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Nuria Izquierdo-Useros
IrsiCaixa AIDS Research Institute, Germans Trias I Pujol Research Institute (IGTP), Can Ruti Campus, 08916 Badalona, Spain

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Journal article
Published: 25 August 2021 in Viruses
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To date, no evidence supports the fact that animals play a role in the epidemiology of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the coronavirus infectious disease 2019 (COVID-19). However, several animal species are naturally susceptible to SARS-CoV-2 infection. Besides pets (cats, dogs, Syrian hamsters, and ferrets) and farm animals (minks), different zoo animal species have tested positive for SARS-CoV-2 (large felids and non-human primates). After the summer of 2020, a second wave of SARS-CoV-2 infection occurred in Barcelona (Spain), reaching a peak of positive cases in November. During that period, four lions (Panthera leo) at the Barcelona Zoo and three caretakers developed respiratory signs and tested positive for the SARS-CoV-2 antigen. Lion infection was monitored for several weeks and nasal, fecal, saliva, and blood samples were taken at different time-points. SARS-CoV-2 RNA was detected in nasal samples from all studied lions and the viral RNA was detected up to two weeks after the initial viral positive test in three out of four animals. The SARS-CoV-2 genome was also detected in the feces of animals at different times. Virus isolation was successful only from respiratory samples of two lions at an early time-point. The four animals developed neutralizing antibodies after the infection that were detectable four months after the initial diagnosis. The partial SARS-CoV-2 genome sequence from one animal caretaker was identical to the sequences obtained from lions. Chronology of the events, the viral dynamics, and the genomic data support human-to-lion transmission as the origin of infection.

ACS Style

Hugo Fernández-Bellon; Jordi Rodon; Leira Fernández-Bastit; Vanessa Almagro; Pilar Padilla-Solé; Cristina Lorca-Oró; Rosa Valle; Núria Roca; Santina Grazioli; Tiziana Trogu; Albert Bensaid; Jorge Carrillo; Nuria Izquierdo-Useros; Julià Blanco; Mariona Parera; Marc Noguera-Julián; Bonaventura Clotet; Ana Moreno; Joaquim Segalés; Júlia Vergara-Alert. Monitoring Natural SARS-CoV-2 Infection in Lions (Panthera leo) at the Barcelona Zoo: Viral Dynamics and Host Responses. Viruses 2021, 13, 1683 .

AMA Style

Hugo Fernández-Bellon, Jordi Rodon, Leira Fernández-Bastit, Vanessa Almagro, Pilar Padilla-Solé, Cristina Lorca-Oró, Rosa Valle, Núria Roca, Santina Grazioli, Tiziana Trogu, Albert Bensaid, Jorge Carrillo, Nuria Izquierdo-Useros, Julià Blanco, Mariona Parera, Marc Noguera-Julián, Bonaventura Clotet, Ana Moreno, Joaquim Segalés, Júlia Vergara-Alert. Monitoring Natural SARS-CoV-2 Infection in Lions (Panthera leo) at the Barcelona Zoo: Viral Dynamics and Host Responses. Viruses. 2021; 13 (9):1683.

Chicago/Turabian Style

Hugo Fernández-Bellon; Jordi Rodon; Leira Fernández-Bastit; Vanessa Almagro; Pilar Padilla-Solé; Cristina Lorca-Oró; Rosa Valle; Núria Roca; Santina Grazioli; Tiziana Trogu; Albert Bensaid; Jorge Carrillo; Nuria Izquierdo-Useros; Julià Blanco; Mariona Parera; Marc Noguera-Julián; Bonaventura Clotet; Ana Moreno; Joaquim Segalés; Júlia Vergara-Alert. 2021. "Monitoring Natural SARS-CoV-2 Infection in Lions (Panthera leo) at the Barcelona Zoo: Viral Dynamics and Host Responses." Viruses 13, no. 9: 1683.

Article
Published: 13 August 2021
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Background Understanding the determinants of long-term immune responses to SARS-CoV-2 and the concurrent impact of vaccination and emerging variants of concern will guide optimal strategies to achieve global protection against the COVID-19 pandemic. Methods A prospective cohort of 332 COVID-19 patients was followed beyond one year. Plasma neutralizing activity was evaluated using HIV-based reporter pseudoviruses expressing different SARS-CoV-2 spikes and was longitudinally analyzed using mixed-effects models. Findings Long-term neutralizing activity was stable beyond one year after infection in mild/asymptomatic and hospitalized participants. However, longitudinal models suggest that hospitalized individuals generate both short- and long-lived memory B cells, while outpatient responses were dominated by long-lived B cells. In both groups, vaccination boosted responses to natural infection, although viral variants, mainly B.1.351, reduced the efficacy of neutralization. Importantly, despite showing higher neutralization titers, hospitalized patients showed lower cross-neutralization of B.1.351 variant compared to outpatients. Multivariate analysis identified severity of primary infection as the factor that independently determines both the magnitude and the inferior cross-neutralization activity of long-term neutralizing responses. Conclusions Neutralizing response induced by SARS-CoV-2 is heterogeneous in magnitude but stable beyond one year after infection. Vaccination boosts these long-lasting natural neutralizing responses, counteracting the significant resistance to neutralization of new viral variants. Severity of primary infection determines higher magnitude but poorer quality of long-term neutralizing responses.

ACS Style

Edwards Pradenas; Benjamin Trinité; Víctor Urrea; Silvia Marfil; Ferran Tarrés-Freixas; Raquel Ortiz; Carla Rovirosa; Jordi Rodon; Júlia Vergara-Alert; Joaquim Segalés; Victor Guallar; Alfonso Valencia; Nuria Izquierdo-Useros; Marc Noguera-Julian; Jorge Carrillo; Roger Paredes; Lourdes Mateu; Anna Chamorro; Ruth Toledo; Marta Massanella; Bonaventura Clotet; Julià Blanco. Clinical course impacts early kinetics and long-term magnitude and amplitude of SARS-CoV-2 neutralizing antibodies beyond one year after infection. 2021, 1 .

AMA Style

Edwards Pradenas, Benjamin Trinité, Víctor Urrea, Silvia Marfil, Ferran Tarrés-Freixas, Raquel Ortiz, Carla Rovirosa, Jordi Rodon, Júlia Vergara-Alert, Joaquim Segalés, Victor Guallar, Alfonso Valencia, Nuria Izquierdo-Useros, Marc Noguera-Julian, Jorge Carrillo, Roger Paredes, Lourdes Mateu, Anna Chamorro, Ruth Toledo, Marta Massanella, Bonaventura Clotet, Julià Blanco. Clinical course impacts early kinetics and long-term magnitude and amplitude of SARS-CoV-2 neutralizing antibodies beyond one year after infection. . 2021; ():1.

Chicago/Turabian Style

Edwards Pradenas; Benjamin Trinité; Víctor Urrea; Silvia Marfil; Ferran Tarrés-Freixas; Raquel Ortiz; Carla Rovirosa; Jordi Rodon; Júlia Vergara-Alert; Joaquim Segalés; Victor Guallar; Alfonso Valencia; Nuria Izquierdo-Useros; Marc Noguera-Julian; Jorge Carrillo; Roger Paredes; Lourdes Mateu; Anna Chamorro; Ruth Toledo; Marta Massanella; Bonaventura Clotet; Julià Blanco. 2021. "Clinical course impacts early kinetics and long-term magnitude and amplitude of SARS-CoV-2 neutralizing antibodies beyond one year after infection." , no. : 1.

