1. Improved binding of SARS-CoV-2 Envelope protein to tight junction-associated PALS1 could play a key role in COVID-19 pathogenesis.
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De Maio, Flavio, Lo Cascio, Ettore, Babini, Gabriele, Sali, Michela, Della Longa, Stefano, Tilocca, Bruno, Roncada, Paola, Arcovito, Alessandro, Sanguinetti, Maurizio, Scambia, Giovanni, and Urbani, Andrea
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COVID-19 , *SARS-CoV-2 , *TIGHT junctions , *PROTEIN conformation , *SARS disease , *AMINO acid sequence , *TISSUE remodeling , *PROTEINS - Abstract
The Envelope (E) protein of SARS-CoV-2 is the most enigmatic protein among the four structural ones. Most of its current knowledge is based on the direct comparison to the SARS E protein, initially mistakenly undervalued and subsequently proved to be a key factor in the ER-Golgi localization and in tight junction disruption. We compared the genomic sequences of E protein of SARS-CoV-2, SARS-CoV and the closely related genomes of bats and pangolins obtained from the GISAID and GenBank databases. When compared to the known SARS E protein, we observed a significant difference in amino acid sequence in the C-terminal end of SARS-CoV-2 E protein. Subsequently, in silico modelling analyses of E proteins conformation and docking provide evidences of a strengthened binding of SARS-CoV-2 E protein with the tight junction-associated PALS1 protein. Based on our computational evidences and on data related to SARS-CoV, we believe that SARS-CoV-2 E protein interferes more stably with PALS1 leading to an enhanced epithelial barrier disruption, amplifying the inflammatory processes, and promoting tissue remodelling. These findings raise a warning on the underestimated role of the E protein in the pathogenic mechanism and open the route to detailed experimental investigations. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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