2021
Study on the promotion of lymphocytes in patients with COVID-19 by broad-spectrum chemokine receptor inhibitor vMIP-II and its Mechanism of signal transmission in vitro
Title:Study on the promotion of lymphocytes in patients with COVID-19 by broad-spectrum chemokine receptor inhibitor vMIP-II and its Mechanism of signal transmission in vitro
Author(s):Shiyu Li, Shuting Liu, Zhenyou Jiang, Lixia Feng, Yong Gao, Youyu Chen, Anding Xu, Wenhua Huang, Nuofu Zhang, Hanxiao Sun
Journal Name, Year, Volume(Issue):Signal Transduction and Targeted Therapy, 2021, 6: 104,Page range:1–4
DOI:10.1038/s41392-021-00516-4
Abstract:COVID-19 cases showed a significant decrease in the number of peripheral CD4⁺ and CD8⁺ T cells accompanied by overactivation of cells. HHV8-derived viral macrophage inflammatory protein vMIP-II is the only broad-spectrum chemokine receptor inhibitor that binds to three subtribes of chemokine receptors, which can significantly increase the specific cell immune response in infected organisms and have an effect of reducing plasma viral load on the viremia period. Here we report the effect of vMIP-II in COVID-19. This study included 10 patients and 35 uninfected patients. Lung CT scans before and 1 week after vMIP-II treatment showed significant alleviation of ground glass lesions and clinical symptoms. vMIP-II treatment significantly increased the total number and proportion of lymphocytes and shortened the time for the virus to turn negative. Mechanistic studies revealed that vMIP-II promotes the conversion of effector CD8⁺ T cells into central memory T cells (TCM) by inhibiting multiple chemokine receptors and the PI3K-AKT-mTOR signaling pathway, leading to mitochondrial dysfunction, metabolic shift toward glycolysis, and reduced methylase Dnmt3a activity. This study shows that vMIP-II can reconstruct the cellular immune function lost in acute SARS-CoV-2 infection, providing a new strategy for the treatment of COVID-19.