Article
Published: 03 August 2021
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SARS-CoV-2 variants display enhanced transmissibility and/or immune evasion and can be generated in humans or animals, like minks, thus generating new reservoirs. The continuous surveillance of animal susceptibility to new variants is necessary to predict pandemic evolution. In this study we demonstrate that, compared to the B.1 SARS-CoV-2 variant, K18-hACE2 transgenic mice challenged with the B.1.351 variant displayed a faster progression of infection. Furthermore, we also report that B.1.351 can establish infection in wildtype mice, while B.1 cannot. B.1.351-challenged wildtype mice showed a milder infection than transgenic mice, confirmed by detectable viral loads in oropharyngeal swabs and tissues, lung pathology, immunohistochemistry and serology. In silico models supported these findings by demonstrating that the Spike mutations in B.1.351 resulted in increased affinity for both human and murine ACE2 receptors. Overall, this study highlights the plasticity of SARS-CoV-2 animal susceptibility landscape, which may contribute to viral persistence and expansion.

ACS Style

Ferran Tarrés-Freixas; Benjamin Trinité; Anna Pons-Grífols; Miguel Romero-Durana; Eva Riveira-Muñoz; Carlos Ávila-Nieto; Mónica Pérez; Edurne Garcia-Vidal; Daniel Pérez-Zsolt; Jordana Muñoz-Basagoiti; Dàlia Raïch-Regué; Nuria Izquierdo-Useros; Ignacio Blanco; Marc Noguera-Julián; Victor Guallar; Rosalba Lepore; Alfonso Valencia; Júlia Vergara-Alert; Bonaventura Clotet; Ester Ballana; Jorge Carrillo; Joaquim Segalés; Julià Blanco. SARS-CoV-2 B.1.351 (beta) variant shows enhanced infectivity in K18-hACE2 transgenic mice and expanded tropism to wildtype mice compared to B.1 variant. 2021, 1 .

AMA Style

Ferran Tarrés-Freixas, Benjamin Trinité, Anna Pons-Grífols, Miguel Romero-Durana, Eva Riveira-Muñoz, Carlos Ávila-Nieto, Mónica Pérez, Edurne Garcia-Vidal, Daniel Pérez-Zsolt, Jordana Muñoz-Basagoiti, Dàlia Raïch-Regué, Nuria Izquierdo-Useros, Ignacio Blanco, Marc Noguera-Julián, Victor Guallar, Rosalba Lepore, Alfonso Valencia, Júlia Vergara-Alert, Bonaventura Clotet, Ester Ballana, Jorge Carrillo, Joaquim Segalés, Julià Blanco. SARS-CoV-2 B.1.351 (beta) variant shows enhanced infectivity in K18-hACE2 transgenic mice and expanded tropism to wildtype mice compared to B.1 variant. . 2021; ():1.

Chicago/Turabian Style

Ferran Tarrés-Freixas; Benjamin Trinité; Anna Pons-Grífols; Miguel Romero-Durana; Eva Riveira-Muñoz; Carlos Ávila-Nieto; Mónica Pérez; Edurne Garcia-Vidal; Daniel Pérez-Zsolt; Jordana Muñoz-Basagoiti; Dàlia Raïch-Regué; Nuria Izquierdo-Useros; Ignacio Blanco; Marc Noguera-Julián; Victor Guallar; Rosalba Lepore; Alfonso Valencia; Júlia Vergara-Alert; Bonaventura Clotet; Ester Ballana; Jorge Carrillo; Joaquim Segalés; Julià Blanco. 2021. "SARS-CoV-2 B.1.351 (beta) variant shows enhanced infectivity in K18-hACE2 transgenic mice and expanded tropism to wildtype mice compared to B.1 variant." , no. : 1.

Journal article
Published: 28 July 2021 in Life Science Alliance
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The use of high-dose of intravenous immunoglobulins (IVIGs) as immunomodulators for the treatment of COVID-19–affected individuals has shown promising results. IVIG reduced inflammation in these patients, who progressively restored respiratory function. However, little is known about how they may modulate immune responses in COVID-19 individuals. Here, we have analyzed the levels of 41 inflammatory biomarkers in plasma samples obtained at day 0 (pretreatment initiation), 3, 7, and 14 from five hospitalized COVID-19 patients treated with a 5-d course of 400 mg/kg/d of IVIG. The plasmatic levels of several cytokines (Tumor Necrosis Factor, IL-10, IL-5, and IL-7), chemokines (macrophage inflammatory protein-1α), growth/tissue repairing factors (hepatic growth factor), complement activation (C5a), and intestinal damage such as Fatty acid–binding protein 2 and LPS-binding protein showed a progressive decreasing trend during the next 2 wk after treatment initiation. This trend was not observed in IVIG-untreated COVID-19 patients. Thus, the administration of high-dose IVIG to hospitalized COVID-19 patients may improve their clinical evolution by modulating their hyperinflammatory and immunosuppressive status.

ACS Style

María Luisa Rodríguez de la Concepción; Erola Ainsua-Enrich; Esteban Reynaga; Carlos Ávila-Nieto; Jose Ramón Santos; Silvia Roure; Lourdes Mateu; Roger Paredes; Jordi Puig; Juan Manuel Jimenez; Nuria Izquierdo-Useros; Bonaventura Clotet; María Luisa Pedro-Botet; Jorge Carrillo. High-dose intravenous immunoglobulins might modulate inflammation in COVID-19 patients. Life Science Alliance 2021, 4, e202001009 .

AMA Style

María Luisa Rodríguez de la Concepción, Erola Ainsua-Enrich, Esteban Reynaga, Carlos Ávila-Nieto, Jose Ramón Santos, Silvia Roure, Lourdes Mateu, Roger Paredes, Jordi Puig, Juan Manuel Jimenez, Nuria Izquierdo-Useros, Bonaventura Clotet, María Luisa Pedro-Botet, Jorge Carrillo. High-dose intravenous immunoglobulins might modulate inflammation in COVID-19 patients. Life Science Alliance. 2021; 4 (9):e202001009.

Chicago/Turabian Style

María Luisa Rodríguez de la Concepción; Erola Ainsua-Enrich; Esteban Reynaga; Carlos Ávila-Nieto; Jose Ramón Santos; Silvia Roure; Lourdes Mateu; Roger Paredes; Jordi Puig; Juan Manuel Jimenez; Nuria Izquierdo-Useros; Bonaventura Clotet; María Luisa Pedro-Botet; Jorge Carrillo. 2021. "High-dose intravenous immunoglobulins might modulate inflammation in COVID-19 patients." Life Science Alliance 4, no. 9: e202001009.

Research article
Published: 20 July 2021 in Journal of Dental Research
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Oral mouthwashes decrease the infectivity of several respiratory viruses including SARS-CoV-2. However, the precise agents with antiviral activity in these oral rinses and their exact mechanism of action remain unknown. Here we show that cetylpyridinium chloride (CPC), a quaternary ammonium compound in many oral mouthwashes, reduces SARS-CoV-2 infectivity by inhibiting the viral fusion step with target cells after disrupting the integrity of the viral envelope. We also found that CPC-containing mouth rinses decreased more than a thousand times the infectivity of SARS-CoV-2 in vitro, while the corresponding vehicles had no effect. This activity was effective for different SARS-CoV-2 variants, including the B.1.1.7 or Alpha variant originally identified in United Kingdom, and in the presence of sterilized saliva. CPC-containing mouth rinses could therefore represent a cost-effective measure to reduce SARS-CoV-2 infectivity in saliva, aiding to reduce viral transmission from infected individuals regardless of the variants they are infected with.

ACS Style

J. Muñoz-Basagoiti; D. Perez-Zsolt; R. León; V. Blanc; D. Raïch-Regué; M. Cano-Sarabia; B. Trinité; E. Pradenas; J. Blanco; J. Gispert; B. Clotet; N. Izquierdo-Useros. Mouthwashes with CPC Reduce the Infectivity of SARS-CoV-2 Variants In Vitro. Journal of Dental Research 2021, 1 .

