivilla, Alfredo, Folgueira, María Dolores, Delgado, Rafael

المصدر: Journal of Medical Virology ; volume 95, issue 11 ; ISSN 0146-6615 1096-9071

الوصف: Currently, the majority of the population has been vaccinated against COVID‐19 and/or has experienced SARS‐CoV‐2 infection either before or after vaccination. The immunological response to repeated episodes of infections is not completely clear. We measured SARS‐CoV‐2 specific neutralization titers by a pseudovirus assay after BA.1 infection and RBD‐specific immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin M (IgM) in a cohort of COVID‐19 uninfected and triple vaccinated individuals (breakthrough infection group, BTI) as compared with those previously infected by SARS‐CoV‐2 (reinfection group, REI) who underwent identical vaccination schedule. SARS‐CoV‐2 specific neutralizing response after BA.1 infection was significantly higher in the BTI group as compared with the REI. Furthermore, neutralization titers in REI were not significant different from convalescent non reinfected controls. RBD‐specific IgG and IgA, but not IgM, were also significantly higher in BTI as compared with REI. Our results show that the first episode of SARS‐CoV‐2 infection induces a significant increase in neutralizing titers in triple vaccinated individuals and that previous SARS‐CoV‐2 infection compromise significantly the neutralization response induced by reinfection, even by divergent SARS‐CoV‐2 variants and at least up to 2 years postinfection, suggesting a fundamental limitation in inducing effective booster through the intranasal route in previously infected individuals.

الإتاحة: https://doi.org/10.1002/jmv.29225Test

المؤلفون: Patino‐Alonso, Jennifer, Cabrera‐González, Justo, Merino, Javier, Nieto‐Ortiz, Gema, Lasala, Fátima, Katati, Jouma, da Cruz, Carlos H. Bezerra, Monnappa, Ajay K., Mateos‐Gil, Pablo, Canales, Ángeles, López‐Montero, Iván, Illescas, Beatriz M., Delgado, Rafael, Martín, Nazario

المساهمون: Comunidad de Madrid, Agencia Estatal de Investigación, Spanish National Plan for Scientific and Technical Research and Innovation, European Regional Development Fund

المصدر: Small ; ISSN 1613-6810 1613-6829

الوصف: Since WHO has declared the COVID‐19 outbreak a global pandemic, nearly seven million deaths have been reported. This efficient spread of Severe Acute Respiratory Syndrome Coronavirus‐2 (SARS‐CoV‐2) is facilitated by the ability of the spike glycoprotein to bind multiple cell membrane receptors. Although ACE2 is identified as the main receptor for SARS‐CoV‐2, other receptors could play a role in viral entry. Among others, C‐type lectins such as DC‐SIGN are identified as efficient trans‐receptor for SARS‐CoV‐2 infection, so the use of glycomimetics to inhibit the infection through the DC‐SIGN blockade is an encouraging approach. In this regard, multivalent nanostructures based on glycosylated [60]fullerenes linked to a central porphyrin scaffold have been designed and tested against DC‐SIGN‐mediated SARS‐CoV‐2 infection. First results show an outstanding inhibition of the trans‐infection up to 90%. In addition, a deeper understanding of nanostructure‐receptor binding is achieved through microscopy techniques, high‐resolution NMR experiments, Quartz Crystal Microbalance experiments, and molecular dynamic simulations.

الإتاحة: https://doi.org/10.1002/smll.202307045Test

المؤلفون: Labiod, Nuria, Luczkowiak, Joanna, Tapia, María M., Lasala, Fátima, Delgado, Rafael

المصدر: Frontiers in Cellular and Infection Microbiology ; volume 13 ; ISSN 2235-2988

مصطلحات موضوعية: Infectious Diseases, Microbiology (medical), Immunology, Microbiology

الوصف: DC-SIGN is a C-type lectin expressed in myeloid cells such as immature dendritic cells and macrophages. Through glycan recognition in viral envelope glycoproteins, DC-SIGN has been shown to act as a receptor for a number of viral agents such as HIV, Ebola virus, SARS-CoV, and SARS-CoV-2. Using a system of Vesicular Stomatitis Virus pseudotyped with MERS-CoV spike protein, here, we show that DC-SIGN is partially responsible for MERS-CoV infection of dendritic cells and that DC-SIGN efficiently mediates trans-infection of MERS-CoV from dendritic cells to susceptible cells, indicating a potential role of DC-SIGN in MERS-CoV dissemination and pathogenesis.

الإتاحة: https://doi.org/10.3389/fcimb.2023.1177270Test

المؤلفون: Patino‐Alonso, Jennifer, Cabrera‐González, Justo, Merino, Javier, Nieto‐Ortiz, Gema, Lasala, Fátima, Katati, Jouma, da Cruz, Carlos H. Bezerra, Monnappa, Ajay K., Mateos‐Gil, Pablo, Canales, Ángeles, López‐Montero, Iván, Illescas, Beatriz M., Delgado, Rafael, Martín, Nazario

المصدر: Small; 5/18/2024, Vol. 20 Issue 19, p1-11, 11p

المؤلفون: Cuesta-Geijo, Miguel Ángel, García-Dorival, Isabel, Puerto, Ana del, Urquiza, Jesús, Galindo, Immaculada, Barrado-Gil, Lucía, Lasala, Fátima, Cayuela, Ana, Sorzano, Carlos Óscar S., Gil, Carmen, Delgado, Rafael, Alonso, Covandoga

