Engineering mesenchymal stromal cells with neutralizing and anti-inflammatory capability against SARS-CoV-2 infection

Zhang, Xiaoqing; Han, Ping; Wang, Haiyong; Xu, Yanqin; Li, Fanlin; Li, Min; Fan, Lilv; Zhang, Huihui; Dai, Qiang; Lin, Hao; Qi, Xinyue; liang, Jie; Wang, Xin; Yang, Xuanming

The emergence of the novel human severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to the pandemic of coronavirus disease 2019 (COVID-19), which has markedly affected global health and economy. Both uncontrolled viral replication and proinflammatory cytokine storm can cause severe tissue damage in patients with COVID-19. SARS-CoV-2 utilizes angiotensin-converting enzyme 2 (ACE2) as its entry receptor. In this study, we generated ACE2 extracellular domain-Fc and scFv-IL6R-Fc fusion proteins to differentially neutralize viruses and ameliorate the cytokine storm. The hACE21-740-Fc fusion protein showed a potent inhibitory effect on pseudotyped SARS-CoV-2 entry and a good safety profile in mice. In addition, scFv-IL6R-Fc strongly blocked interleukin-6 signal activation. We also established a mesenchymal stromal cell MSC-based hACE21-740-Fc and scFv-IL6R-Fc delivery system, which could serve as a potential therapy strategy for urgent clinical needs of patients with COVID-19.