AMA Style

J. Muñoz-Basagoiti, D. Perez-Zsolt, R. León, V. Blanc, D. Raïch-Regué, M. Cano-Sarabia, B. Trinité, E. Pradenas, J. Blanco, J. Gispert, B. Clotet, N. Izquierdo-Useros. Mouthwashes with CPC Reduce the Infectivity of SARS-CoV-2 Variants In Vitro. Journal of Dental Research. 2021; ():1.

Chicago/Turabian Style

J. Muñoz-Basagoiti; D. Perez-Zsolt; R. León; V. Blanc; D. Raïch-Regué; M. Cano-Sarabia; B. Trinité; E. Pradenas; J. Blanco; J. Gispert; B. Clotet; N. Izquierdo-Useros. 2021. "Mouthwashes with CPC Reduce the Infectivity of SARS-CoV-2 Variants In Vitro." Journal of Dental Research , no. : 1.

Journal article
Published: 12 June 2021 in Viruses
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With the spread of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there is a need to assess the protection conferred by both previous infections and current vaccination. Here we tested the neutralizing activity of infected and/or vaccinated individuals against pseudoviruses expressing the spike of the original SARS-CoV-2 isolate Wuhan-Hu-1 (WH1), the D614G mutant and the B.1.1.7 variant. Our data show that parameters of natural infection (time from infection and nature of the infecting variant) determined cross-neutralization. Uninfected vaccinees showed a small reduction in neutralization against the B.1.1.7 variant compared to both the WH1 strain and the D614G mutant. Interestingly, upon vaccination, previously infected individuals developed more robust neutralizing responses against B.1.1.7, suggesting that vaccines can boost the neutralization breadth conferred by natural infection.

ACS Style

Benjamin Trinité; Edwards Pradenas; Silvia Marfil; Carla Rovirosa; Víctor Urrea; Ferran Tarrés-Freixas; Raquel Ortiz; Jordi Rodon; Júlia Vergara-Alert; Joaquim Segalés; Victor Guallar; Rosalba Lepore; Nuria Izquierdo-Useros; Glòria Trujillo; Jaume Trapé; Carolina González-Fernández; Antonia Flor; Rafel Pérez-Vidal; Ruth Toledo; Anna Chamorro; Roger Paredes; Ignacio Blanco; Eulàlia Grau; Marta Massanella; Jorge Carrillo; Bonaventura Clotet; Julià Blanco. Previous SARS-CoV-2 Infection Increases B.1.1.7 Cross-Neutralization by Vaccinated Individuals. Viruses 2021, 13, 1135 .

AMA Style

Benjamin Trinité, Edwards Pradenas, Silvia Marfil, Carla Rovirosa, Víctor Urrea, Ferran Tarrés-Freixas, Raquel Ortiz, Jordi Rodon, Júlia Vergara-Alert, Joaquim Segalés, Victor Guallar, Rosalba Lepore, Nuria Izquierdo-Useros, Glòria Trujillo, Jaume Trapé, Carolina González-Fernández, Antonia Flor, Rafel Pérez-Vidal, Ruth Toledo, Anna Chamorro, Roger Paredes, Ignacio Blanco, Eulàlia Grau, Marta Massanella, Jorge Carrillo, Bonaventura Clotet, Julià Blanco. Previous SARS-CoV-2 Infection Increases B.1.1.7 Cross-Neutralization by Vaccinated Individuals. Viruses. 2021; 13 (6):1135.

Chicago/Turabian Style

Benjamin Trinité; Edwards Pradenas; Silvia Marfil; Carla Rovirosa; Víctor Urrea; Ferran Tarrés-Freixas; Raquel Ortiz; Jordi Rodon; Júlia Vergara-Alert; Joaquim Segalés; Victor Guallar; Rosalba Lepore; Nuria Izquierdo-Useros; Glòria Trujillo; Jaume Trapé; Carolina González-Fernández; Antonia Flor; Rafel Pérez-Vidal; Ruth Toledo; Anna Chamorro; Roger Paredes; Ignacio Blanco; Eulàlia Grau; Marta Massanella; Jorge Carrillo; Bonaventura Clotet; Julià Blanco. 2021. "Previous SARS-CoV-2 Infection Increases B.1.1.7 Cross-Neutralization by Vaccinated Individuals." Viruses 13, no. 6: 1135.

Article
Published: 14 May 2021
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COVID-19 pandemic is not yet under control by vaccination, and effective antivirals are critical for preparedness. Here we report that macrophages and dendritic cells, key antigen presenting myeloid cells (APCs), are largely resistant to SARS-CoV-2 infection. APCs effectively captured viruses within cellular compartments that lead to antigen degradation. Macrophages sense SARS-CoV-2 and released higher levels of cytokines, including those related to cytokine storm in severe COVID-19. The sialic acid-binding Ig-like lectin 1 (Siglec-1/CD169) present on APCs, which interacts with sialylated gangliosides on membranes of retroviruses or filoviruses, also binds SARS-CoV-2 via GM1. Blockage of Siglec-1 receptors by monoclonal antibodies reduces SARS-CoV-2 uptake and transfer to susceptible target cells. APCs expressing Siglec-1 and carrying SARS-CoV-2 are found in pulmonary tissues of non-human primates. Single cell analysis reveals the in vivo induction of cytokines in those macrophages. Targeting Siglec-1 could offer cross-protection against SARS-CoV-2 and other enveloped viruses that exploit APCs for viral dissemination, including those yet to come in future outbreaks.

ACS Style

Daniel Perez-Zsolt; Jordana Munoz Basagoiti; Jordi Rodon; Marc Elousa; Dalia Raich Regue; Cristina Risco; Martin Sachse; Maria Pino; Sanjeev Gumber; Mirko Paiardini; Jakub Chojnacki; Itziar Erkizia; Xabier Muniz; Ester Ballana; Eva Riveira Munoz; Marc Noguera-Julian; Roger Paredes; Benjamin Trinite; Ferran Tarres Freixas; Ignacio Blanco; Victor Guallar; Jorge Carrillo; Julia Blanco; Amalio Telenti; Holger Heyn; Joaquim Segales; Bonaventura Clotet; Javier Martinez-Picado; Julia Vergara-Alert; Nuria Izquierdo-Useros. Siglec-1 on dendritic cells mediates SARS-CoV-2 trans-infection of target cells while on macrophages triggers proinflammatory responses. 2021, 1 .

AMA Style

Daniel Perez-Zsolt, Jordana Munoz Basagoiti, Jordi Rodon, Marc Elousa, Dalia Raich Regue, Cristina Risco, Martin Sachse, Maria Pino, Sanjeev Gumber, Mirko Paiardini, Jakub Chojnacki, Itziar Erkizia, Xabier Muniz, Ester Ballana, Eva Riveira Munoz, Marc Noguera-Julian, Roger Paredes, Benjamin Trinite, Ferran Tarres Freixas, Ignacio Blanco, Victor Guallar, Jorge Carrillo, Julia Blanco, Amalio Telenti, Holger Heyn, Joaquim Segales, Bonaventura Clotet, Javier Martinez-Picado, Julia Vergara-Alert, Nuria Izquierdo-Useros. Siglec-1 on dendritic cells mediates SARS-CoV-2 trans-infection of target cells while on macrophages triggers proinflammatory responses. . 2021; ():1.

Chicago/Turabian Style

Daniel Perez-Zsolt; Jordana Munoz Basagoiti; Jordi Rodon; Marc Elousa; Dalia Raich Regue; Cristina Risco; Martin Sachse; Maria Pino; Sanjeev Gumber; Mirko Paiardini; Jakub Chojnacki; Itziar Erkizia; Xabier Muniz; Ester Ballana; Eva Riveira Munoz; Marc Noguera-Julian; Roger Paredes; Benjamin Trinite; Ferran Tarres Freixas; Ignacio Blanco; Victor Guallar; Jorge Carrillo; Julia Blanco; Amalio Telenti; Holger Heyn; Joaquim Segales; Bonaventura Clotet; Javier Martinez-Picado; Julia Vergara-Alert; Nuria Izquierdo-Useros. 2021. "Siglec-1 on dendritic cells mediates SARS-CoV-2 trans-infection of target cells while on macrophages triggers proinflammatory responses." , no. : 1.

