SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor
Markus Hoffmann,Hannah Kleine-Weber,Simon Schroeder,Nadine Krüger,Tanja Herrler,Sandra Erichsen,Tobias S. Schiergens,Georg Herrler,Nai Huei Wu,Andreas Nitsche,Marcel A. Müller,Christian Drosten,Christian Drosten,Stefan Pöhlmann +13 more
TLDR
It is demonstrated that SARS-CoV-2 uses the SARS -CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming, and it is shown that the sera from convalescent SARS patients cross-neutralized Sars-2-S-driven entry.About:
This article is published in Cell.The article was published on 2020-04-16 and is currently open access. It has received 15362 citations till now. The article focuses on the topics: Proteases.read more
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Spike mutation D614G alters SARS-CoV-2 fitness and neutralization susceptibility.
Jessica A. Plante,Yang Liu,Jianying Liu,Hongjie Xia,Bryan A. Johnson,Kumari G. Lokugamage,Xianwen Zhang,Antonio E. Muruato,Jing Zou,Camila R. Fontes-Garfias,Divya Mirchandani,Dionna Scharton,John P Bilello,Zhiqiang Ku,Zhiqiang An,Birte Kalveram,Alexander N. Freiberg,Vineet D. Menachery,Xuping Xie,Kenneth S. Plante,Scott C. Weaver,Pei Yong Shi +21 more
TL;DR: The D614G mutation significantly enhances SARS-CoV-2 replication on human lung epithelial cells and primary human airway tissues, through an improved infectivity of virions with the spike receptor-binding domain in an “up” conformation for binding to ACE2 receptor.
Journal ArticleDOI
Elevated ACE-2 expression in the olfactory neuroepithelium: implications for anosmia and upper respiratory SARS-CoV-2 entry and replication.
Mengfei Chen,Wenjuan Shen,Nicholas R. Rowan,Heather Kulaga,Alexander T. Hillel,Murugappan Ramanathan,Andrew P. Lane +6 more
TL;DR: Analysis of multiple single cell RNA-seq datasets reveal overall low ACE-2 RNA transcription in nasal airway epithelium, which provides evidence that the upper, rather than the lower, airway is the initial site of SARS-CoV-2 infection.
Posted ContentDOI
Pathophysiology of SARS-CoV-2: targeting of endothelial cells renders a complex disease with thrombotic microangiopathy and aberrant immune response. The Mount Sinai COVID-19 autopsy experience
Clare Bryce,Zachary Grimes,Elisabet Pujadas,Sadhna Ahuja,Mary Beth Beasley,Randy A. Albrecht,Hernandez T,Aryeh Stock,Zhen Zhao,Al Rasheed M,Jia Chen,Li Li,Wang D,Corben A,Haines K,William H. Westra,Melissa Umphlett,Ronald E. Gordon,Jason Reidy,Bruce Petersen,Fadi Salem,Maria Isabel Fiel,El Jamal Sm,Nadejda M. Tsankova,Jane Houldsworth,Zarmeen Mussa,Liu W,Veremis B,Emilia Mia Sordillo,Melissa R. Gitman,Michael D. Nowak,Rachel Brody,Noam Harpaz,Miriam Merad,Sacha Gnjatic,Ryan Donnelly,Seigler P,Keys C,Cameron J,Moultrie I,Washington K,Treatman J,Robert Sebra,Jeffrey S. Jhang,Adolfo Firpo,John A. Lednicky,Alberto Paniz-Mondolfi,Carlos Cordon-Cardo,Mary Fowkes +48 more
TL;DR: Novel findings reported here include an endothelial phenotype of ACE2 in selected organs, which correlates with clotting abnormalities and thrombotic microangiopathy, addressing the prominent coagulopathy and neuropsychiatric symptoms.
Journal ArticleDOI
Furin Inhibitors Block SARS-CoV-2 Spike Protein Cleavage to Suppress Virus Production and Cytopathic Effects
Ya-Wen Cheng,Tai Ling Chao,Chiao Ling Li,Mu Fan Chiu,Han Chieh Kao,Sheng-Han Wang,Yu Hao Pang,Chih Hui Lin,Ya Min Tsai,Wen Hau Lee,Mi-Hua Tao,Tung Ching Ho,Ping-Yi Wu,Li Ting Jang,Pei-Jer Chen,Sui-Yuan Chang,Shiou-Hwei Yeh +16 more
TL;DR: Host proteases that proteolytically activate the SARS-CoV-2 spike protein, critical for its fusion after binding to angiotensin-converting enzyme 2 (ACE2), as antiviral targets are focused on.
