Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2

Abstract Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles,...
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Autor*in:	Rui Xiong [verfasserIn] Leike Zhang [verfasserIn] Shiliang Li [verfasserIn] Yuan Sun [verfasserIn] Minyi Ding [verfasserIn] Yong Wang [verfasserIn] Yongliang Zhao [verfasserIn] Yan Wu [verfasserIn] Weijuan Shang [verfasserIn] Xiaming Jiang [verfasserIn] Jiwei Shan [verfasserIn] Zihao Shen [verfasserIn] Yi Tong [verfasserIn] Liuxin Xu [verfasserIn] Yu Chen [verfasserIn] Yingle Liu [verfasserIn] Gang Zou [verfasserIn] Dimitri Lavillete [verfasserIn] Zhenjiang Zhao [verfasserIn] Rui Wang [verfasserIn] Lili Zhu [verfasserIn] Gengfu Xiao [verfasserIn] Ke Lan [verfasserIn] Honglin Li [verfasserIn] Ke Xu [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2020

Schlagwörter:	de novo pyrimidine biosynthesis DHODH inhibitors SARS-CoV-2 influenza viruses virus replication immuno-regulation

Übergeordnetes Werk:	In: Protein & Cell - Oxford University Press, 2016, 11(2020), 10, Seite 723-739
Übergeordnetes Werk:	volume:11 ; year:2020 ; number:10 ; pages:723-739

