7ci3

Publication Abstract from PubMed

Dysregulated immune cell responses have been linked to the severity of coronavirus disease 2019 (COVID-19), but the specific viral factors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were currently unknown. Herein, we reveal that the Immunoglobulin-like fold ectodomain of the viral protein SARS-CoV-2 ORF7a interacts with high efficiency to CD14(+) monocytes in human peripheral blood, compared to pathogenic protein SARS-CoV ORF7a. The crystal structure of SARS-CoV-2 ORF7a at 2.2 A resolution reveals three remarkable changes on the amphipathic side of the four-stranded beta-sheet, implying a potential functional interface of the viral protein. Importantly, SARS-CoV-2 ORF7a coincubation with CD14(+) monocytes ex vivo triggered a decrease in HLA-DR/DP/DQ expression levels and upregulated significant production of proinflammatory cytokines, including IL-6, IL-1beta, IL-8, and TNF-alpha. Our work demonstrates that SARS-CoV-2 ORF7a is an immunomodulating factor for immune cell binding and triggers dramatic inflammatory responses, providing promising therapeutic drug targets for pandemic COVID-19.

Structural insight reveals SARS-CoV-2 ORF7a as an immunomodulating factor for human CD14(+) monocytes.,Zhou Z, Huang C, Zhou Z, Huang Z, Su L, Kang S, Chen X, Chen Q, He S, Rong X, Xiao F, Chen J, Chen S iScience. 2021 Mar 19;24(3):102187. doi: 10.1016/j.isci.2021.102187. Epub 2021, Feb 12. PMID:33615195^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.