Improved binding of SARS-CoV-2 Envelope protein to tight junction-associated PALS1 could play a key role in COVID-19 pathogenesis

Michela Sali, Alessandro Arcovito, Maurizio Sanguinetti, Giovanni Scambia, Andrea Urbani, Flavio De Maio, Ettore Lo Cascio, Stefano Della Longa, Bruno Tilocca, Paola Roncada

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

8 Citazioni (Scopus)

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.
Lingua originaleEnglish
pagine (da-a)1-6
Numero di pagine6
RivistaMicrobes and Infection
Volume2020
DOI
Stato di pubblicazionePubblicato - 2020

Keywords

  • COVID-19
  • Envelope protein
  • PALS1
  • SARS-CoV-2
  • Tight junctions

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