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc Journal toc

DOI / URN:	10.1007/s13238-020-00768-w

Katalog-ID:	DOAJ049327933

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520			\|a Abstract Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC50 of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.
650		4	\|a de novo pyrimidine biosynthesis
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653		0	\|a Cytology
653		0	\|a Animal biochemistry
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700	0		\|a Ke Xu \|e verfasserin \|4 aut
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allfields	10.1007/s13238-020-00768-w doi (DE-627)DOAJ049327933 (DE-599)DOAJ7cc08278afd440c58f310a8ae77636f7 DE-627 ger DE-627 rakwb eng QH573-671 QP501-801 Rui Xiong verfasserin aut Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC50 of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not. de novo pyrimidine biosynthesis DHODH inhibitors SARS-CoV-2 influenza viruses virus replication immuno-regulation Cytology Animal biochemistry Leike Zhang verfasserin aut Shiliang Li verfasserin aut Yuan Sun verfasserin aut Minyi Ding verfasserin aut Yong Wang verfasserin aut Yongliang Zhao verfasserin aut Yan Wu verfasserin aut Weijuan Shang verfasserin aut Xiaming Jiang verfasserin aut Jiwei Shan verfasserin aut Zihao Shen verfasserin aut Yi Tong verfasserin aut Liuxin Xu verfasserin aut Yu Chen verfasserin aut Yingle Liu verfasserin aut Gang Zou verfasserin aut Dimitri Lavillete verfasserin aut Zhenjiang Zhao verfasserin aut Rui Wang verfasserin aut Lili Zhu verfasserin aut Gengfu Xiao verfasserin aut Ke Lan verfasserin aut Honglin Li verfasserin aut Ke Xu verfasserin aut In Protein & Cell Oxford University Press, 2016 11(2020), 10, Seite 723-739 (DE-627)621548308 (DE-600)2543451-2 16748018 nnns volume:11 year:2020 number:10 pages:723-739 https://doi.org/10.1007/s13238-020-00768-w kostenfrei https://doaj.org/article/7cc08278afd440c58f310a8ae77636f7 kostenfrei https://doi.org/10.1007/s13238-020-00768-w kostenfrei https://doaj.org/toc/1674-800X Journal toc kostenfrei https://doaj.org/toc/1674-8018 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2020 10 723-739
spelling	10.1007/s13238-020-00768-w doi (DE-627)DOAJ049327933 (DE-599)DOAJ7cc08278afd440c58f310a8ae77636f7 DE-627 ger DE-627 rakwb eng QH573-671 QP501-801 Rui Xiong verfasserin aut Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC50 of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not. de novo pyrimidine biosynthesis DHODH inhibitors SARS-CoV-2 influenza viruses virus replication immuno-regulation Cytology Animal biochemistry Leike Zhang verfasserin aut Shiliang Li verfasserin aut Yuan Sun verfasserin aut Minyi Ding verfasserin aut Yong Wang verfasserin aut Yongliang Zhao verfasserin aut Yan Wu verfasserin aut Weijuan Shang verfasserin aut Xiaming Jiang verfasserin aut Jiwei Shan verfasserin aut Zihao Shen verfasserin aut Yi Tong verfasserin aut Liuxin Xu verfasserin aut Yu Chen verfasserin aut Yingle Liu verfasserin aut Gang Zou verfasserin aut Dimitri Lavillete verfasserin aut Zhenjiang Zhao verfasserin aut Rui Wang verfasserin aut Lili Zhu verfasserin aut Gengfu Xiao verfasserin aut Ke Lan verfasserin aut Honglin Li verfasserin aut Ke Xu verfasserin aut In Protein & Cell Oxford University Press, 2016 11(2020), 10, Seite 723-739 (DE-627)621548308 (DE-600)2543451-2 16748018 nnns volume:11 year:2020 number:10 pages:723-739 https://doi.org/10.1007/s13238-020-00768-w kostenfrei https://doaj.org/article/7cc08278afd440c58f310a8ae77636f7 kostenfrei https://doi.org/10.1007/s13238-020-00768-w kostenfrei https://doaj.org/toc/1674-800X Journal toc kostenfrei https://doaj.org/toc/1674-8018 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2020 10 723-739
