{"doi":"10.1101/2020.06.05.136861","title":"Insights on cross-species transmission of SARS-CoV-2 from structural modeling","abstract":"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the ongoing global pandemic that has infected more than 14 million people in more than 180 countries worldwide. Like other coronaviruses, SARS-CoV-2 is thought to have been transmitted to humans from wild animals. Given the scale and widespread geographical distribution of the current pandemic, the question emerges whether human-to-animal transmission is possible and if so, which animal species are most at risk. Here, we investigated the structural properties of several ACE2 orthologs bound to the SARS-CoV-2 spike protein. We found that species known not to be susceptible to SARS-CoV-2 infection have non-conservative mutations in several ACE2 amino acid residues that disrupt key polar and charged contacts with the viral spike protein. Our models also predict affinity-enhancing mutations that could be used to design ACE2 variants for therapeutic purposes. Finally, our study provides a blueprint for modeling viral-host protein interactions and highlights several important considerations when designing these computational studies and analyzing their results.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":119717,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.95,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":314546,"name":"Susana Barrera-Vilarmau","orcid":"0000-0003-4868-6593","position":1,"is_corresponding":false},{"id":312379,"name":"João M. C. Teixeira","orcid":"0000-0002-9113-0622","position":2,"is_corresponding":false},{"id":314548,"name":"Elizabeth Seckel","orcid":"0000-0001-5910-649X","position":3,"is_corresponding":false},{"id":314549,"name":"Panagiotis L. Kastritis","orcid":"0000-0002-1463-8422","position":4,"is_corresponding":false},{"id":946,"name":"Michael Levitt","orcid":"0000-0002-8414-7397","position":5,"is_corresponding":false},{"id":314545,"name":"João Rodrigues","orcid":"0000-0001-9796-3193","position":0,"is_corresponding":true}],"reference_count":31,"raw_metadata":null,"created_at":"2026-07-18T23:14:13.002105Z","pmid":"32577636","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}