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Nanobodies or variable antigen-binding domains (VH) derived from heavy chain-only antibodies (HcAb) occurring in the Camelidae family offer certain superior physicochemical characteristics like enhanced stability, solubility, and low immunogenicity compared to conventional antibodies. Their efficient antigen-binding capabilities make them a preferred choice for next-generation small biologics. In the present work, we design an anti-SARS-CoV-2 bi-paratopic nanobody drug conjugate by screening a nanobody database.

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Although much has been learned about the entry mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), many details of the entry mechanisms of seasonal human coronaviruses (HCoVs) remain less well understood. In the present study, we used 293T cell lines stably expressing angiotensin converting enzyme (ACE2), aminopeptidase N (APN), or transmembrane serine protease 2 (TMPRSS2), which support high-level transduction of lentiviral pseudoviruses bearing spike proteins of seasonal HCoVs, HCoV-NL63, -229E, or -HKU1, respectively, to compare spike processing and virus entry pathways among these viruses. Our results showed that the entry of HCoV-NL63, -229E, and -HKU1 pseudoviruses into cells is sensitive to endosomal acidification inhibitors (chloroquine and NHCl), indicating entry via the endocytosis route.

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Introduction: Vaccines to prevent important infections involving, e.g. influenza viruses, severe acute respiratory syndrome-causing coronaviruses (e.

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Rethinking Optimal Immunogens to Face SARS-CoV-2 Evolution Through Vaccination.

Influenza Other Respir Viruses

January 2025

Área de Investigación en Vacunas, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana, Valencia, Spain.

SARS-CoV-2, which originated in China in late 2019, quickly fueled the global COVID-19 pandemic, profoundly impacting health and the economy worldwide. A series of vaccines, mostly based on the full SARS-CoV-2 Spike protein, were rapidly developed, showing excellent humoral and cellular responses and high efficacy against both symptomatic infection and severe disease. However, viral evolution and the waning humoral neutralizing responses strongly challenged vaccine long term effectiveness, mainly against symptomatic infection, making necessary a strategy of repeated and updated booster shots.

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