Original research article
Published: 25 March 2021 in Frontiers in Pharmacology
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There is an urgent need to identify therapeutics for the treatment of Coronavirus disease 2019 (COVID-19). Although different antivirals are given for the clinical management of SARS-CoV-2 infection, their efficacy is still under evaluation. Here, we have screened existing drugs approved for human use in a variety of diseases, to compare how they counteract SARS-CoV-2-induced cytopathic effect and viral replication in vitro. Among the potential 72 antivirals tested herein that were previously proposed to inhibit SARS-CoV-2 infection, only 18 % had an IC50 below 25 µM or 102 IU/ml. These included plitidepsin, novel cathepsin inhibitors, nelfinavir mesylate hydrate, interferon 2-alpha, interferon-gamma, fenofibrate, camostat along the well-known remdesivir and chloroquine derivatives. Plitidepsin was the only clinically approved drug displaying nanomolar efficacy. Four of these families, including novel cathepsin inhibitors, blocked viral entry in a cell—type specific manner. Since the most effective antivirals usually combine therapies that tackle the virus at different steps of infection, we also assessed several drug combinations. Although no particular synergy was found, inhibitory combinations did not reduce their antiviral activity. Thus, these combinations could decrease the potential emergence of resistant viruses. Antivirals prioritized herein identify novel compounds and their mode of action, while independently replicating the activity of a reduced proportion of drugs which are mostly approved for clinical use. Combinations of these drugs should be tested in animal models to inform the design of fast track clinical trials.

ACS Style

Jordi Rodon; Jordana Muñoz-Basagoiti; Daniel Perez-Zsolt; Marc Noguera-Julian; Roger Paredes; Lourdes Mateu; Carles Quiñones; Carles Perez; Itziar Erkizia; Ignacio Blanco; Alfonso Valencia; Víctor Guallar; Jorge Carrillo; Julià Blanco; Joaquim Segalés; Bonaventura Clotet; Júlia Vergara-Alert; Nuria Izquierdo-Useros. Identification of Plitidepsin as Potent Inhibitor of SARS-CoV-2-Induced Cytopathic Effect After a Drug Repurposing Screen. Frontiers in Pharmacology 2021, 12, 646676 .

AMA Style

Jordi Rodon, Jordana Muñoz-Basagoiti, Daniel Perez-Zsolt, Marc Noguera-Julian, Roger Paredes, Lourdes Mateu, Carles Quiñones, Carles Perez, Itziar Erkizia, Ignacio Blanco, Alfonso Valencia, Víctor Guallar, Jorge Carrillo, Julià Blanco, Joaquim Segalés, Bonaventura Clotet, Júlia Vergara-Alert, Nuria Izquierdo-Useros. Identification of Plitidepsin as Potent Inhibitor of SARS-CoV-2-Induced Cytopathic Effect After a Drug Repurposing Screen. Frontiers in Pharmacology. 2021; 12 ():646676.

Chicago/Turabian Style

Jordi Rodon; Jordana Muñoz-Basagoiti; Daniel Perez-Zsolt; Marc Noguera-Julian; Roger Paredes; Lourdes Mateu; Carles Quiñones; Carles Perez; Itziar Erkizia; Ignacio Blanco; Alfonso Valencia; Víctor Guallar; Jorge Carrillo; Julià Blanco; Joaquim Segalés; Bonaventura Clotet; Júlia Vergara-Alert; Nuria Izquierdo-Useros. 2021. "Identification of Plitidepsin as Potent Inhibitor of SARS-CoV-2-Induced Cytopathic Effect After a Drug Repurposing Screen." Frontiers in Pharmacology 12, no. : 646676.

Preprint content
Published: 05 March 2021
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To assess the potential impact of predominant circulating SARS-CoV-2 variants on neutralizing activity of infected and/or vaccinated individuals, we analyzed neutralization of pseudoviruses expressing the spike of the original Wuhan strain, the D614G and B.1.1.7 variants. Our data show that parameters of natural infection (time from infection and infecting variant) determined cross-neutralization. Importantly, upon vaccination, previously infected individuals developed equivalent B.1.1.7 and Wuhan neutralizing responses. In contrast, uninfected vaccinees showed reduced neutralization against B.1.1.7. Funding This study was funded by Grifols, the Departament de Salut of the Generalitat de Catalunya, the Spanish Health Institute Carlos III, CERCA Programme/Generalitat de Catalunya, and the crowdfunding initiatives #joemcorono, BonPreu/Esclat and Correos.

ACS Style

Benjamin Trinité; Edwards Pradenas; Silvia Marfil; Carla Rovirosa; Víctor Urrea; Ferran Tarrés-Freixas; Raquel Ortiz; Júlia Vergara-Alert; Joaquim Segalés; Victor Guallar; Rosalba Lepore; Nuria Izquierdo-Useros; Glòria Trujillo; Jaume Trapé; Carolina González-Fernández; Antonia Flor; Rafel Pérez-Vidal; Anna Chamorro; Roger Paredes; Ignacio Blanco; Eulalia Grau; Marta Massanella; Jorge Carrillo; Bonaventura Clotet; Julià Blanco. Previous SARS-CoV-2 infection increases B.1.1.7 cross-neutralization by vaccinated individuals. 2021, 1 .

AMA Style

Benjamin Trinité, Edwards Pradenas, Silvia Marfil, Carla Rovirosa, Víctor Urrea, Ferran Tarrés-Freixas, Raquel Ortiz, Júlia Vergara-Alert, Joaquim Segalés, Victor Guallar, Rosalba Lepore, Nuria Izquierdo-Useros, Glòria Trujillo, Jaume Trapé, Carolina González-Fernández, Antonia Flor, Rafel Pérez-Vidal, Anna Chamorro, Roger Paredes, Ignacio Blanco, Eulalia Grau, Marta Massanella, Jorge Carrillo, Bonaventura Clotet, Julià Blanco. Previous SARS-CoV-2 infection increases B.1.1.7 cross-neutralization by vaccinated individuals. . 2021; ():1.

Chicago/Turabian Style

Benjamin Trinité; Edwards Pradenas; Silvia Marfil; Carla Rovirosa; Víctor Urrea; Ferran Tarrés-Freixas; Raquel Ortiz; Júlia Vergara-Alert; Joaquim Segalés; Victor Guallar; Rosalba Lepore; Nuria Izquierdo-Useros; Glòria Trujillo; Jaume Trapé; Carolina González-Fernández; Antonia Flor; Rafel Pérez-Vidal; Anna Chamorro; Roger Paredes; Ignacio Blanco; Eulalia Grau; Marta Massanella; Jorge Carrillo; Bonaventura Clotet; Julià Blanco. 2021. "Previous SARS-CoV-2 infection increases B.1.1.7 cross-neutralization by vaccinated individuals." , no. : 1.

Review
Published: 18 January 2021 in Membranes
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Viruses rely on the cellular machinery to replicate and propagate within newly infected individuals. Thus, viral entry into the host cell sets up the stage for productive infection and disease progression. Different viruses exploit distinct cellular receptors for viral entry; however, numerous viral internalization mechanisms are shared by very diverse viral families. Such is the case of Ebola virus (EBOV), which belongs to the filoviridae family, and the recently emerged coronavirus SARS-CoV-2. These two highly pathogenic viruses can exploit very similar endocytic routes to productively infect target cells. This convergence has sped up the experimental assessment of clinical therapies against SARS-CoV-2 previously found to be effective for EBOV, and facilitated their expedited clinical testing. Here we review how the viral entry processes and subsequent replication and egress strategies of EBOV and SARS-CoV-2 can overlap, and how our previous knowledge on antivirals, antibodies, and vaccines against EBOV has boosted the search for effective countermeasures against the new coronavirus. As preparedness is key to contain forthcoming pandemics, lessons learned over the years by combating life-threatening viruses should help us to quickly deploy effective tools against novel emerging viruses.

