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{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7643666","sourcedb":"PMC","sourceid":"7643666","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7643666","text":"4 Discussion\nItaly is among the European countries the wealthiest for biodiversity [17]. (https://www.isprambiente.gov.it/en/archive/news-and-other-events/ispra-news/year-2015/may/biodiversity-in-italy). As mammal biodiversity has been recognized as risk factor for zoonotic disease emergence, the Italian region is exposed to a high risk of SARS-CoV-2 pandemic outbreak and the relative risk of endangered animal extinction.\nAs a great deal of evidence indicates that SARS-CoV-2 originated from the bat, the present work aimed to identify the Chiroptera species living in Italy that could be the primary reservoir in this region.\nAccordingly, performing in silico calculation based on multiple sequence alignment and homology modeling, molecular docking, and molecular dynamics, we identified Rhinolophus ferrumequinum as the best Chiroptera candidate to be the potential primary reservoir for the SARS-CoV-2 virus in Italy. The sequence alignment of Rhinolophus ferrumequinum ACE2 with hACE2 sequence indicated that most of the residues involved in SARS-CoV-2 S binding are conserved. Moreover, Rhinolophus ferrumequinum ACE2 shows the highest identity with the ACE2 proteins of wild and domestic species present in Italy (Figure 3B), indicating a potential role as a human-animals bridge infection in wild and domestic environments.\nA low number of domestic animals have been found infected by SARS-CoV-2, despite the high viral circulation during the current pandemic. This may depend on a still inadequate screening of domestic animals or a low human-to-animals transmission rate in natural conditions. The low transmission rate might depend on an innate or acquired resistance of domestic animals to the virus or in the differences in the structure of ACE2 proteins.\nOur data show that a conserved pattern of residues is present in ACE2 proteins of many animal species, in particular horses (Equus caballus), cats (Felis catus), cattle (Bos taurus), and sheep (Ovis aries), among the domestic animals, European rabbits (Oryctolagus cuniculus) and grizzly bear (Ursus arctos horribilis) among the wild animals. Considering these data, animal species present in Italy could be considered SARS-CoV-2 secondary reservoirs, or else could behave as host intermediate if infected by bat coronaviruses. On the contrary, ACE2 proteins of animals like dogs (Canis lupus familiaris) and red fox (Vulpes vulpes) that do not exhibit this residue pattern, are not eligible as SARS-CoV-2 host intermediates. These results agree with recently published data that exclude pigs as infection transmitters and recognize dogs as low susceptible to the experimental infection [6]. On the other hand, cats (and other animals) may be a silent intermediate host of SARS-CoV-2, because infected cats have never shown any visible symptoms that might be recognized by their owners [10]. The high conservation rate of ACE2 residues may suggest that also farm animals such as cattle and sheep may be endangered by a viral transmission, and finally, the horse can be a potential intermediate host transmitting SARS-CoV-2 to humans.\nTaken together, our data point to Rhinolophus ferrumequinum as a potential primary reservoir for SARS-CoV-2 in Italy, and domestic and wild animal species can act as the second reservoir. However, the similarity of ACE2/spike protein complexes among these species does not explain the low human-to-animals transmission rate of SARS-CoV-2 infection. An innate or acquired resistance of domestic animals to the virus potentially accounts for the rare infection of domestic or wild animals occurring during the pandemic.","divisions":[{"label":"label","span":{"begin":0,"end":1}},{"label":"title","span":{"begin":3,"end":13}},{"label":"p","span":{"begin":14,"end":426}},{"label":"p","span":{"begin":427,"end":631}},{"label":"p","span":{"begin":632,"end":1336}},{"label":"p","span":{"begin":1337,"end":1773}},{"label":"p","span":{"begin":1774,"end":3107}}],"tracks":[{"project":"Zoonoses","denotations":[{"id":"T18","span":{"begin":1052,"end":1064},"obj":"Gene"}],"attributes":[{"id":"A18","pred":"tao:has_database_id","subj":"T18","obj":"Gene:43740568"},{"subj":"T18","pred":"source","obj":"Zoonoses"}]},{"project":"Covid19_manual_annotation_v2","denotations":[{"id":"T18","span":{"begin":1052,"end":1064},"obj":"Gene"}],"attributes":[{"id":"A18","pred":"tao:has_database_id","subj":"T18","obj":"Gene:43740568"},{"subj":"T18","pred":"source","obj":"Covid19_manual_annotation_v2"}],"namespaces":[{"prefix":"Tax","uri":"https://www.ncbi.nlm.nih.gov/taxonomy/"},{"prefix":"MESH","uri":"https://id.nlm.nih.gov/mesh/"},{"prefix":"Gene","uri":"https://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"BioProject","uri":"https://www.ncbi.nlm.nih.gov/bioproject/"},{"prefix":"CVCL","uri":"https://web.expasy.org/cellosaurus/CVCL_"},{"prefix":"HP","uri":"https://hpo.jax.org/app/browse/term/HP:"},{"prefix":"BioSample","uri":"https://www.ncbi.nlm.nih.gov/biosample/"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"Zoonoses","color":"#c8ec93","default":true},{"id":"Covid19_manual_annotation_v2","color":"#ec93e2"}]}]}}