المساهمون: La Caixa, Ministerio de Ciencia e Innovación (España), Instituto de Salud Carlos III, European Commission, Cuesta-Geijo, Miguel Ángel, García-Dorival, Isabel, Puerto, Ana del, Urquiza, Jesús, Galindo, Immaculada, Barrado-Gil, Lucía, Lasala, Fátima, Sorzano, Carlos Óscar S., Gil, Carmen, Delgado, Rafael, Alonso, Covandoga

الوصف: 28 p.-7 fig.-- Departamento de Biotecnología. ; African swine fever virus (ASFV) infectious cycle starts with the viral adsorption and entry into the host cell. Then, the virus is internalized via clathrin/dynamin mediated endocytosis and macropinocytosis. Similar to other viruses, ASF virion is then internalized and incorporated into the endocytic pathway. While the endosomal maturation entails luminal acidification, the decrease in pH acts on the multilayer structure of the virion dissolving the outer capsid. Upon decapsidation, the inner viral membrane is exposed to interact with the limiting membrane of the late endosome for fusion. Viral fusion is then necessary for the egress of incoming virions from endosomes into the cytoplasm, however this remains an intriguing and yet essential process for infection, specifically for the egress of viral nucleic acid into the cytoplasm for replication. ASFV proteins E248R and E199L, located at the exposed inner viral membrane, might be implicated in the fusion step. An interaction between these viral proteins and cellular endosomal proteins such as the Niemann-Pick C type 1 (NPC1) and lysosomal membrane proteins (Lamp-1 and -2) was shown. Furthermore, the silencing of these proteins impaired ASFV infection. It was also observed that NPC1 knock-out cells using CRISPR jeopardized ASFV infection and that the progression and endosomal exit of viral cores was arrested within endosomes at viral entry. These results suggest that the interactions of ASFV proteins with some endosomal proteins might be important for the membrane fusion step. In addition to this, reductions on ASFV infectivity and replication in NPC1 KO cells were accompanied by fewer and smaller viral factories. Our findings pave the way to understanding the role of proteins of the endosomal membrane in ASFV infection. ; This research was partially supported through the following awards: “La Caixa” Banking Foundation award number LCF/PR/HR19/52160012, Spain, https://fundacionlacaixa.org/enTest/ to CA and RD, Spanish ...

العلاقة: #PLACEHOLDER_PARENT_METADATA_VALUE#; info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-097305-R-I00/ES/CARACTERIZACION DE DETERMINANTES GENETICOS RELEVANTES PARA EL DESARROLLO DE UNA VACUNA FRENTE AL VIRUS DE LA PESTE PORCINA AFRICANA/; info:eu-repo/grantAgreement/EC/H2020/862605; info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PCI2021-121939/ES/DECODING A VIRUS ACHILLES HEEL: THE AFRICAN SWINE FEVER VIRUS INTERACTOME/; info:eu-repo/grantAgreement/EC/H2020/731868; Publisher's version; https://doi.org/10.1371/journal.ppat.1009784Test; Sí; PLoS Pathogens 18 (1) e1009784 (2022); http://hdl.handle.net/10261/260885Test; http://dx.doi.org/10.13039/501100004837Test; http://dx.doi.org/10.13039/501100000780Test; http://dx.doi.org/10.13039/501100004587Test

الإتاحة: https://doi.org/10.1371/journal.ppat.1009784Test
https://doi.org/10.13039/501100004837Test
https://doi.org/10.13039/501100000780Test
https://doi.org/10.13039/501100004587Test
http://hdl.handle.net/10261/260885Test

المؤلفون: Patino-Alonso, Jennifer, Cabrera-González, Justo, Merino, Javier, Nieto-Ortiz, Gema, Lasala, Fátima, Katati, Jouma, da Cruz, Carlos H Bezerra, Monnappa, Ajay K, Mateos-Gil, Pablo, Canales, Ángeles, López-Montero, Iván, Illescas, Beatriz M, Delgado, Rafael, Martín, Nazario

المصدر: Small ; ISSN:1613-6829 ; Volume:20 ; Issue:19

الوصف: Since WHO has declared the COVID-19 outbreak a global pandemic, nearly seven million deaths have been reported. This efficient spread of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is facilitated by the ability of the spike glycoprotein to bind multiple cell membrane receptors. Although ACE2 is identified as the main receptor for SARS-CoV-2, other receptors could play a role in viral entry. Among others, C-type lectins such as DC-SIGN are identified as efficient trans-receptor for SARS-CoV-2 infection, so the use of glycomimetics to inhibit the infection through the DC-SIGN blockade is an encouraging approach. In this regard, multivalent nanostructures based on glycosylated [60]fullerenes linked to a central porphyrin scaffold have been designed and tested against DC-SIGN-mediated SARS-CoV-2 infection. First results show an outstanding inhibition of the trans-infection up to 90%. In addition, a deeper understanding of nanostructure-receptor binding is achieved through microscopy techniques, high-resolution NMR experiments, Quartz Crystal Microbalance experiments, and molecular dynamic simulations.

العلاقة: https://doi.org/10.1002/smll.202307045Test; https://pubmed.ncbi.nlm.nih.gov/38100142Test

الإتاحة: https://doi.org/10.1002/smll.202307045Test
https://pubmed.ncbi.nlm.nih.gov/38100142Test