ACS Style

Jordana Muñoz-Basagoiti; Daniel Perez-Zsolt; Jorge Carrillo; Julià Blanco; Bonaventura Clotet; Nuria Izquierdo-Useros. SARS-CoV-2 Cellular Infection and Therapeutic Opportunities: Lessons Learned from Ebola Virus. Membranes 2021, 11, 64 .

AMA Style

Jordana Muñoz-Basagoiti, Daniel Perez-Zsolt, Jorge Carrillo, Julià Blanco, Bonaventura Clotet, Nuria Izquierdo-Useros. SARS-CoV-2 Cellular Infection and Therapeutic Opportunities: Lessons Learned from Ebola Virus. Membranes. 2021; 11 (1):64.

Chicago/Turabian Style

Jordana Muñoz-Basagoiti; Daniel Perez-Zsolt; Jorge Carrillo; Julià Blanco; Bonaventura Clotet; Nuria Izquierdo-Useros. 2021. "SARS-CoV-2 Cellular Infection and Therapeutic Opportunities: Lessons Learned from Ebola Virus." Membranes 11, no. 1: 64.

Research article
Published: 14 January 2021 in Journal of Extracellular Vesicles
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The identification of individuals with null alleles enables studying how the loss of gene function affects infection. We previously described a non‐functional variant in SIGLEC1, which encodes the myeloid‐cell receptor Siglec‐1/CD169 implicated in HIV‐1 cell‐to‐cell transmission. Here we report a significant association between the SIGLEC1 null variant and extrapulmonary dissemination of Mycobacterium tuberculosis (Mtb) in two clinical cohorts comprising 6,256 individuals. Local spread of bacteria within the lung is apparent in Mtb‐infected Siglec‐1 knockout mice which, despite having similar bacterial load, developed more extensive lesions compared to wild type mice. We find that Siglec‐1 is necessary to induce antigen presentation through extracellular vesicle uptake. We postulate that lack of Siglec‐1 delays the onset of protective immunity against Mtb by limiting antigen exchange via extracellular vesicles, allowing for an early local spread of mycobacteria that increases the risk for extrapulmonary dissemination.

ACS Style

Susana Benet; Cristina Gálvez; Francis Drobniewski; Irina Kontsevaya; Lilibeth Arias; Marta Monguió‐Tortajada; Itziar Erkizia; Victor Urrea; Ruo‐Yan Ong; Marina Luquin; Maeva Dupont; Jakub Chojnacki; Judith Dalmau; Paula Cardona; Olivier Neyrolles; Geanncarlo Lugo‐Villarino; Christel Vérollet; Esther Julián; Hansjakob Furrer; Huldrych F. Günthard; Paul R. Crocker; Gustavo Tapia; Francesc E. Borràs; Jacques Fellay; Paul J. McLaren; Amalio Telenti; Pere‐Joan Cardona; Bonaventura Clotet; Cristina Vilaplana; Javier Martinez‐Picado; Nuria Izquierdo‐Useros. Dissemination of Mycobacterium tuberculosis is associated to a SIGLEC1 null variant that limits antigen exchange via trafficking extracellular vesicles. Journal of Extracellular Vesicles 2021, 10, 1 .

AMA Style

Susana Benet, Cristina Gálvez, Francis Drobniewski, Irina Kontsevaya, Lilibeth Arias, Marta Monguió‐Tortajada, Itziar Erkizia, Victor Urrea, Ruo‐Yan Ong, Marina Luquin, Maeva Dupont, Jakub Chojnacki, Judith Dalmau, Paula Cardona, Olivier Neyrolles, Geanncarlo Lugo‐Villarino, Christel Vérollet, Esther Julián, Hansjakob Furrer, Huldrych F. Günthard, Paul R. Crocker, Gustavo Tapia, Francesc E. Borràs, Jacques Fellay, Paul J. McLaren, Amalio Telenti, Pere‐Joan Cardona, Bonaventura Clotet, Cristina Vilaplana, Javier Martinez‐Picado, Nuria Izquierdo‐Useros. Dissemination of Mycobacterium tuberculosis is associated to a SIGLEC1 null variant that limits antigen exchange via trafficking extracellular vesicles. Journal of Extracellular Vesicles. 2021; 10 (3):1.

Chicago/Turabian Style

Susana Benet; Cristina Gálvez; Francis Drobniewski; Irina Kontsevaya; Lilibeth Arias; Marta Monguió‐Tortajada; Itziar Erkizia; Victor Urrea; Ruo‐Yan Ong; Marina Luquin; Maeva Dupont; Jakub Chojnacki; Judith Dalmau; Paula Cardona; Olivier Neyrolles; Geanncarlo Lugo‐Villarino; Christel Vérollet; Esther Julián; Hansjakob Furrer; Huldrych F. Günthard; Paul R. Crocker; Gustavo Tapia; Francesc E. Borràs; Jacques Fellay; Paul J. McLaren; Amalio Telenti; Pere‐Joan Cardona; Bonaventura Clotet; Cristina Vilaplana; Javier Martinez‐Picado; Nuria Izquierdo‐Useros. 2021. "Dissemination of Mycobacterium tuberculosis is associated to a SIGLEC1 null variant that limits antigen exchange via trafficking extracellular vesicles." Journal of Extracellular Vesicles 10, no. 3: 1.

Preprint content
Published: 07 January 2021
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Reinfections with SARS-CoV-2 have already been documented in humans, although its real incidence is currently unknown. Besides having great impact on public health, this phenomenon raises the question if immunity generated by a single infection is sufficient to provide sterilizing/protective immunity to a subsequent SARS-CoV-2 re-exposure. The Golden Syrian hamster is a manageable animal model to explore immunological mechanisms able to counteract COVID-19, as it recapitulates pathological aspects of mild to moderately affected patients. Here, we report that SARS-CoV-2-inoculated hamsters resolve infection in the upper and lower respiratory tracts within seven days upon inoculation with the Cat01 (G614) SARS-CoV-2 isolate. Three weeks after primary challenge, and despite high titers of neutralizing antibodies, half of the animals were susceptible to reinfection by both identical (Cat01, G614) and variant (WA/1, D614) SARS-CoV-2 isolates. However, upon re-inoculation, only nasal tissues were transiently infected with much lower viral replication than those observed after the first inoculation. These data indicate that a primary SARS-CoV-2 infection is not sufficient to elicit a sterilizing immunity in hamster models but protects against lung disease.

ACS Style

Marco Brustolin; Jordi Rodon; María Luisa Rodríguez de la Concepción; Carlos Ávila-Nieto; Guillermo Cantero; Mónica Pérez; Nigeer Te; Marc Noguera-Julián; Víctor Guallar; Alfonso Valencia; Núria Roca; Nuria Izquierdo-Useros; Julià Blanco; Bonaventura Clotet; Albert Bensaid; Jorge Carrillo; Júlia Vergara-Alert; Joaquim Segalés. Protection against reinfection with D614- or G614-SARS-CoV-2 isolates in hamsters. 2021, 1 .

AMA Style

Marco Brustolin, Jordi Rodon, María Luisa Rodríguez de la Concepción, Carlos Ávila-Nieto, Guillermo Cantero, Mónica Pérez, Nigeer Te, Marc Noguera-Julián, Víctor Guallar, Alfonso Valencia, Núria Roca, Nuria Izquierdo-Useros, Julià Blanco, Bonaventura Clotet, Albert Bensaid, Jorge Carrillo, Júlia Vergara-Alert, Joaquim Segalés. Protection against reinfection with D614- or G614-SARS-CoV-2 isolates in hamsters. . 2021; ():1.

