Lectin-like Intestinal Defensin Inhibits 2019-nCoV Spike binding to ACE2

Cheng Wang; Shaobo Wang; Daixi Li; Xia Zhao; Songling Han; Tao Wang; Gaomei Zhao; Yin Chen; Fang Chen; Jianqi Zhao; Liting Wang; Wei Sun; Yi Huang; Yongping Su; Dongqing Wei; Jinghong Zhao; Junping Wang

Coronavirus owns enveloped positive-stranded RNA encoding the spike (S) protein, envelope protein, membrane protein, and nucleoprotein. S protein is composed of 1160-1400 amino acids and presents as a trimer before membrane fusion 6 . Many S proteins can be divided into S1 and S2 subunits after degradation by protease 7 . The S1 subunit contains a receptor-binding domain (RBD) and devotes to the initial viral attachment via recognizing a variety of host cell receptors, including aminopeptidase N (APN), angiotensin-converting enzyme-2 (ACE2), dipeptidyl peptidase 4 (DPP4), carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), and sugar 8, 9, 10 . Since the sequence of 2019-nCoV S protein is 76.47% homology to that of SARS-CoV 11 , ACE2, which is identified as the crucial target for SARS-CoV, was also considered the host receptor of 2019-nCoV 12 . In fact, it was reported that host cells expressed ACE2, instead of APN and DPP4, were sensitive to 2019-nCoV 13, 14 . In vitro binding assay demonstrated that ACE2 enabled a potent interaction with 2019-nCoV S protein with an affinity of 14.7 nM 15 , which is 10-to 20-fold higher than that of ACE2 binding to SARS-CoV S protein.