Characterization of spike glycoprotein of 2019-nCoV on virus entry and its immune cross-reactivity with spike glycoprotein of SARS-CoV
Abstract Since beginning of this century, there have already been three zoonotic outbreaks caused by beta coronaviruses (CoV), SARS-CoV in 2002-2003, MERS-CoV in 2012, and the newly identified 2019-nCoV in late 2019, Wuhan, China. As to Feb 10th, 2020, there are over 40,000 confirmed cases and over 900 deaths. However, little is known about the biology of this newly emerged virus. Here we developed a lentiviral based pseudovirus system for S protein of 2019-nCoV to study virus entry in BSL2 settings. First, we confirmed that human angiotensin converting enzyme 2 (hACE2) is the main entry receptor for 2019-nCoV. Second, we found that 2019-nCoV S protein mediated entry on 293/hACE2 cells was mainly through endocytosis, and PIKfyve, TPC2, and cathepsin L are critical for virus entry. Third, 2019-nCoV S protein is less stable than SARS-CoV, and it could trigger protease-independent and receptor dependent cell-cell fusion, which might help virus rapidly spread from cell to cell. Finally and more importantly, polyclonal anti-SARS S1 antibodies T62 effectively inhibited entry of SARS-CoV S pseudovirions, but almost had no effect on entry of 2019-nCoV S pseudovirions. Further studies using sera from one recovered SARS-CoV patient and five 2019-nCoV patients showed that there was only limited cross-neutralization activities between SARS-CoV and 2019-nCoV sera, suggesting that recovery from one infection might not protect against the other. Our results present potential targets for development of drugs and vaccines for 2019-nCoV..
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Preprint| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
ResearchSquare.com - (2022) vom: 28. Juli Zur Gesamtaufnahme - year:2022 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ou, Xiuyuan [VerfasserIn] |
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| doi: |
10.21203/rs.2.24016/v1 |
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| PPN (Katalog-ID): |
XRA034523499 |
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| 520 | |a Abstract Since beginning of this century, there have already been three zoonotic outbreaks caused by beta coronaviruses (CoV), SARS-CoV in 2002-2003, MERS-CoV in 2012, and the newly identified 2019-nCoV in late 2019, Wuhan, China. As to Feb 10th, 2020, there are over 40,000 confirmed cases and over 900 deaths. However, little is known about the biology of this newly emerged virus. Here we developed a lentiviral based pseudovirus system for S protein of 2019-nCoV to study virus entry in BSL2 settings. First, we confirmed that human angiotensin converting enzyme 2 (hACE2) is the main entry receptor for 2019-nCoV. Second, we found that 2019-nCoV S protein mediated entry on 293/hACE2 cells was mainly through endocytosis, and PIKfyve, TPC2, and cathepsin L are critical for virus entry. Third, 2019-nCoV S protein is less stable than SARS-CoV, and it could trigger protease-independent and receptor dependent cell-cell fusion, which might help virus rapidly spread from cell to cell. Finally and more importantly, polyclonal anti-SARS S1 antibodies T62 effectively inhibited entry of SARS-CoV S pseudovirions, but almost had no effect on entry of 2019-nCoV S pseudovirions. Further studies using sera from one recovered SARS-CoV patient and five 2019-nCoV patients showed that there was only limited cross-neutralization activities between SARS-CoV and 2019-nCoV sera, suggesting that recovery from one infection might not protect against the other. Our results present potential targets for development of drugs and vaccines for 2019-nCoV. | ||
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| 700 | 1 | |a Liu, Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Lei, Xiaobo |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Pei |e verfasserin |4 aut | |
| 700 | 1 | |a Mi, Dan |e verfasserin |4 aut | |
| 700 | 1 | |a Ren, Lili |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Li |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Ting |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Jiaxing |e verfasserin |4 aut | |
| 700 | 1 | |a Xiang, Zichun |e verfasserin |4 aut | |
| 700 | 1 | |a Mu, Zhixia |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Xing |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Jieyong |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Keping |e verfasserin |4 aut | |
| 700 | 1 | |a Jin, Qi |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Jianwei |e verfasserin |4 aut | |
| 700 | 1 | |a Qian, Zhaohui |e verfasserin |4 aut | |
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