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10.1016/j.cell.2021.03.051 http://scihub22266oqcxt.onion/10.1016/j.cell.2021.03.051 33836156!8008343!33836156     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=33836156&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\33836156.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Cell 2021 ; 184 (10): 2618-2632.e17 Nephropedia Template TP {{tp|p=33836156|t=2021. TOP1 inhibition therapy protects against SARS-CoV-2-induced lethal inflammation |pdf=|usr=}}{{33836156}} gab.com Text TOP1 inhibition therapy protects against SARS-CoV-2-induced lethal inflammation JO: Cell http://www.kidney.de/pget.php?&tw=1&pmid=33836156 #FOAvip The ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently affecting millions of lives worldwide. Large retrospective studies indicate that an elevated level of inflammatory cytokines and pro-inflammatory factors are associated with both increased disease severity and mortality. Here, using multidimensional epigenetic, transcriptional, in vitro, and in vivo analyses, we report that topoisomerase 1 (TOP1) inhibition suppresses lethal inflammation induced by SARS-CoV-2. Therapeutic treatment with two doses of topotecan (TPT), an FDA-approved TOP1 inhibitor, suppresses infection-induced inflammation in hamsters. TPT treatment as late as 4 days post-infection reduces morbidity and rescues mortality in a transgenic mouse model. These results support the potential of TOP1 inhibition as an effective host-directed therapy against severe SARS-CoV-2 infection. TPT and its derivatives are inexpensive clinical-grade inhibitors available in most countries. Clinical trials are needed to evaluate the efficacy of repurposing TOP1 inhibitors for severe coronavirus disease 2019 (COVID-19) in humans. Twit Text FOAVip TOP1 inhibition therapy protects against SARS-CoV-2-induced lethal inflammation ????Cell http://www.kidney.de/pget.php?&tw=1&pmid=33836156 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=33836156 #FOAvip English Wikipedia <ref>{{Cite pmid|33836156}}</ref> TOP1 inhibition therapy protects against SARS-CoV-2-induced lethal inflammation #MMPMID33836156 Ho JSY; Mok BW; Campisi L; Jordan T; Yildiz S; Parameswaran S; Wayman JA; Gaudreault NN; Meekins DA; Indran SV; Morozov I; Trujillo JD; Fstkchyan YS; Rathnasinghe R; Zhu Z; Zheng S; Zhao N; White K; Ray-Jones H; Malysheva V; Thiecke MJ; Lau SY; Liu H; Zhang AJ; Lee AC; Liu WC; Jangra S; Escalera A; Aydillo T; Melo BS; Guccione E; Sebra R; Shum E; Bakker J; Kaufman DA; Moreira AL; Carossino M; Balasuriya UBR; Byun M; Albrecht RA; Schotsaert M; Garcia-Sastre A; Chanda SK; Miraldi ER; Jeyasekharan AD; TenOever BR; Spivakov M; Weirauch MT; Heinz S; Chen H; Benner C; Richt JA; Marazzi I Cell 2021[May]; 184 (10): 2618-2632.e17 PMID33836156show ga The ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently affecting millions of lives worldwide. Large retrospective studies indicate that an elevated level of inflammatory cytokines and pro-inflammatory factors are associated with both increased disease severity and mortality. Here, using multidimensional epigenetic, transcriptional, in vitro, and in vivo analyses, we report that topoisomerase 1 (TOP1) inhibition suppresses lethal inflammation induced by SARS-CoV-2. Therapeutic treatment with two doses of topotecan (TPT), an FDA-approved TOP1 inhibitor, suppresses infection-induced inflammation in hamsters. TPT treatment as late as 4 days post-infection reduces morbidity and rescues mortality in a transgenic mouse model. These results support the potential of TOP1 inhibition as an effective host-directed therapy against severe SARS-CoV-2 infection. TPT and its derivatives are inexpensive clinical-grade inhibitors available in most countries. Clinical trials are needed to evaluate the efficacy of repurposing TOP1 inhibitors for severe coronavirus disease 2019 (COVID-19) in humans. |*COVID-19 Drug Treatment[MESH] |Animals[MESH] |COVID-19/enzymology/pathology[MESH] |Chlorocebus aethiops[MESH] |DNA Topoisomerases, Type I/*metabolism[MESH] |Humans[MESH] |Inflammation/drug therapy/enzymology/pathology/virology[MESH] |Mesocricetus[MESH] |Mice[MESH] |Mice, Transgenic[MESH] |SARS-CoV-2/*metabolism[MESH] |THP-1 Cells[MESH] |Topoisomerase I Inhibitors/*pharmacology[MESH] |Topotecan/*pharmacology[MESH]TOP1 inhibition therapy protects against SARS-CoV-2-induced lethal inf(epmc).pdf DeepDyve Pubget Overpricing