Journal ArticleDOI
Coronavirus disease-19 and fertility: viral host entry protein expression in male and female reproductive tissues.
TL;DR: It is suggested that SARS-CoV-2 infection is unlikely to have long-term effects on male and female reproductive function and therefore procedures in which oocytes are collected and fertilized in vitro are associated with very little risk of viral transmission may be susceptible to exposure.
References
More filters
Journal ArticleDOI
Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China
Chaolin Huang,Yeming Wang,Xingwang Li,Lili Ren,Jianping Zhao,Yi Hu,Li Zhang,Guohui Fan,Jiuyang Xu,Xiaoying Gu,Zhenshun Cheng,Ting Yu,Jia'an Xia,Yuan Wei,Wenjuan Wu,Xuelei Xie,Wen Yin,Li Hui,Min Liu,Yan Xiao,Hong Gao,Li Guo,Jungang Xie,Guang-Fa Wang,Rongmeng Jiang,Zhancheng Gao,Qi Jin,Jianwei Wang,Bin Cao +28 more
TL;DR: The epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of patients with laboratory-confirmed 2019-nCoV infection in Wuhan, China, were reported.
Journal ArticleDOI
MEGA X: Molecular Evolutionary Genetics Analysis across Computing Platforms.
TL;DR: The Molecular Evolutionary Genetics Analysis (Mega) software implements many analytical methods and tools for phylogenomics and phylomedicine and has additionally been upgraded to use multiple computing cores for many molecular evolutionary analyses.
Journal ArticleDOI
A Novel Coronavirus from Patients with Pneumonia in China, 2019.
Na Zhu,Dingyu Zhang,Wenling Wang,Xingwang Li,Bo Yang,Jingdong Song,Xiang Zhao,Baoying Huang,Weifeng Shi,Roujian Lu,Peihua Niu,Faxian Zhan,Xuejun Ma,Dayan Wang,Wenbo Xu,Wenbo Xu,Guizhen Wu,George F. Gao,Wenjie Tan +18 more
TL;DR: Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily, which is the seventh member of the family of coronaviruses that infect humans.
Journal ArticleDOI
A pneumonia outbreak associated with a new coronavirus of probable bat origin
Peng Zhou,Xing-Lou Yang,Xian Guang Wang,Ben Hu,Lei Zhang,Wei Zhang,Hao Rui Si,Yan Zhu,Bei Li,Chao Lin Huang,Hui-Dong Chen,Jing Chen,Yun Luo,Hua Guo,Ren Di Jiang,Meiqin Liu,Ying Chen,Xu Rui Shen,Xi Wang,Xiao Shuang Zheng,Kai Zhao,Quanjiao Chen,Fei Deng,Lin Lin Liu,Bing Yan,Fa Xian Zhan,Yan-Yi Wang,Gengfu Xiao,Zhengli Shi +28 more
TL;DR: Identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China, and it is shown that this virus belongs to the species of SARSr-CoV, indicates that the virus is related to a bat coronav virus.
Journal ArticleDOI
A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster.
Jasper Fuk-Woo Chan,Shuofeng Yuan,Kin-Hang Kok,Kelvin K. W. To,Kelvin K. W. To,Hin Chu,Jin Yang,Fanfan Xing,Jieling Liu,Cyril C. Y. Yip,Rosana W.S. Poon,Hoi Wah Tsoi,Simon Kam Fai Lo,Kwok-Hung Chan,Vincent Kwok-Man Poon,Wan Mui Chan,Jonathan Daniel Ip,Jian Piao Cai,Vincent C.C. Cheng,Honglin Chen,Honglin Chen,Christopher K.M. Hui,Kwok-Yung Yuen +22 more
TL;DR: The findings are consistent with person-to-person transmission of this novel coronavirus in hospital and family settings, and the reports of infected travellers in other geographical regions.
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