Wang et al. introduce a potential treatment for COVID-19 based on the fundamental characteristics of viral spike proteins and receptor binding. ACE2 is the well-known receptor of SARS-CoV-2 which allows it to enter the host cells. Wang et al. engineered membrane nanoparticles (ACE2-NPs) from ACE2-rich cells designed to suppress viral infection by competitive inhibition through binding the spike proteins of SARS-CoV-2. The ACE2-NPs demonstrated an inhibitory effect on the S1, which is a subunit of spike protein that recognizes the host receptors. Incubation of HK-2 human renal tubular epithelial cells with S1, with and without the presence of ACE2-NPs, showed a significant decrease in S1 receptor recruitment to cells. To test a more infectious case, an S1 variant was prepared by a single site mutation and resulted in a comparable affinity to ACE2 (11.6nM) compared to the wild-type S1 which has an affinity of (8.02nM). Also, ACE2-NPs treatment had a suppressive effect on the S1-induced apoptosis by increasing Optic atrophy 1 (OPA1) expression which is responsible for apoptosis by inhibiting the cytochrome c release. The antiviral activity of ACE2-NPs in various organs was verified using an in vivo mouse model—tracking the differently tagged ACE2 and S pseudovirions.