The SARS-CoV2 ORF7a protein has a conserved Ig immunoglobulin-like fold, which contains an integrin-binding site, providing a mechanistic hypothesis for the interaction between SARS-CoV2 and the human immune system . The SARS-COV ORF7a expressed in vitro causes apoptosis through a caspase-dependent pathway , inhibiting cell protein synthesis, and preventing cell cycle progression in G0/G1 phase , and activating NF-kB . It improves IL-8 promoter activity, activate of p38 MAP kinase . ORF7a protein is in the endoplasmic reticulum and Golgi apparatus of ORF7a cDNA transfected cells and SARS-CoV1 infected cells . ORF7a may trigger apoptosis by directly interfering with the pro-survival function of Bcl-X. The two proteins show co-localization in the plasma reticulum and mitochondria . Then SARS-CoV-2 ORF7a may reduce the functional mitochondria . SARS-CoV-2 ORF7a and SARS-CoV ORF7a have the same ER retention motif (KRKTE sequence), which indicates that SARS-CoV-2 ORF7a can be incorporated into the viral envelope as structure protein. It has involved ORF7a in immune regulation. But the truncation of the C-terminus negates the anti-immune activity of the protein, which leads to an increased response of type I interferons to viral infections . ORF7a polyubiquitination is mainly formed by K63-linked ubiquitin chains. Then ORF7a can inhibit type I interferon (IFN-I) signaling through STAT2 phosphorylation . In addition, ORF7a of SARS-CoV-2 interacts with ribosomal transporters HEATDR3 and MDN1 , and has been shown to inhibit cell translation in SARS-CoV .