allfields_unstemmed	10.1007/s13238-020-00768-w doi (DE-627)DOAJ049327933 (DE-599)DOAJ7cc08278afd440c58f310a8ae77636f7 DE-627 ger DE-627 rakwb eng QH573-671 QP501-801 Rui Xiong verfasserin aut Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC50 of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not. de novo pyrimidine biosynthesis DHODH inhibitors SARS-CoV-2 influenza viruses virus replication immuno-regulation Cytology Animal biochemistry Leike Zhang verfasserin aut Shiliang Li verfasserin aut Yuan Sun verfasserin aut Minyi Ding verfasserin aut Yong Wang verfasserin aut Yongliang Zhao verfasserin aut Yan Wu verfasserin aut Weijuan Shang verfasserin aut Xiaming Jiang verfasserin aut Jiwei Shan verfasserin aut Zihao Shen verfasserin aut Yi Tong verfasserin aut Liuxin Xu verfasserin aut Yu Chen verfasserin aut Yingle Liu verfasserin aut Gang Zou verfasserin aut Dimitri Lavillete verfasserin aut Zhenjiang Zhao verfasserin aut Rui Wang verfasserin aut Lili Zhu verfasserin aut Gengfu Xiao verfasserin aut Ke Lan verfasserin aut Honglin Li verfasserin aut Ke Xu verfasserin aut In Protein & Cell Oxford University Press, 2016 11(2020), 10, Seite 723-739 (DE-627)621548308 (DE-600)2543451-2 16748018 nnns volume:11 year:2020 number:10 pages:723-739 https://doi.org/10.1007/s13238-020-00768-w kostenfrei https://doaj.org/article/7cc08278afd440c58f310a8ae77636f7 kostenfrei https://doi.org/10.1007/s13238-020-00768-w kostenfrei https://doaj.org/toc/1674-800X Journal toc kostenfrei https://doaj.org/toc/1674-8018 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2020 10 723-739
allfieldsGer	10.1007/s13238-020-00768-w doi (DE-627)DOAJ049327933 (DE-599)DOAJ7cc08278afd440c58f310a8ae77636f7 DE-627 ger DE-627 rakwb eng QH573-671 QP501-801 Rui Xiong verfasserin aut Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC50 of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not. de novo pyrimidine biosynthesis DHODH inhibitors SARS-CoV-2 influenza viruses virus replication immuno-regulation Cytology Animal biochemistry Leike Zhang verfasserin aut Shiliang Li verfasserin aut Yuan Sun verfasserin aut Minyi Ding verfasserin aut Yong Wang verfasserin aut Yongliang Zhao verfasserin aut Yan Wu verfasserin aut Weijuan Shang verfasserin aut Xiaming Jiang verfasserin aut Jiwei Shan verfasserin aut Zihao Shen verfasserin aut Yi Tong verfasserin aut Liuxin Xu verfasserin aut Yu Chen verfasserin aut Yingle Liu verfasserin aut Gang Zou verfasserin aut Dimitri Lavillete verfasserin aut Zhenjiang Zhao verfasserin aut Rui Wang verfasserin aut Lili Zhu verfasserin aut Gengfu Xiao verfasserin aut Ke Lan verfasserin aut Honglin Li verfasserin aut Ke Xu verfasserin aut In Protein & Cell Oxford University Press, 2016 11(2020), 10, Seite 723-739 (DE-627)621548308 (DE-600)2543451-2 16748018 nnns volume:11 year:2020 number:10 pages:723-739 https://doi.org/10.1007/s13238-020-00768-w kostenfrei https://doaj.org/article/7cc08278afd440c58f310a8ae77636f7 kostenfrei https://doi.org/10.1007/s13238-020-00768-w kostenfrei https://doaj.org/toc/1674-800X Journal toc kostenfrei https://doaj.org/toc/1674-8018 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2020 10 723-739
allfieldsSound	10.1007/s13238-020-00768-w doi (DE-627)DOAJ049327933 (DE-599)DOAJ7cc08278afd440c58f310a8ae77636f7 DE-627 ger DE-627 rakwb eng QH573-671 QP501-801 Rui Xiong verfasserin aut Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC50 of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not. de novo pyrimidine biosynthesis DHODH inhibitors SARS-CoV-2 influenza viruses virus replication immuno-regulation Cytology Animal biochemistry Leike Zhang verfasserin aut Shiliang Li verfasserin aut Yuan Sun verfasserin aut Minyi Ding verfasserin aut Yong Wang verfasserin aut Yongliang Zhao verfasserin aut Yan Wu verfasserin aut Weijuan Shang verfasserin aut Xiaming Jiang verfasserin aut Jiwei Shan verfasserin aut Zihao Shen verfasserin aut Yi Tong verfasserin aut Liuxin Xu verfasserin aut Yu Chen verfasserin aut Yingle Liu verfasserin aut Gang Zou verfasserin aut Dimitri Lavillete verfasserin aut Zhenjiang Zhao verfasserin aut Rui Wang verfasserin aut Lili Zhu verfasserin aut Gengfu Xiao verfasserin aut Ke Lan verfasserin aut Honglin Li verfasserin aut Ke Xu verfasserin aut In Protein & Cell Oxford University Press, 2016 11(2020), 10, Seite 723-739 (DE-627)621548308 (DE-600)2543451-2 16748018 nnns volume:11 year:2020 number:10 pages:723-739 https://doi.org/10.1007/s13238-020-00768-w kostenfrei https://doaj.org/article/7cc08278afd440c58f310a8ae77636f7 kostenfrei https://doi.org/10.1007/s13238-020-00768-w kostenfrei https://doaj.org/toc/1674-800X Journal toc kostenfrei https://doaj.org/toc/1674-8018 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2020 10 723-739
language	English
source	In Protein & Cell 11(2020), 10, Seite 723-739 volume:11 year:2020 number:10 pages:723-739
