A pan-coronavirus fusion inhibitor targeting the HR1 domain of human coronavirus spike

Xia, Shuai; Yan, Lei; Xu, Wei; Agrawal, Anurodh Shankar; Algaissi, Abdullah; Tseng, Chien-Te K.; Wang, Qian; Du, Lanying; Tan, Wenjie; Wilson, Ian A.; Jiang, Shibo; Yang, Bei; Lu, Lu

Models for HR1(OC43)-L6-EK1, HR1(HKU1)-L6-EK1, and HR1(NL63)-L6-EK1 were derived by homology modeling using Swiss Model website (62) . The template for HR1(OC43)-L6-EK1 and HR1(HKU1)-L6-EK1 were obtained from the crystal structures of HR1(SARS)-L6-EK1 and HR1(MERS)-L6-EK1, and the template for HR1(NL63)-L6-EK1 proteins was obtained from the crystal structure of HR1(229E)-L6-EK1. To relax and stabilize the interaction between EK1 and corresponding HR1, initial models were optimized by performing energy minimization, followed by a 5-ns molecular dynamics simulation using Schrödinger Suite 2017-4 (www.schrodinger.com). The simulation systems were solvated with full-atom TIP3P water, containing Cl − and Na + ions at a concentration of 0.15 M to mimic physiological ionic strength. During the simulation, temperature T and pressure P were kept constant, at 310 K and 1 atm, respectively.