Chicago/Turabian Style

Marco Brustolin; Jordi Rodon; María Luisa Rodríguez de la Concepción; Carlos Ávila-Nieto; Guillermo Cantero; Mónica Pérez; Nigeer Te; Marc Noguera-Julián; Víctor Guallar; Alfonso Valencia; Núria Roca; Nuria Izquierdo-Useros; Julià Blanco; Bonaventura Clotet; Albert Bensaid; Jorge Carrillo; Júlia Vergara-Alert; Joaquim Segalés. 2021. "Protection against reinfection with D614- or G614-SARS-CoV-2 isolates in hamsters." , no. : 1.

Preprint content
Published: 21 December 2020
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Oral mouthwashes decrease the infectivity of several respiratory viruses including SARS-CoV-2. However, the precise agents with antiviral activity present in these oral rinses and their exact mechanism of action remain unknown. Here we show that Cetylpyridinium chloride (CPC), a quaternary ammonium compound present in many oral mouthwashes, reduces SARS-CoV-2 infectivity by inhibiting the viral fusion step with target cells after disrupting the integrity of the viral envelope. We also found that CPC-containing mouth rinses decreased more than a thousand times the infectivity of SARS-CoV-2 in vitro, while the corresponding vehicles had no effect. This activity was effective for different SARS-CoV-2 variants, including the B.1.1.7 variant, predominant in UK, also in the presence of sterilized saliva. CPC-containing mouth rinses could therefore represent a cost-effective measure to reduce SARS-CoV-2 infectivity in saliva, aiding to reduce viral transmission from infected individuals regardless of the variants they are infected with.

ACS Style

Jordana Muñoz-Basagoiti; Daniel Perez-Zsolt; Rubén León; Vanessa Blanc; Dàlia Raïch-Regué; Mary Cano-Sarabia; Benjamin Trinité; Edwards Pradenas; Julià Blanco; Joan Gispert; Bonaventura Clotet; Nuria Izquierdo-Useros. Cetylpyridinium chloride-containing mouthwashes reduce the infectivity of SARS-CoV-2 variants in vitro. 2020, 1 .

AMA Style

Jordana Muñoz-Basagoiti, Daniel Perez-Zsolt, Rubén León, Vanessa Blanc, Dàlia Raïch-Regué, Mary Cano-Sarabia, Benjamin Trinité, Edwards Pradenas, Julià Blanco, Joan Gispert, Bonaventura Clotet, Nuria Izquierdo-Useros. Cetylpyridinium chloride-containing mouthwashes reduce the infectivity of SARS-CoV-2 variants in vitro. . 2020; ():1.

Chicago/Turabian Style

Jordana Muñoz-Basagoiti; Daniel Perez-Zsolt; Rubén León; Vanessa Blanc; Dàlia Raïch-Regué; Mary Cano-Sarabia; Benjamin Trinité; Edwards Pradenas; Julià Blanco; Joan Gispert; Bonaventura Clotet; Nuria Izquierdo-Useros. 2020. "Cetylpyridinium chloride-containing mouthwashes reduce the infectivity of SARS-CoV-2 variants in vitro." , no. : 1.

Short communication
Published: 07 November 2020 in Biochemical and Biophysical Research Communications
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The magnitude and the quality of humoral responses against SARS-CoV-2 have been associated with clinical outcome. Although the elicitation of humoral responses against different viral proteins is rapid and occurs in most infected individuals, its magnitude is highly variable among them and positively correlates with COVID-19 disease severity. This rapid response is characterized by the almost concomitant appearance of virus-specific IgG, IgA and IgM antibodies that contain neutralizing antibodies directed against different epitopes of the Spike glycoprotein. Of particularly interest, the antibodies against domain of the Spike that interacts with the cellular receptor ACE2, known as the receptor binding domain (RBD), are present in most infected individuals and are block viral entry and infectivity. Such neutralizing antibodies protect different animal species when administered before virus exposure; therefore, its elicitation is the main target of current vaccine approaches and their clinical use as recombinant monoclonal antibodies (mAbs) is being explored. Yet, little information exists on the duration of humoral responses during natural infection. This is a key issue that will impact the management of the pandemic and determine the utility of seroconversion studies and the level of herd immunity. Certainly, several cases of reinfection have been reported, suggesting that immunity could be transient, as reported for other coronaviruses. In summary, although the kinetics of the generation of antibodies against SASR-CoV-2 and their protective activity have been clearly defined, their role in COVID-19 pathogenesis and the length of these responses are still open questions.

ACS Style

Jorge Carrillo; Nuria Izquierdo-Useros; Carlos Ávila-Nieto; Edwards Pradenas; Bonaventura Clotet; Julià Blanco. Humoral immune responses and neutralizing antibodies against SARS-CoV-2; implications in pathogenesis and protective immunity. Biochemical and Biophysical Research Communications 2020, 538, 187 -191.

AMA Style

Jorge Carrillo, Nuria Izquierdo-Useros, Carlos Ávila-Nieto, Edwards Pradenas, Bonaventura Clotet, Julià Blanco. Humoral immune responses and neutralizing antibodies against SARS-CoV-2; implications in pathogenesis and protective immunity. Biochemical and Biophysical Research Communications. 2020; 538 ():187-191.

Chicago/Turabian Style

Jorge Carrillo; Nuria Izquierdo-Useros; Carlos Ávila-Nieto; Edwards Pradenas; Bonaventura Clotet; Julià Blanco. 2020. "Humoral immune responses and neutralizing antibodies against SARS-CoV-2; implications in pathogenesis and protective immunity." Biochemical and Biophysical Research Communications 538, no. : 187-191.

Agricultural sciences
Published: 18 September 2020 in Proceedings of the National Academy of Sciences
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19, is considered a zoonotic pathogen mainly transmitted human to human. Few reports indicate that pets may be exposed to the virus. The present report describes a cat suffering from severe respiratory distress and thrombocytopenia living with a family with several members affected by COVID-19. Clinical signs of the cat prompted humanitarian euthanasia and a detailed postmortem investigation to assess whether a COVID-19−like disease was causing the condition. Necropsy results showed the animal suffered from feline hypertrophic cardiomyopathy and severe pulmonary edema and thrombosis. SARS-CoV-2 RNA was only detected in nasal swab, nasal turbinates, and mesenteric lymph node, but no evidence of histopathological lesions compatible with a viral infection were detected. The cat seroconverted against SARS-CoV-2, further evidencing a productive infection in this animal. We conclude that the animal had a subclinical SARS-CoV-2 infection concomitant to an unrelated cardiomyopathy that led to euthanasia.

ACS Style

Joaquim Segalés; Mariona Puig; Jordi Rodon; Carlos Avila-Nieto; Jorge Carrillo; Guillermo Cantero; Maria Teresa Terrón; Sílvia Cruz; Mariona Parera; Marc Noguera-Julián; Nuria Izquierdo-Useros; Víctor Guallar; Enric Vidal; Alfonso Valencia; Ignacio Blanco; Julià Blanco; Bonaventura Clotet; Júlia Vergara-Alert. Detection of SARS-CoV-2 in a cat owned by a COVID-19−affected patient in Spain. Proceedings of the National Academy of Sciences 2020, 117, 24790 -24793.

AMA Style

Joaquim Segalés, Mariona Puig, Jordi Rodon, Carlos Avila-Nieto, Jorge Carrillo, Guillermo Cantero, Maria Teresa Terrón, Sílvia Cruz, Mariona Parera, Marc Noguera-Julián, Nuria Izquierdo-Useros, Víctor Guallar, Enric Vidal, Alfonso Valencia, Ignacio Blanco, Julià Blanco, Bonaventura Clotet, Júlia Vergara-Alert. Detection of SARS-CoV-2 in a cat owned by a COVID-19−affected patient in Spain. Proceedings of the National Academy of Sciences. 2020; 117 (40):24790-24793.