sourceStr	In Protein & Cell 11(2020), 10, Seite 723-739 volume:11 year:2020 number:10 pages:723-739
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	de novo pyrimidine biosynthesis DHODH inhibitors SARS-CoV-2 influenza viruses virus replication immuno-regulation Cytology Animal biochemistry
isfreeaccess_bool	true
container_title	Protein & Cell
authorswithroles_txt_mv	Rui Xiong @@aut@@ Leike Zhang @@aut@@ Shiliang Li @@aut@@ Yuan Sun @@aut@@ Minyi Ding @@aut@@ Yong Wang @@aut@@ Yongliang Zhao @@aut@@ Yan Wu @@aut@@ Weijuan Shang @@aut@@ Xiaming Jiang @@aut@@ Jiwei Shan @@aut@@ Zihao Shen @@aut@@ Yi Tong @@aut@@ Liuxin Xu @@aut@@ Yu Chen @@aut@@ Yingle Liu @@aut@@ Gang Zou @@aut@@ Dimitri Lavillete @@aut@@ Zhenjiang Zhao @@aut@@ Rui Wang @@aut@@ Lili Zhu @@aut@@ Gengfu Xiao @@aut@@ Ke Lan @@aut@@ Honglin Li @@aut@@ Ke Xu @@aut@@
publishDateDaySort_date	2020-01-01T00:00:00Z
hierarchy_top_id	621548308
id	DOAJ049327933
language_de	englisch
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callnumber-first	Q - Science
author	Rui Xiong
spellingShingle	Rui Xiong misc QH573-671 misc QP501-801 misc de novo pyrimidine biosynthesis misc DHODH inhibitors misc SARS-CoV-2 misc influenza viruses misc virus replication misc immuno-regulation misc Cytology misc Animal biochemistry Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2
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topic_title	QH573-671 QP501-801 Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2 de novo pyrimidine biosynthesis DHODH inhibitors SARS-CoV-2 influenza viruses virus replication immuno-regulation
topic	misc QH573-671 misc QP501-801 misc de novo pyrimidine biosynthesis misc DHODH inhibitors misc SARS-CoV-2 misc influenza viruses misc virus replication misc immuno-regulation misc Cytology misc Animal biochemistry
topic_unstemmed	misc QH573-671 misc QP501-801 misc de novo pyrimidine biosynthesis misc DHODH inhibitors misc SARS-CoV-2 misc influenza viruses misc virus replication misc immuno-regulation misc Cytology misc Animal biochemistry
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title	Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2
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title_full	Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2
author_sort	Rui Xiong
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author_browse	Rui Xiong Leike Zhang Shiliang Li Yuan Sun Minyi Ding Yong Wang Yongliang Zhao Yan Wu Weijuan Shang Xiaming Jiang Jiwei Shan Zihao Shen Yi Tong Liuxin Xu Yu Chen Yingle Liu Gang Zou Dimitri Lavillete Zhenjiang Zhao Rui Wang Lili Zhu Gengfu Xiao Ke Lan Honglin Li Ke Xu
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title_sort	novel and potent inhibitors targeting dhodh are broad-spectrum antivirals against rna viruses including newly-emerged coronavirus sars-cov-2
callnumber	QH573-671
title_auth	Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2
abstract	Abstract Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC50 of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.
abstractGer	Abstract Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC50 of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.
abstract_unstemmed	Abstract Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC50 of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.
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title_short	Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2
url	https://doi.org/10.1007/s13238-020-00768-w https://doaj.org/article/7cc08278afd440c58f310a8ae77636f7 https://doaj.org/toc/1674-800X https://doaj.org/toc/1674-8018
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author2	Leike Zhang Shiliang Li Yuan Sun Minyi Ding Yong Wang Yongliang Zhao Yan Wu Weijuan Shang Xiaming Jiang Jiwei Shan Zihao Shen Yi Tong Liuxin Xu Yu Chen Yingle Liu Gang Zou Dimitri Lavillete Zhenjiang Zhao Rui Wang Lili Zhu Gengfu Xiao Ke Lan Honglin Li Ke Xu
author2Str	Leike Zhang Shiliang Li Yuan Sun Minyi Ding Yong Wang Yongliang Zhao Yan Wu Weijuan Shang Xiaming Jiang Jiwei Shan Zihao Shen Yi Tong Liuxin Xu Yu Chen Yingle Liu Gang Zou Dimitri Lavillete Zhenjiang Zhao Rui Wang Lili Zhu Gengfu Xiao Ke Lan Honglin Li Ke Xu
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up_date	2024-07-03T22:45:32.557Z
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