P-selectin Facilitates SARS-CoV-2 Spike 1 Subunit Attachment to Vesicular Endothelium and Platelets

ACS Infect Dis. 2024 Jun 24. doi: 10.1021/acsinfecdis.3c00728.

Cheng Wang ¹, Shaobo Wang ², Xiangyu Ma ³, Xiaohong Yao ⁴, Kegang Zhan ³, Zai Wang ⁵, Di He ⁶ ⁷, Wenting Zuo ⁶ ⁸, Songling Han ¹, Gaomei Zhao ¹, Bin Cao ⁶ ⁷ ⁸ ⁹ ¹⁰ ¹¹, Jinghong Zhao ², Xiuwu Bian ⁴, Junping Wang ¹

Affiliations

1 State Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury of PLA, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing 400038, China.
2 Department of Nephrology, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing 400037, China.
3 Department of Epidemiology, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing 400038, China.
4 Institute of Pathology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China.
5 Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, China.
6 National Center for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing 100029, China.
7 Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Capital Medical University, Beijing 100069, China.
8 China-Japan Friendship Hospital (Institute of Clinical Medical Sciences), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.
9 Tsinghua University-Peking University Joint Center for Life Sciences, Beijing 100084, China.
10 Changping Laboratory, Beijing 102206, China.
11 New Cornerstone Science Laboratory, China-Japan Friendship Hospital, Beijing 100029, China.

PMID: 38912949 DOI: 10.1021/acsinfecdis.3c00728

Abstract

SARS-CoV-2 Infection starts from the association of its spike 1 (S1) subunit with sensitive cells. Vesicular endothelial cells and platelets are among the cell types that bind SARS-CoV-2, but the effectors that mediate viral attachment on the cell membrane have not been fully elucidated. Herein, we show that P-selectin (SELP), a biomarker for endothelial dysfunction and platelet activation, can facilitate the attachment of SARS-CoV-2 S1. Since we observe colocalization of SELP with S1 in the lung tissues of COVID-19 patients, we perform Molecular Biology experiments on human umbilical vein endothelial cells (HUVECs) to confirm the intermolecular interaction between SELP and S1. SELP overexpression increases S1 recruitment to HUVECs and enhances SARS-CoV-2 spike pseudovirion Infection. The opposite results are determined after SELP downregulation. As S1 causes endothelial inflammatory responses in a dose-dependent manner, by activating the interleukin (IL)-17 signaling pathway, SELP-induced S1 recruitment may contribute to the development of a "cytokine storm" after viral Infection. Furthermore, SELP also promotes the attachment of S1 to the platelet membrane. Employment of PSI-697, a small inhibitor of SELP, markedly decreases S1 adhesion to both HUVECs and platelets. In addition to the role of membrane SELP in facilitating S1 attachment, we also discover that soluble SELP is a prognostic factor for severe COVID-19 through a meta-analysis. In this study, we identify SELP as an adhesive site for the SARS-CoV-2 S1, thus providing a potential drug target for COVID-19 treatment.

Keywords

P-selectin; SARS-CoV-2; endothelium; platelet; spike.

Products

Cat. No.

Product Name

Description

Target

Research Area
HY-15526

PSI-697

99.73%, P-selectin Inhibitor

P-selectin

Cancer

Name
Email *

	Sorry, but the email address you supplied was invalid.