Chicago/Turabian Style

Joaquim Segalés; Mariona Puig; Jordi Rodon; Carlos Avila-Nieto; Jorge Carrillo; Guillermo Cantero; Maria Teresa Terrón; Sílvia Cruz; Mariona Parera; Marc Noguera-Julián; Nuria Izquierdo-Useros; Víctor Guallar; Enric Vidal; Alfonso Valencia; Ignacio Blanco; Julià Blanco; Bonaventura Clotet; Júlia Vergara-Alert. 2020. "Detection of SARS-CoV-2 in a cat owned by a COVID-19−affected patient in Spain." Proceedings of the National Academy of Sciences 117, no. 40: 24790-24793.

Preprint content
Published: 24 April 2020
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There is an urgent need to identify therapeutics for the treatment of Coronavirus diseases 2019 (COVID-19). Although different antivirals are given for the clinical management of SARS-CoV-2 infection, their efficacy is still under evaluation. Here, we have screened existing drugs approved for human use in a variety of diseases, to compare how they counteract SARS-CoV-2-induced cytopathic effect and viral replication in vitro. Among the potential 72 antivirals tested herein that were previously proposed to inhibit SARS-CoV-2 infection, only 18% had an IC50 below 25 μM or 102 IU/mL. These included plitidepsin, novel cathepsin inhibitors, nelfinavir mesylate hydrate, interferon 2-alpha, interferon-gamma, fenofibrate, camostat along the well-known remdesivir and chloroquine derivatives. Plitidepsin was the only clinically approved drug displaying nanomolar efficacy. Four of these families, including novel cathepsin inhibitors, blocked viral entry in a cell-type specific manner. Since the most effective antivirals usually combine therapies that tackle the virus at different steps of infection, we also assessed several drug combinations. Although no particular synergy was found, inhibitory combinations did not reduce their antiviral activity. Thus, these combinations could decrease the potential emergence of resistant viruses. Antivirals prioritized herein identify novel compounds and their mode of action, while independently replicating the activity of a reduced proportion of drugs which are mostly approved for clinical use. Combinations of these drugs should be tested in animal models to inform the design of fast track clinical trials.

ACS Style

Jordi Rodon; Jordana Muñoz-Basagoiti; Daniel Perez-Zsolt; Marc Noguera-Julian; Roger Paredes; Lourdes Mateu; Carles Quiñones; Itziar Erkizia; Ignacio Blanco; Alfonso Valencia; Víctor Guallar; Jorge Carrillo; Julià Blanco; Joaquim Segalés; Bonaventura Clotet; Júlia Vergara-Alert; Nuria Izquierdo-Useros. Identification of Plitidepsin as Potent Inhibitor of SARS-CoV-2-Induced Cytopathic Effect after a Drug Repurposing Screen. 2020, 1 .

AMA Style

Jordi Rodon, Jordana Muñoz-Basagoiti, Daniel Perez-Zsolt, Marc Noguera-Julian, Roger Paredes, Lourdes Mateu, Carles Quiñones, Itziar Erkizia, Ignacio Blanco, Alfonso Valencia, Víctor Guallar, Jorge Carrillo, Julià Blanco, Joaquim Segalés, Bonaventura Clotet, Júlia Vergara-Alert, Nuria Izquierdo-Useros. Identification of Plitidepsin as Potent Inhibitor of SARS-CoV-2-Induced Cytopathic Effect after a Drug Repurposing Screen. . 2020; ():1.

Chicago/Turabian Style

Jordi Rodon; Jordana Muñoz-Basagoiti; Daniel Perez-Zsolt; Marc Noguera-Julian; Roger Paredes; Lourdes Mateu; Carles Quiñones; Itziar Erkizia; Ignacio Blanco; Alfonso Valencia; Víctor Guallar; Jorge Carrillo; Julià Blanco; Joaquim Segalés; Bonaventura Clotet; Júlia Vergara-Alert; Nuria Izquierdo-Useros. 2020. "Identification of Plitidepsin as Potent Inhibitor of SARS-CoV-2-Induced Cytopathic Effect after a Drug Repurposing Screen." , no. : 1.

Abstract
Published: 01 January 2020 in Proceedings
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Arenaviruses are enveloped viruses that cause hemorrhagic fever outbreaks in humans and still lack an effective antiviral treatment. Upon early infection, these viruses target dendritic cells (DCs), which can promote systemic viral dissemination, contributing to pathogenesis. We have previously described that Siglec-1, a sialic acid Ig-like binding lectin-1 expressed on DCs interacts with different enveloped viruses and promotes their capture within a virus-containing compartment. Such is the case of HIV-1 or Ebola virus, which display sialylated gangliosides on their viral envelope that are effectively recognized by Siglec-1. Here, we aimed to study if Siglec-1 on DCs also interacts with arenaviruses such as Junin. We produced non-infectious Junin viral-like particles (Junin-VLPs) tagged with fluorescent Egfp by transfecting a plasmid encoding the structural Junin Z protein on HEK-293T cells. Junin-VLPs were added to a Raji cell line stably transfected with Siglec-1 or to monocyte-derived DCs activated or not with either Interferon-α or lipopolysaccharide. Viral uptake was analyzed by FACS or confocal microscopy in the presence of an anti-Siglec-1 monoclonal antibody (mAb) or an isotype control. Statistical differences were assessed with the indicated tests. Raji Siglec-1 cells captured a higher number of Junin-VLPs than Raji cells, and this was blocked with an anti-Siglec-1 mAb (P = 0.0159; Mann–Whitney). On primary DCs, activation enhanced Junin-VLP capture (P = 0.0024; paired t-test) and Siglec-1 expression. Furthermore, pre-incubation with an anti-Siglec-1 mAb on activated DCs blocked Junin-VLP uptake (P ≤ 0.0002; one sample t-test), while an isotype control did not. Forty-nine percent of the activated DCs analyzed by confocal microscopy captured Junin-VLPs within a Siglec-1+ virus-containing compartment. Moreover, when HIV-1 was also added, 97% of those compartments retained both viruses. Thus, we conclude that Siglec-1 is a new receptor involved in arenavirus uptake in DCs and could represent a novel target for an anti-arenavirus treatment.

ACS Style

Xabier Muniz-Trabudua; Cristina Borio; Marcos Bilen; Itziar Erkizia; Daniel Perez-Zsolt; Susana Benet; Javier Martinez-Picado; Nuria Izquierdo-Useros. Siglec-1 Expressed on Dendritic Cells is a New Receptor Implicated in Arenavirus Uptake. Proceedings 2020, 50, 90 .

AMA Style

Xabier Muniz-Trabudua, Cristina Borio, Marcos Bilen, Itziar Erkizia, Daniel Perez-Zsolt, Susana Benet, Javier Martinez-Picado, Nuria Izquierdo-Useros. Siglec-1 Expressed on Dendritic Cells is a New Receptor Implicated in Arenavirus Uptake. Proceedings. 2020; 50 (1):90.

Chicago/Turabian Style

Xabier Muniz-Trabudua; Cristina Borio; Marcos Bilen; Itziar Erkizia; Daniel Perez-Zsolt; Susana Benet; Javier Martinez-Picado; Nuria Izquierdo-Useros. 2020. "Siglec-1 Expressed on Dendritic Cells is a New Receptor Implicated in Arenavirus Uptake." Proceedings 50, no. 1: 90.

