After two years since the outbreak, the COVID-19 pandemic remains a global public health emergency. SARS-CoV-2 variants with substitutions on the spike (S) protein emerge increasing the risk of immune evasion and cross-species transmission. Here, we analyzed the evolution of the S protein as recorded in 276,712 samples collected before the start of vaccination efforts. Our analysis shows that most variants destabilize the S protein trimer, increase its conformational heterogeneity and improve the odds of the recognition by the host cell receptor. Most frequent substitutions promote overall hydrophobicity by replacing charged amino acids, reducing stabilizing local interactions in the unbound S protein trimer. Moreover, our results identify "forbidden" regions that rarely show any sequence variation, and which are related to conformational changes occurring upon fusion. These results are significant for understanding the structure and function of SARS-CoV-2 related proteins which is a critical step in vaccine development and epidemiological surveillance.
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http://dx.doi.org/10.1016/j.jmb.2022.167637 | DOI Listing |
Neurochem Res
January 2025
Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder characterized by cognitive decline. Despite extensive research, therapeutic options remain limited. Varenicline, an αβ nicotinic acetylcholine receptor agonist, shows promise in enhancing cognitive function.
View Article and Find Full Text PDFHum Vaccin Immunother
December 2025
Crucell Integration, Janssen Research and Development, Beerse, Belgium.
We conducted a randomized, Phase 2 trial to assess the safety and humoral immunogenicity of reduced doses/dose volume of the standard dose of Ad26.COV2.S COVID-19 vaccine (5 × 10 viral particles [vp]) in healthy adolescents aged 12-17 years.
View Article and Find Full Text PDFPept Sci (Hoboken)
November 2024
Department of Pediatrics, Section of Hematology/Oncology, The University of Chicago, Chicago, Illinois 60637, United States of America.
The COVID-19 pandemic drove a uniquely fervent pursuit to explore the potential of peptide, antibody, protein, and small-molecule based antiviral agents against severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). The interaction between the SARS-CoV2 spike protein with the angiotensin-converting enzyme 2 (ACE2) receptor that mediates viral cell entry was a particularly interesting target given its well described protein-protein interaction (PPI). This PPI is mediated by an α-helical portion of ACE2 binding to the receptor binding domain (RBD) of the spike protein and thought to be susceptible to blockade through molecular mimicry.
View Article and Find Full Text PDFACS Omega
January 2025
School of Life Sciences, Beijing University of Chinese Medicine, Beijing 102488, China.
In phage display technology, exogenous DNA is inserted into the phage genome, which generates a fusion protein with the phage coat protein, facilitates expression and promotes biological activity. This approach is primarily used to screen antibody libraries owing to its high library capacity and fast technical cycle; additionally, various types of genetically altered antibodies can be easily produced. In this study, we fused the pIII structural protein of the M13K07 phage with a scFv created by connecting the VH and VL domains of an anti-IFN-γ antibody.
View Article and Find Full Text PDFHeliyon
January 2025
Pediatric Infectious Diseases Unit, Department of Pediatrics, Gregorio Marañón University Hospital, Madrid, Spain.
Objective: The aim of this prospective cohort study is to analyse the humoral and cellular vaccine responses in paediatric heart transplant recipients (HTR, n = 12), and compare it with the response in healthy controls (HC, n = 14). All participants were 5-18 years old and vaccinated with mRNA vaccine against SARS-CoV-2 between December 2021 and May 2022.
Methods: The humoral response was measured by quantifying antibody titers against SARS-CoV-2 spike protein (anti-S).
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