tetano
Editor, Senior Moderator
Nature
. 2021 Feb 9.
doi: 10.1038/s41586-021-03312-w. Online ahead of print.
SARS-CoV-2 infection is effectively treated and prevented by EIDD-2801
Angela Wahl[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Lisa E Gralinski[SUP] #[/SUP][SUP] 4 [/SUP], Claire E Johnson[SUP] 1 2 3 [/SUP], Wenbo Yao[SUP] 1 2 3 [/SUP], Martina Kovarova[SUP] 1 2 3 [/SUP], Kenneth H Dinnon 3rd[SUP] 4 5 [/SUP], Hongwei Liu[SUP] 6 7 [/SUP], Victoria J Madden[SUP] 8 [/SUP], Halina M Krzystek[SUP] 6 7 [/SUP], Chandrav De[SUP] 1 2 3 [/SUP], Kristen K White[SUP] 8 [/SUP], Kendra Gully[SUP] 4 [/SUP], Alexandra Sch?fer[SUP] 4 [/SUP], Tanzila Zaman[SUP] 6 7 [/SUP], Sarah R Leist[SUP] 4 [/SUP], Paul O Grant[SUP] 6 7 [/SUP], Gregory R Bluemling[SUP] 9 10 [/SUP], Alexander A Kolykhalov[SUP] 9 10 [/SUP], Michael G Natchus[SUP] 10 [/SUP], Frederic B Askin[SUP] 11 [/SUP], George Painter[SUP] 9 10 12 [/SUP], Edward P Browne[SUP] 2 3 5 13 [/SUP], Corbin D Jones[SUP] 6 7 [/SUP], Raymond J Pickles[SUP] 5 14 [/SUP], Ralph S Baric[SUP] 4 5 15 [/SUP], J Victor Garcia[SUP] 16 17 18 [/SUP]
Affiliations
Abstract
All known recently emerged human coronaviruses probably originated in bats[SUP]1[/SUP]. Here we used a single experimental platform based on human lung-only mice (LoM) to demonstrate efficient in vivo replication of all recently emerged human coronaviruses (SARS-CoV, MERS-CoV and SARS-CoV-2) and two highly relevant endogenous pre-pandemic SARS-like bat coronaviruses. Virus replication in this model occurs in bona fide human lung tissue and does not require any type of adaptation of the virus or the host. Our results indicate that bats harbour endogenous coronaviruses capable of direct transmission into humans. Further detailed analysis of pandemic SARS-CoV-2 in vivo infection of LoM human lung tissue showed predominant infection of human lung epithelial cells, including type II pneumocytes present in alveoli and ciliated airway cells. Acute SARS-CoV-2 infection was highly cytopathic and induced a robust and sustained type I interferon and inflammatory cytokine/chemokine response. Finally, we evaluated a therapeutic and pre-exposure prophylaxis strategy for coronavirus infection. Our results show that therapeutic and prophylactic administration of EIDD-2801, an oral broad spectrum antiviral currently in phase II-III clinical trials, dramatically inhibited SARS-CoV-2 replication in vivo and thus has significant potential for the prevention and treatment of COVID-19.
. 2021 Feb 9.
doi: 10.1038/s41586-021-03312-w. Online ahead of print.
SARS-CoV-2 infection is effectively treated and prevented by EIDD-2801
Angela Wahl[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Lisa E Gralinski[SUP] #[/SUP][SUP] 4 [/SUP], Claire E Johnson[SUP] 1 2 3 [/SUP], Wenbo Yao[SUP] 1 2 3 [/SUP], Martina Kovarova[SUP] 1 2 3 [/SUP], Kenneth H Dinnon 3rd[SUP] 4 5 [/SUP], Hongwei Liu[SUP] 6 7 [/SUP], Victoria J Madden[SUP] 8 [/SUP], Halina M Krzystek[SUP] 6 7 [/SUP], Chandrav De[SUP] 1 2 3 [/SUP], Kristen K White[SUP] 8 [/SUP], Kendra Gully[SUP] 4 [/SUP], Alexandra Sch?fer[SUP] 4 [/SUP], Tanzila Zaman[SUP] 6 7 [/SUP], Sarah R Leist[SUP] 4 [/SUP], Paul O Grant[SUP] 6 7 [/SUP], Gregory R Bluemling[SUP] 9 10 [/SUP], Alexander A Kolykhalov[SUP] 9 10 [/SUP], Michael G Natchus[SUP] 10 [/SUP], Frederic B Askin[SUP] 11 [/SUP], George Painter[SUP] 9 10 12 [/SUP], Edward P Browne[SUP] 2 3 5 13 [/SUP], Corbin D Jones[SUP] 6 7 [/SUP], Raymond J Pickles[SUP] 5 14 [/SUP], Ralph S Baric[SUP] 4 5 15 [/SUP], J Victor Garcia[SUP] 16 17 18 [/SUP]
Affiliations
- PMID: 33561864
- DOI: 10.1038/s41586-021-03312-w
Abstract
All known recently emerged human coronaviruses probably originated in bats[SUP]1[/SUP]. Here we used a single experimental platform based on human lung-only mice (LoM) to demonstrate efficient in vivo replication of all recently emerged human coronaviruses (SARS-CoV, MERS-CoV and SARS-CoV-2) and two highly relevant endogenous pre-pandemic SARS-like bat coronaviruses. Virus replication in this model occurs in bona fide human lung tissue and does not require any type of adaptation of the virus or the host. Our results indicate that bats harbour endogenous coronaviruses capable of direct transmission into humans. Further detailed analysis of pandemic SARS-CoV-2 in vivo infection of LoM human lung tissue showed predominant infection of human lung epithelial cells, including type II pneumocytes present in alveoli and ciliated airway cells. Acute SARS-CoV-2 infection was highly cytopathic and induced a robust and sustained type I interferon and inflammatory cytokine/chemokine response. Finally, we evaluated a therapeutic and pre-exposure prophylaxis strategy for coronavirus infection. Our results show that therapeutic and prophylactic administration of EIDD-2801, an oral broad spectrum antiviral currently in phase II-III clinical trials, dramatically inhibited SARS-CoV-2 replication in vivo and thus has significant potential for the prevention and treatment of COVID-19.