Monaghan-Nichols, P. | Search bioRxiv

bioRxiv2024

Simple and rapid lectin-based detection of native glycoRNAs

The current detection methods for glycoRNAs include metabolic labeling of living cells or animals and rPAL that directly detects native glycoRNAs by periodate oxidation and aldehyde ligation. Both of them have some limitations. Here we reported a simple and rapid detection of native glycoRNAs by using lectins. The method involves in several simple procedures: isolation of total RNA, northern blotting and detection with lectins. The advantages of this method include high sensitivity, very simple procedures and broader applications. We used this method detecting glycoRNA expression in the RNA samples from different species. We also detect the glycoRNA expression across the varieties of mouse and human tissues and compared with other detection methods. We are in the first to detect free glycoRNAs in the varieties of human biofluids. Overall, this simple and rapid method will provide a new tool for study of glycoRNA biology and clinical diagnosis in future.

biochemistry↗

bioRxiv2021

Direct activation of endothelial cells by SARS-CoV-2 nucleocapsid protein is blocked by Simvastatin

Emerging evidence suggests that endothelial activation plays a central role in the pathogenesis of acute respiratory distress syndrome (ARDS) and multi-organ failure in patients with COVID-19. However, the molecular mechanisms underlying endothelial activation in COVID-19 patients remain unclear. In this study, the SARS-CoV-2 viral proteins that potently activate human endothelial cells were screened to elucidate the molecular mechanisms involved with endothelial activation. It was found that nucleocapsid protein (NP) of SARS-CoV-2 significantly activated human endothelial cells through TLR2/NF-{kappa}B and MAPK signaling pathways. Moreover, by screening a natural microbial compound library containing 154 natural compounds, simvastatin was identified as a potent inhibitor of NP-induced endothelial activation. Remarkablely, though the protein sequences of N proteins from coronaviruses are highly conserved, only NP from SARS-CoV-2 induced endothelial activation. The NPs from other coronaviruses such as SARS-CoV, MERS-CoV, HUB1-CoV and influenza virus H1N1 did not affect endothelial activation. These findings are well consistent with the results from clinical investigations showing broad endotheliitis and organ injury in severe COVID-19 patients. In conclusion, the study provides insights on SARS-CoV-2-induced vasculopathy and coagulopathy, and suggests that simvastatin, an FDA-approved lipid-lowering drug, may benefit to prevent the pathogenesis and improve the outcome of COVID-19 patients.

immunology↗