@article{mbs:/content/journal/jgv/10.1099/jgv.0.001452, author = "Wang, Jingfang and Xu, Xintian and Zhou, Xinbo and Chen, Ping and Liang, Huiying and Li, Xuan and Zhong, Wu and Hao, Pei", title = "Molecular simulation of SARS-CoV-2 spike protein binding to pangolin ACE2 or human ACE2 natural variants reveals altered susceptibility to infection", journal= "Journal of General Virology", year = "2020", volume = "101", number = "9", pages = "921-924", doi = "https://doi.org/10.1099/jgv.0.001452", url = "https://www.microbiologyresearch.org/content/journal/jgv/10.1099/jgv.0.001452", publisher = "Microbiology Society", issn = "1465-2099", type = "Journal Article", keywords = "molecular dynamic simulation", keywords = "susceptibility", keywords = "SARS-CoV-2", keywords = "pangolin", keywords = "coronavirus", keywords = "ACE2 variants", abstract = "We constructed complex models of SARS-CoV-2 spike protein binding to pangolin or human ACE2, the receptor for virus transmission, and estimated the binding free energy changes using molecular dynamics simulation. SARS-CoV-2 can bind to both pangolin and human ACE2, but has a significantly lower binding affinity for pangolin ACE2 due to the increased binding free energy (9.5 kcal mol−1). Human ACE2 is among the most polymorphous genes, for which we identified 317 missense single-nucleotide variations (SNVs) from the dbSNP database. Three SNVs, E329G (rs143936283), M82I (rs267606406) and K26R (rs4646116), had a significant reduction in binding free energy, which indicated higher binding affinity than wild-type ACE2 and greater susceptibility to SARS-CoV-2 infection for people with them. Three other SNVs, D355N (rs961360700), E37K (rs146676783) and I21T (rs1244687367), had a significant increase in binding free energy, which indicated lower binding affinity and reduced susceptibility to SARS-CoV-2 infection.", }