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Research paper thumbnail of Identification of potential inhibitors of protein-protein interaction useful to fight against Ebola and other highly pathogenic viruses

Research paper thumbnail of Prime-boost vaccination with BNT162b2 induces high neutralizing activity against SARS-CoV-2 variants in naïve and COVID-19 convalescent individuals

Open Forum Infectious Diseases

Objectives To investigate the neutralizing response against SARS-CoV-2 Variants of Concern (VoC) ... more Objectives To investigate the neutralizing response against SARS-CoV-2 Variants of Concern (VoC) during COVID-19 convalescence and after vaccination. Methods COVID-19 convalescents and naïve individuals were tested for neutralizing activity against SARS-CoV-2 VoC Alpha, Beta, Gamma and Delta at 1- and 7-months post-infection and 4-6 weeks after BNT162b2 vaccination. Results Vaccination induced a high neutralizing response in naïve individuals. Interestingly, vaccination of convalescent patients induced a boosting response that was able to neutralize all VoC at high titers. Conclusions Vaccination with BNT162b2 induced high levels of neutralization against SARS-CoV-2 VoC in most patients, this is especially beneficial in COVID-19 convalescent individuals.

Research paper thumbnail of DC/L-SIGN recognition of spike glycoprotein promotes SARS-CoV-2 trans-infection and can be inhibited by a glycomimetic antagonist

The efficient spread of SARS-CoV-2 resulted in a pandemic that is unique in modern history. Despi... more The efficient spread of SARS-CoV-2 resulted in a pandemic that is unique in modern history. Despite early identification of ACE2 as the receptor for viral spike protein, much remains to be understood about the molecular events behind viral dissemination. We evaluated the contribution of C-type lectin receptors (CLRS) of antigen-presenting cells, widely present in air mucosa and lung tissue. DC-SIGN, L-SIGN, Langerin and MGL bind to diverse glycans of the spike using multiple interaction areas. Using pseudovirus and cells derived from monocytes or T-lymphocytes, we demonstrate that while virus capture by the CLRs examined does not allow direct cell infection, DC/L-SIGN, among these receptors, promote virus transfer to permissive ACE2+ cells. A glycomimetic compound designed against DC-SIGN, enable inhibition of this process. Thus, we described a mechanism potentiating viral capture and spreading of infection. Early involvement of APCs opens new avenues for understanding and treating the imbalanced innate immune response observed in COVID-19 pathogenesis

Research paper thumbnail of Real-time RT-PCR assay to detect Granada virus and the related Massilia and Arrabida phleboviruses

Background: Granada virus belongs to the genus Phlebovirus within the Naples serocomplex and was ... more Background: Granada virus belongs to the genus Phlebovirus within the Naples serocomplex and was detected for the first time in sand flies from Spain in 2003. Seroprevalence studies have revealed that Granada virus may infect humans with most cases being asymptomatic. Moreover, recent studies in vector samples revealed that the related Massilia and Arrabida phleboviruses could be also circulating in Spain. The objective of this study was to develop and assess a new sensitive real-time RT-PCR assay for Granada virus diagnosis able to detect the related phleboviruses Massilia and Arrabida. Methods: Two specific primers and one unique probe to detect Granada, Massilia and Arrabida viruses, without differentiating between them, were designed targeting the conserved L-segment of their genome. Sensitivity was assessed using 10-fold serial dilutions of quantified in vitro DNA samples. Specificity was evaluated by testing different genomic RNA extracted from other representative phleboviruses. The new assay was used for virus detection in sand flies collected in 2012 from the Balearic Archipelago, a touristic hotspot in the Mediterranean. Results: The real-time RT-PCR assay exhibited a sensitivity per reaction of 19 copies for Granada and Arrabida, and 16 copies for Massilia. No other related phleboviruses were detected. From the 37 pools of sand fly samples studied from four different Balearic Islands, we detected one positive in the island of Cabrera. Conclusions: To our knowledge, the method described here is the first real-time RT-PCR designed to detect Granada virus and the related Massilia and Arrabida phleboviruses. The study demonstrated that this is a rapid, robust and reliable assay for the accurate diagnosis of human infections as well as for virus surveillance in vectors.

Research paper thumbnail of Survey of Crimean-Congo Hemorrhagic Fever Enzootic Focus, Spain, 2011–2015

During 2011–2015, we conducted a Crimean-Congo hemorrhagic fever virus (CCHFV) survey in captured... more During 2011–2015, we conducted a Crimean-Congo hemorrhagic fever virus (CCHFV) survey in captured ticks that were feeding mainly on wild and domestic ungulates in Spain, where presence of this virus had been reported previously. We detected CCHFV RNA in Hyalomma lusitanicum and H. marginatum ticks for 3 of the 5 years. The rate of infected ticks was 2.78% (44/1,579), which was similar to those for other countries in Europe with endemic foci for CCHFV (Kosovo, Bulgaria, and Albania). These data confirm the established spread of CCHFV into western Europe. Phylogenetic study of the small RNA segment showed Africa-3 clade as the only genotype identified, although we observed cocirculation of genetic variants during 2011 and 2015. We could not rule out genetic reassortments because of lack of sequence data for the medium and large RNA segments of the virus genome.

