Engineering mesenchymal stem cells with neutralizing and anti- inflammation dual-capability against SARS-CoV-2 infection

Abstract The emergence of the novel human coronavirus SARS-CoV-2 has caused a worldwide epidemic of coronavirus disease 2019 (COVID-19), which markedly affected the global health and economy. Both uncontrolled viral replication and proinflammatory cytokine storm can cause severe tissue damage in COVID-19 patients. 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 protein to differentially neutralize virus and temper cytokine storm. The hACE21-740-Fc fusion protein showed potent inhibitory effect on pseudotyped SARS-CoV-2 entry and good safety profile in mice. The scFv-IL6R-Fc showed strong blockade effect on IL-6 signal activation. In addition, we established a mesenchymal stem cells (MSCs)-based hACE21-740-Fc and scFv-IL6R-Fc delivery strategy, which provided a potential rapid option for urgent clinic therapeutic need of COVID-19 patients.