SARS-CoV-2 Spike Protein Destabilizes Microvascular Homeostasis

Panigrahi, Soumya; Goswami, Tamal; Ferrari, Brian; Antonelli, Christopher J.; Bazdar, Douglas A.; Gilmore, Hannah; Freeman, Michael L.; Lederman, Michael M.; Sieg, Scott F.

doi:10.1128/spectrum.00735-21

Cited by 15 publications

(11 citation statements)

References 55 publications

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“…Further, S protein disrupted human cardiac pericytes function and triggered increased production of proapoptotic factors in pericytes, causing endothelial cells death [79]. In support of this, administration of the S protein promoted dysfunction of human endothelial cells as evidenced by, for example, increased expression of the von Willebrand factor [80]. Other reports indicate that S1 can directly induce coagulation by competitive binding to both soluble and cellular heparan sulfate/heparin (an anticoagulant) [81][82][83][84], while cell-free hemoglobin, as a hypoxia counterbalance, cannot attenuate disruption of endothelial barrier function, oxidative stress, or inflammatory responses in human pulmonary arterial endothelial cells exposed to S1 [85].…”

Section: Box 2 Other Types Of Covid-19 Vaccinementioning

confidence: 96%

Adverse effects of COVID-19 mRNA vaccines: the spike hypothesis

Trougakos

Terpos

Alexopoulos

et al. 2022

Trends in Molecular Medicine

158

144

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Section: Box 2 Other Types Of Covid-19 Vaccinementioning

confidence: 96%

Adverse effects of COVID-19 mRNA vaccines: the spike hypothesis

Trougakos

Terpos

Alexopoulos

et al. 2022

Trends in Molecular Medicine

158

144

View full text Add to dashboard Cite

“…Many researchers have reported that systemic pathological events (excessive immune response, hyper-inflammation, and release of proinflammatory cytokines and chemokines) in COVID-19 infection trigger macro and microvascular thrombosis [20][21][22]. Additionally, the recruitment and activation of leukocytes and platelets result in the progression of coagulopathy via intravascular generation of thrombin.…”

Section: Discussionmentioning

confidence: 99%

A snake venom-analog peptide that inhibits SARS-CoV-2 and papain-like protease displays antithrombotic activity in mice arterial thrombosis model, without interfering with bleeding time

et al. 2023

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Background (p-BthTX-I)2 K, a dimeric analog peptide derived from the C-terminal region of phospholipase A2-like bothropstoxin-I (p-BthTX-I), is resistant to plasma proteolysis and inhibits severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains with weak cytotoxic effects. Complications of SARS-CoV-2 infection include vascular problems and increased risk of thrombosis; therefore, studies to identify new drugs for treating SARS-CoV-2 infections that also inhibit thrombosis and minimize the risk of bleeding are required. Objectives To determine whether (p-BthTX-I)2 K affects the hemostatic system. Methods Platelet aggregation was induced by collagen, arachidonic acid, and adenosine diphosphate (ADP) in the Chronolog Lumi-aggregometer. The coagulation activity was evaluated by determining activated partial thromboplastin clotting time (aPTT) and prothrombin time (PT) with (p-BthTX-I)2 K (5.0–434.5 µg) or 0.9% NaCl. Arterial thrombosis was induced with a 540 nm laser and 3.5–20 mg kg− 1 Rose Bengal in the carotid artery of male C57BL/6J mice using (p-BthTX-I)2 K. Bleeding time was determined in mouse tails immersed in saline at 37 °C after (p-BthTX-I)2 K (4.0 mg/kg and 8.0 mg/kg) or saline administration. Results (p-BthTX-I)2 K prolonged the aPTT and PT by blocking kallikrein and FXa-like activities. Moreover, (p-BthTX-I)2 K inhibited ADP-, collagen-, and arachidonic acid-induced platelet aggregation in a dose-dependent manner. Further, low concentrations of (p-BthTX-I)2 K extended the time to artery occlusion by the formed thrombus. However, (p-BthTX-I)2 K did not prolong the bleeding time in the mouse model of arterial thrombosis. Conclusion These results demonstrate the antithrombotic activity of the peptide (p-BthTX-I)2 K possibly by kallikrein inhibition, suggesting its strong biotechnological potential.

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“…Several experts have suggested that SARS-CoV-2 replicates in endothelial cells; this replication might be further promoted if the endothelium has already been damaged [122] . The virus spike protein's disorganising effects on the microvasculature were reviewed recently [123] . Interestingly, autopsy material indeed showed early lesions in capillaries and microthrombi in arterioles; as well as some damage to larger vessels [124] .…”

Section: Putative Mechanisms Underlying Met's Protective Effectsmentioning

confidence: 99%