Research paper thumbnail of Identification of potential inhibitors of protein-protein interaction useful to fight against Ebola and other highly pathogenic viruses

Research paper thumbnail of Prime-boost vaccination with BNT162b2 induces high neutralizing activity against SARS-CoV-2 variants in naïve and COVID-19 convalescent individuals

Open Forum Infectious Diseases

Objectives To investigate the neutralizing response against SARS-CoV-2 Variants of Concern (VoC) ... more Objectives To investigate the neutralizing response against SARS-CoV-2 Variants of Concern (VoC) during COVID-19 convalescence and after vaccination. Methods COVID-19 convalescents and naïve individuals were tested for neutralizing activity against SARS-CoV-2 VoC Alpha, Beta, Gamma and Delta at 1- and 7-months post-infection and 4-6 weeks after BNT162b2 vaccination. Results Vaccination induced a high neutralizing response in naïve individuals. Interestingly, vaccination of convalescent patients induced a boosting response that was able to neutralize all VoC at high titers. Conclusions Vaccination with BNT162b2 induced high levels of neutralization against SARS-CoV-2 VoC in most patients, this is especially beneficial in COVID-19 convalescent individuals.

Research paper thumbnail of DC/L-SIGN recognition of spike glycoprotein promotes SARS-CoV-2 trans-infection and can be inhibited by a glycomimetic antagonist

The efficient spread of SARS-CoV-2 resulted in a pandemic that is unique in modern history. Despi... more The efficient spread of SARS-CoV-2 resulted in a pandemic that is unique in modern history. Despite early identification of ACE2 as the receptor for viral spike protein, much remains to be understood about the molecular events behind viral dissemination. We evaluated the contribution of C-type lectin receptors (CLRS) of antigen-presenting cells, widely present in air mucosa and lung tissue. DC-SIGN, L-SIGN, Langerin and MGL bind to diverse glycans of the spike using multiple interaction areas. Using pseudovirus and cells derived from monocytes or T-lymphocytes, we demonstrate that while virus capture by the CLRs examined does not allow direct cell infection, DC/L-SIGN, among these receptors, promote virus transfer to permissive ACE2+ cells. A glycomimetic compound designed against DC-SIGN, enable inhibition of this process. Thus, we described a mechanism potentiating viral capture and spreading of infection. Early involvement of APCs opens new avenues for understanding and treating the imbalanced innate immune response observed in COVID-19 pathogenesis

Research paper thumbnail of Real-time RT-PCR assay to detect Granada virus and the related Massilia and Arrabida phleboviruses

Background: Granada virus belongs to the genus Phlebovirus within the Naples serocomplex and was ... more Background: Granada virus belongs to the genus Phlebovirus within the Naples serocomplex and was detected for the first time in sand flies from Spain in 2003. Seroprevalence studies have revealed that Granada virus may infect humans with most cases being asymptomatic. Moreover, recent studies in vector samples revealed that the related Massilia and Arrabida phleboviruses could be also circulating in Spain. The objective of this study was to develop and assess a new sensitive real-time RT-PCR assay for Granada virus diagnosis able to detect the related phleboviruses Massilia and Arrabida. Methods: Two specific primers and one unique probe to detect Granada, Massilia and Arrabida viruses, without differentiating between them, were designed targeting the conserved L-segment of their genome. Sensitivity was assessed using 10-fold serial dilutions of quantified in vitro DNA samples. Specificity was evaluated by testing different genomic RNA extracted from other representative phleboviruses. The new assay was used for virus detection in sand flies collected in 2012 from the Balearic Archipelago, a touristic hotspot in the Mediterranean. Results: The real-time RT-PCR assay exhibited a sensitivity per reaction of 19 copies for Granada and Arrabida, and 16 copies for Massilia. No other related phleboviruses were detected. From the 37 pools of sand fly samples studied from four different Balearic Islands, we detected one positive in the island of Cabrera. Conclusions: To our knowledge, the method described here is the first real-time RT-PCR designed to detect Granada virus and the related Massilia and Arrabida phleboviruses. The study demonstrated that this is a rapid, robust and reliable assay for the accurate diagnosis of human infections as well as for virus surveillance in vectors.

Research paper thumbnail of Survey of Crimean-Congo Hemorrhagic Fever Enzootic Focus, Spain, 2011–2015

During 2011–2015, we conducted a Crimean-Congo hemorrhagic fever virus (CCHFV) survey in captured... more During 2011–2015, we conducted a Crimean-Congo hemorrhagic fever virus (CCHFV) survey in captured ticks that were feeding mainly on wild and domestic ungulates in Spain, where presence of this virus had been reported previously. We detected CCHFV RNA in Hyalomma lusitanicum and H. marginatum ticks for 3 of the 5 years. The rate of infected ticks was 2.78% (44/1,579), which was similar to those for other countries in Europe with endemic foci for CCHFV (Kosovo, Bulgaria, and Albania). These data confirm the established spread of CCHFV into western Europe. Phylogenetic study of the small RNA segment showed Africa-3 clade as the only genotype identified, although we observed cocirculation of genetic variants during 2011 and 2015. We could not rule out genetic reassortments because of lack of sequence data for the medium and large RNA segments of the virus genome.

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