PMC:7054935 / 3182-4596 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7054935","sourcedb":"PMC","sourceid":"7054935","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7054935","text":"It was proposed that the S gene from bat-derived CoV, unlike that from human patients- or civets-derived viruses, was unable to use human ACE2 as a receptor for entry into human cells [10,11]. Civets were proposed to be an intermediate host of the bat-CoVs, capable of spreading SARS CoV to humans [6,12]. However, in 2013 several novel bat coronaviruses were isolated from Chinese horseshoe bats and the bat SARS-like or SL-CoV-WIV1 was able to use ACE2 from humans, civets and Chinese horseshoe bats for entry [8]. Combined with evolutionary evidence that the bat ACE2 gene has been positively selected at the same contact sites as the human ACE2 gene for interacting with SARS CoV [13], it was proposed that an intermediate host may not be necessary and that some bat SL-CoVs may be able to directly infect human hosts. To directly address this possibility, the exact S gene from bat coronavirus SL-SHC014 was synthesized and used to generate a chimeric virus in the mouse adapted MA15 SARS-CoV backbone. The resultant SL-SHC014-MA15 virus could indeed efficiently use human ACE2 and replicate in primary human airway cells to similar titres as epidemic strains of SARS-CoV. While SL-SHC014-MA15 can replicate efficiently in young and aged mouse lungs, infection was attenuated, and less virus antigen was present in the airway epithelium as compared to SARS MA15, which causes lethal outcomes in aged mice 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