Research reveals that a viral toxin may contribute to the severity of COVID-19 Coronavirus Disease COVID Protein SARSCoV2 SpikeProtein Vascular NatureComms
By Dr. Priyom Bose, Ph.D.Dec 14 2022Reviewed by Benedette Cuffari, M.Sc. The rapid spread of the severe acute respiratory syndrome coronavirus 2 resulted in the coronavirus disease 2019 pandemic. Although most individuals infected with SARS-CoV-2 are asymptomatic or experience mild symptoms, some succumb to severe infection with chronic lung injury and acute respiratory distress syndrome .
SARS-CoV-2 belongs to the Coronaviridae family and possesses a positive-sense ribonucleic acid genome that encodes four structural proteins, of which include the spike , membrane , nucleocapsid , and envelope , and non-structural proteins. In addition to binding to ACE2, the S glycoprotein is also associated with various other cell-surface factors, such as integrins and heparan sulfate-containing proteoglycans . These factors predominantly promote SARS-CoV-2 entry into the host cell. The association of the viral S protein with these factors has been linked with signaling pathways that contribute to lung pathology.
About the study A recent Nature Communications study analyzed whether the SARS-CoV-2 S protein influences endothelial and epithelial barrier dysfunction in vitro and vascular leak in vivo. Key findings The in vitro and in vivo experimental findings indicated that virion-associated full-length S, soluble trimeric S, and recombinant RBD could trigger barrier dysfunction. The first and second mechanisms by which SARS-CoV-2 induces barrier dysfunction is due to its interactions with ACE2-negative non-permissive cells and during the infection of virus-permissive cells.
To this end, clinical samples of COVID-19 patients sufficiently facilitated barrier dysfunction. Thus, in addition to its role in viral entry to the host cell, the S protein also interacts with glycosaminoglycans and integrins to induce vascular leakage through activation of the transforming growth factor beta pathway.
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