Emergence of SARS-CoV-2 through Recombination and Strong Purifying Selection

Xiaojun Li; Elena E. Giorgi; Manukumar Honnayakanahalli Marichann; Brian Foley; Chuan Xiao; Xiang-peng Kong; Yue Chen; Bette Korber; Feng Gao

To investigate the single mutation Q498H in RBM between SARS-CoV-2 and Pan_SL-CoV_GD, Q498 in the crystal structure of S/ACE2 complex was mutated to H498 using Chimera (44) . Local energy minimization (only H498 was allowed to move) was computed using Chimera's built-in functions. To investigate the impact of the deletion between residue 473 to 486 to the binding interface between SARS-CoV-2 and human ACE2, a homology model with the deletion was generated using I-TASSER (45) . The top five best models provided by the server have Confidence Score (C-score) of 0.86, -2.33, -4.01, -4.17, and -4.49. The C-score was used to estimate the quality of the models, which should be between -5.0 to 2; the higher the value, the higher the confidence in the model (45) . Based on the C-score, model 1 was used in Figure 2F . The interaction of the RBD of RaTG13 and ACE2 was modeled on PDB 6VW1, a hybrid structure of human SARS-CoV2 (46) using ICM software package (35) , and the mutational differences of the Gibbs free energy (Table S1) were calculated with the built-in algorithm. author/funder. All rights reserved. No reuse allowed without permission.