Recent studies suggest that the main mechanism disrupting the endothelial barrier occurs in several stages: First, a direct effect on the endothelial cells that causes an immune response of the vascular endothelium (endotheliitis) and endothelial dysfunction. It is currently believed that in addition to being a respiratory disease, COVID-19 might also be a вЂvascular diseaseвЂ™ ( Lee et al., 2021), as it may result in a leaky vascular barrier and increased expression of von Willebrand factor (VWF) ( Siddiqi et al., 2020), responsible for increased coagulation, cytokine release, and inflammation ( Siddiqi et al., 2020 Teuwen et al., 2020 Aid et al., 2020 Potus et al., 2020 Wazny et al., 2020 Pum et al., 2021 Barbosa et al., 2021 Lin et al., 2020 Matarese et al., 2020 Xiao et al., 2020). Recent observations suggest that these pathologies are mainly due to increased coagulation and vascular dysfunction ( Lee et al., 2021 Libby and LГјscher, 2020 Siddiqi et al., 2020). Interestingly, additional pathologies have been observed, such as hypoxemia and cytokine storm which, in some cases, lead to heart and kidney failure, and neurological symptoms. After the initial phase of the viral infection, ~ 30% of patients hospitalized with COVID-19 develop severe disease with progressive lung damage, known as severe acute respiratory syndrome (SARS), and a severe immune response. By late September 2021, coronavirus had infected more than 220 million people worldwide, causing over 4.5 million deaths. IntroductionД¬oronavirus disease (COVID-19) caused by the 2019 novel coronavirus (2019-nCoV/SARS-CoV-2) led to a global pandemic in 2020. Overall, this work identifies the SARS-CoV-2 proteins that might be most detrimental in terms of endothelial dysfunction, thereby shedding light on vascular aspects of COVID-19. While validating the PPI network model, we found that the tight junction (TJ) proteins cadherin-5, ZO-1, and ОІ-catenin are affected by nsp2, nsp5_c145a, and nsp7 consistent with the model prediction. We further applied our PPI model to identify the role of each SARS-CoV-2 protein in other tissues affected by coronavirus disease (COVID-19). Using propagation-based analysis of a proteinвЂ“protein interaction (PPI) network, we predicted the endothelial proteins affected by the viral proteins that potentially mediate these effects.

Whereas most proteins induced significant changes in endothelial permeability, nsp2, nsp5_c145a (catalytic dead mutant of nsp5), and nsp7 also reduced CD31, and increased von Willebrand factor expression and IL-6, suggesting endothelial dysfunction. We cloned and expressed 26 of these proteins in human cells and characterized the endothelial response to overexpression of each, individually. The SARS-CoV-2 genome encodes 29 proteins, whose contribution to the disease manifestations, and especially endothelial complications, is unknown. It affects several vital organs, seemingly through a pathological effect on endothelial cells. Severe acute respiratory syndrome (SARS)-CoV-2 infection leads to severe disease associated with cytokine storm, vascular dysfunction, coagulation, and progressive lung damage.

Dead effect 2