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http://conacyt.repositorioinstitucional.mx/jspui/handle/1000/2155| The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) envelope (E) protein harbors a conserved BH3-like motif | |
| Vincent Navratil. Sonia Longhi. Christophe Combet. | |
| Acceso Abierto | |
| Atribución-NoComercial-SinDerivadas | |
| 10.1101/2020.04.09.033522 | |
| Following the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) in 2002 and Middle East Respiratory Syndrome coronavirus (MERS-CoV) in 2012, the novel coronavirus SARS-CoV-2 emerged at the end of 2019 as a highly pathogenic infectious agent that rapidly spread around the world. SARS-CoV-2 shares high sequence homology with SARS-CoV and causes acute, highly lethal pneumonia coronavirus disease 2019 (COVID-19) with clinical symptoms similar to those reported for SARS-CoV. Like other betacoronaviruses, SARS-CoV-2 encode four major structural proteins: Spike (S), Membrane (M), Nucleocapsid (N) and Envelope (E). SARS-CoV E protein is abundant in infected cells and plays a crucial role in viral particle assembly. Moreover, SARS coronaviruses lacking E are attenuated in vivo, suggesting that CoV E may act as a critical virulence factor not only in SARS-CoV but also in the case of the new coronavirus SARS-CoV-2. Ectopic expression of SARS-CoV E was previously shown to trigger apoptosis (cell suicide) of T lymphocytes, lymphopenia being a common feature observed in fatal cases following viral infections. Importantly, T-cell apoptosis was shown to involve interaction between the C-terminal region of SARS-CoV E and the Bcl-2 family member Bcl-xL, which acts as a potent anti-apoptotic protein. Here we provide the first observation that the SARS-CoV E and SARS-CoV-2 E proteins share a conserved Bcl-2 Homology 3 (BH3)-like motif in their C-terminal region, a well-studied motif shown to be necessary for SARS-CoV E binding to Bcl-xL. We used available sequence data for SARS-CoV-2 and related coronaviruses, in combination with structural information, to study the structure to biological activity relationships of SARS-CoV-2 E in relation with its BH3-like motif. Our analysis of the SARS-CoV E interactome further revealed that the predicted SARS-CoV-2 network is extensively wired to the Bcl-2 apoptotic switch. Research is therefore needed to establish if SARS-CoV-2 E targets prosurvival Bcl-2 homologs to modulate cell viability, as part of a coronavirus strategy to interfere with apoptosis. The identification of small molecules (or the repurposing of existing drugs) able to disrupt SARS-CoV-2 E BH3-mediated interactions might provide a targeted therapeutic approach for COVID-19 treatment. Recombinant SARS-CoV-2 expressing an E protein with a deleted or mutated BH3-like motif might also be of interest for the design of a live, attenuated vaccine. | |
| www.biorxiv.org | |
| 2020 | |
| Artículo | |
| https://www.biorxiv.org/content/10.1101/2020.04.09.033522v2.full.pdf | |
| Inglés | |
| VIRUS RESPIRATORIOS | |
| Aparece en las colecciones: | Artículos científicos |
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