Coronaviruses are a large family of enveloped RNA viruses found in numerous animal species. They are well known for their ability to cross species barriers and have been transmitted from bats or intermediate hosts to humans on several occasions. Four of the seven human coronaviruses (hCoVs) are responsible for approximately 20% of common colds (hCoV-229E, -NL63, -OC43, -HKU1). Two others (SARS-CoV-1 and MERS-CoV) cause severe and frequently lethal respiratory syndromes but have only spread to very limited extents in the human population. In contrast the most recent human hCoV, SARS-CoV-2, while exhibiting intermediate pathogenicity, has a profound impact on public health due to its enormous spread. In this review, we discuss which initial features of the SARS-CoV-2 Spike protein and subsequent adaptations to the new human host may have helped this pathogen to cause the COVID-19 pandemic. Our focus is on host forces driving changes in the Spike protein and their consequences for virus infectivity, pathogenicity, immune evasion and resistance to preventive or therapeutic agents. In addition, we briefly address the significance and perspectives of broad-spectrum therapeutics and vaccines.
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http://dx.doi.org/10.3390/v16020177 | DOI Listing |
J Infect Dis
January 2025
Moderna, Inc., Cambridge, MA 02142, USA.
Background: mRNA-1283 is an investigational COVID-19 mRNA vaccine encoding the receptor-binding and N-terminal domains of the SARS-CoV-2 spike protein in contrast to the original mRNA-1273, which encodes the full-length spike protein.
Methods: A phase 2a, dose-ranging, observer-blind, randomized study (NCT05137236) conducted in adults (≥18 years) previously vaccinated with mRNA-1273 evaluated the safety and immunogenicity of a single dose of mRNA-1283 (2.5, 5, and 10 µg) and its bivalent formulation, mRNA-1283.
J Virol
January 2025
Infection Biology Unit, German Primate Centre - Leibniz Institute for Primate Research, Göttingen, Germany.
The naturally occurring mutation E484D in the spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can render viral entry ACE2 independent and imdevimab resistant. Here, we investigated whether the cellular proteins ASGR1, DC-SIGN, and TMEM106B, which interact with the viral S protein, can contribute to these processes. Employing S protein-pseudotyped particles, we found that expression of ASGR1 or DC-SIGN jointly with TMEM106B allowed for robust entry of mutant E484D into otherwise non-susceptible cells, while this effect was not observed upon separate expression of the single proteins and upon infection with SARS-CoV-2 wild type (WT).
View Article and Find Full Text PDFEuro Surveill
January 2025
RKI-SOEP-2 Study Group is acknowledged at the end of the article.
BackgroundThe first Corona Monitoring Nationwide (RKI-SOEP) study (October 2020-February 2021) found a low pre-vaccine SARS-CoV-2 antibody seroprevalence (2.1%) in the German adult population (≥ 18 years).AimThe objective of this second RKI-SOEP (RKI-SOEP-2) study in November 2021-March 2022 was to estimate the prevalence of SARS-CoV-2-specific anti-spike and/or anti-nucleocapsid (anti-N) IgG antibodies (combined seroprevalence), past infection based on infection-induced seroprevalence (anti-N), and basic immunisation (at least two antigen contacts through vaccination or infection) in individuals aged ≥ 14 years.
View Article and Find Full Text PDFACS Appl Mater Interfaces
January 2025
Suzhou CureMed Biopharma Technology Co., Ltd., Suzhou 215125, China.
The emergence of mRNA vaccines offers great promise and a potent platform in combating various diseases, notably COVID-19. Nevertheless, challenges such as inherent instability and potential side effects of current delivery systems underscore the critical need for the advancement of stable, safe, and efficacious mRNA vaccines. In this study, a robust mRNA vaccine (cmRNA-1130) eliciting potent immune activation has been developed from a biodegradable lipid with eight ester bonds in the branched tail (AX4) and synthetic circular mRNA (cmRNA) encoding the trimeric Delta receptor binding domain of the SARS-CoV-2 spike protein.
View Article and Find Full Text PDFMol Biotechnol
January 2025
Department of Biological Sciences, School of Medical and Life Sciences, Sunway University, Bandar Sunway, 47500, Petaling Jaya, Selangor, Malaysia.
The etiological agent for the coronavirus disease 2019 (COVID-19), the SARS-CoV-2, caused a global pandemic. Although mRNA, viral-vectored, DNA, and recombinant protein vaccine candidates were effective against the SARS-CoV-2 Wuhan strain, the emergence of SARS-CoV-2 variants of concern (VOCs) reduced the protective efficacies of these vaccines. This necessitates the need for effective and accelerated vaccine development against mutated VOCs.
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