Conference paper
Published: 01 January 2020 in Proceedings
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Viral infections in humans cause a huge burden in worldwide healthcare that has increased due to the emergence of new pathogenic viruses, such as in the recent Ebola virus (EBOV) outbreaks. Viral particles in body fluids are often at very low levels, making diagnosis difficult. In order to address this problem, we have developed a new detection platform to isolate and detect different enveloped viruses. We have recently identified that sialic acid-binding Ig‑like lectin 1 (Siglec-1/CD169) is one cellular receptor used by EBOV and HIV-1 to enter myeloid cells, key target cells for infection and pathogenesis. For viral uptake, the V-set domain of this myeloid cell receptor recognizes the gangliosides of viral membranes that were dragged during viral budding from the plasma membrane of infected cells. We took advantage of this specific interaction between Siglec‑1 and viral gangliosides to develop a new detection methodology. We have generated a recombinant protein that contains the V-set domain of Siglec-1 fused to the human IgG Fc domain for anchoring in latex beads. These coated beads allow the isolation of viral particles and their measurement by flow cytometry. We have tested its efficacy to detect HIV-1 and EBOV and its specificity by using anti-Siglec‑1 antibodies that prevent the interaction and serve as a negative control. To test the capacity of our method, we used synthetic liposomes to assess the effect of ganglioside concentration in membranes as well as the size of viral particles. This methodology would facilitate the diagnosis of infections by concentrating viral particles in a fast and direct method. At a time when global human mobility facilitates the dissemination of infectious agents, our approach represents a rapid and effective method to maximize the identification of both known and emerging enveloped viruses as part of public health viral surveillance strategies.

ACS Style

Patricia Resa-Infante; Itziar Erkizia; Jon Ander Nieto-Garai; Maier Lorizate; Nuria Izquierdo-Useros; Javier Martinez-Picado. Novel Methodology for the Detection of Enveloped Viruses. Proceedings 2020, 50, 1 .

AMA Style

Patricia Resa-Infante, Itziar Erkizia, Jon Ander Nieto-Garai, Maier Lorizate, Nuria Izquierdo-Useros, Javier Martinez-Picado. Novel Methodology for the Detection of Enveloped Viruses. Proceedings. 2020; 50 (1):1.

Chicago/Turabian Style

Patricia Resa-Infante; Itziar Erkizia; Jon Ander Nieto-Garai; Maier Lorizate; Nuria Izquierdo-Useros; Javier Martinez-Picado. 2020. "Novel Methodology for the Detection of Enveloped Viruses." Proceedings 50, no. 1: 1.

Review
Published: 19 December 2019 in Viruses
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Dendritic cells (DCs) are among the first cells that recognize incoming viruses at the mucosal portals of entry. Initial interaction between DCs and viruses facilitates cell activation and migration to secondary lymphoid tissues, where these antigen presenting cells (APCs) prime specific adaptive immune responses. Some viruses, however, have evolved strategies to subvert the migratory capacity of DCs as a way to disseminate infection systemically. Here we focus on the role of Siglec-1, a sialic acid-binding type I lectin receptor potently upregulated by type I interferons on DCs, that acts as a double edge sword, containing viral replication through the induction of antiviral immunity, but also favoring viral spread within tissues. Such is the case for distant enveloped viruses like human immunodeficiency virus (HIV)-1 or Ebola virus (EBOV), which incorporate sialic acid-containing gangliosides on their viral membrane and are effectively recognized by Siglec-1. Here we review how Siglec-1 is highly induced on the surface of human DCs upon viral infection, the way this impacts different antigen presentation pathways, and how enveloped viruses have evolved to exploit these APC functions as a potent dissemination strategy in different anatomical compartments.

ACS Style

Daniel Perez-Zsolt; Javier Martinez-Picado; Nuria Izquierdo-Useros. When Dendritic Cells Go Viral: The Role of Siglec-1 in Host Defense and Dissemination of Enveloped Viruses. Viruses 2019, 12, 8 .

AMA Style

Daniel Perez-Zsolt, Javier Martinez-Picado, Nuria Izquierdo-Useros. When Dendritic Cells Go Viral: The Role of Siglec-1 in Host Defense and Dissemination of Enveloped Viruses. Viruses. 2019; 12 (1):8.

Chicago/Turabian Style

Daniel Perez-Zsolt; Javier Martinez-Picado; Nuria Izquierdo-Useros. 2019. "When Dendritic Cells Go Viral: The Role of Siglec-1 in Host Defense and Dissemination of Enveloped Viruses." Viruses 12, no. 1: 8.

Preprint content
Published: 12 November 2019
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While tuberculosis (TB) is a risk factor in HIV-1-infected individuals, the mechanisms by whichMycobacterium tuberculosisworsens HIV-1 pathogenesis remain poorly understood. Recently, we showed that HIV-1 infection and spread are exacerbated in macrophages exposed to TB-associated microenvironments due to tunneling nanotube (TNT) formation. To identify molecular factors associated with TNT function, we performed a transcriptomic analysis in these macrophages, and revealed the up-regulation of the lectin receptor Siglec-1. We demonstrate Siglec-1 expression depends on TB-mediated production of type I interferon. In co-infected non-human primates, Siglec-1 is highly expressed by alveolar macrophages, whose abundance correlates with pathology and activation of the type I interferon/STAT1 pathway. Intriguingly, Siglec-1 expression localizes exclusively on microtubule-containing TNT that are long and carry HIV-1 cargo. Siglec-1 depletion in macrophages decreases TNT length, diminishes HIV-1 capture and cell-to-cell transfer, and abrogates TB-driven exacerbation of HIV-1 infection. Altogether, we uncover a deleterious role for Siglec-1 in TB-HIV-1 co-infection, and its localization on TNT opens new avenues to understand cell-to-cell viral spread.

ACS Style

Maeva Dupont; Shanti Souriant; Luciana Balboa; Thien-Phong Vu Manh; Karine Pingris; Stella Rousset; Céline Cougoule; Yoann Rombouts; Renaud Poincloux; Myriam Ben Neji; Carolina Allers; Deepak Kaushal; Marcelo J. Kuroda; Susana Benet; Javier Martinez-Picado; Nuria Izquierdo-Useros; Maria Del Carmen Sasiain; Isabelle Maridonneau-Parini; Olivier Neyrolles; Christel Vérollet; Geanncarlo Lugo-Villarino. Tuberculosis-associated IFN-I induces Siglec-1 on tunneling nanotubes and favors HIV-1 spread in macrophages. 2019, 836155 .

AMA Style

Maeva Dupont, Shanti Souriant, Luciana Balboa, Thien-Phong Vu Manh, Karine Pingris, Stella Rousset, Céline Cougoule, Yoann Rombouts, Renaud Poincloux, Myriam Ben Neji, Carolina Allers, Deepak Kaushal, Marcelo J. Kuroda, Susana Benet, Javier Martinez-Picado, Nuria Izquierdo-Useros, Maria Del Carmen Sasiain, Isabelle Maridonneau-Parini, Olivier Neyrolles, Christel Vérollet, Geanncarlo Lugo-Villarino. Tuberculosis-associated IFN-I induces Siglec-1 on tunneling nanotubes and favors HIV-1 spread in macrophages. . 2019; ():836155.

Chicago/Turabian Style

Maeva Dupont; Shanti Souriant; Luciana Balboa; Thien-Phong Vu Manh; Karine Pingris; Stella Rousset; Céline Cougoule; Yoann Rombouts; Renaud Poincloux; Myriam Ben Neji; Carolina Allers; Deepak Kaushal; Marcelo J. Kuroda; Susana Benet; Javier Martinez-Picado; Nuria Izquierdo-Useros; Maria Del Carmen Sasiain; Isabelle Maridonneau-Parini; Olivier Neyrolles; Christel Vérollet; Geanncarlo Lugo-Villarino. 2019. "Tuberculosis-associated IFN-I induces Siglec-1 on tunneling nanotubes and favors HIV-1 spread in macrophages." , no. : 836155.