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The mechanisms underlying its pathogenicity in host organisms remain unclear. Animal models for studying the pathogenicity of SARS-CoV-2 proteins are lacking.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Using bioinformatic analysis, we found that 90% of the virus-host interactions involve human proteins conserved in\n                      <jats:italic>Drosophila<\/jats:italic>\n                      . Therefore, we generated a series of transgenic fly lines for individual SARS-CoV-2 genes, and used the Gal4-UAS system to express these viral genes in\n                      <jats:italic>Drosophila<\/jats:italic>\n                      to study their pathogenicity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We found that the ubiquitous expression of Orf6, Nsp6 or Orf7a in\n                      <jats:italic>Drosophila<\/jats:italic>\n                      led to reduced viability and tissue defects, including reduced trachea branching as well as muscle deficits resulting in a \u201cheld-up\u201d wing phenotype and poor climbing ability. Furthermore, muscles in these flies showed dramatically reduced mitochondria. Since Orf6 was found to interact with nucleopore proteins XPO1, we tested Selinexor, a drug that inhibits XPO1, and found that it could attenuate the Orf6-induced lethality and tissue-specific phenotypes\u00a0observed in flies.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our study established\n                      <jats:italic>Drosophila<\/jats:italic>\n                      as a model for studying the function of SARS-CoV2 genes, identified Orf6 as a highly pathogenic protein in various tissues, and demonstrated the potential of Selinexor for inhibiting Orf6 toxicity using an in vivo animal model system.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13578-021-00567-8","type":"journal-article","created":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T11:03:27Z","timestamp":1616670207000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Functional analysis of SARS-CoV-2 proteins in Drosophila identifies Orf6-induced pathogenic effects with Selinexor as an effective treatment"],"prefix":"10.1186","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4517-101X","authenticated-orcid":false,"given":"Jun-yi","family":"Zhu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9477-6990","authenticated-orcid":false,"given":"Jin-Gu","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1903-7295","authenticated-orcid":false,"given":"Joyce","family":"van de Leemput","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0442-8330","authenticated-orcid":false,"given":"Hangnoh","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5177-7798","authenticated-orcid":false,"given":"Zhe","family":"Han","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,3,25]]},"reference":[{"key":"567_CR1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00524-13","author":"MM Angelini","year":"2013","unstructured":"Angelini MM, Akhlaghpour M, Neuman BW, Buchmeier MJ. 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