Đặc trưng của glycoprotein đỉnh của SARS-CoV-2 trong quá trình xâm nhập virus và sự phản ứng miễn dịch chéo của nó với SARS-CoV

Nature Communications - Tập 11 Số 1
Xiuyuan Ou1, Yan Liu1, Xiaobo Lei1, Pei Li1, Dan Mi1, Lili Ren1, Li Guo1, Ruixuan Guo1, Ting Chen1, Jiaxin Hu1, Zichun Xiang1, Zhixia Mu1, Xing Chen2, Jieyong Chen3, Keping Hu2, Qi Jin1, Jianwei Wang1, Zhaohui Qian1
1NHC Key laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, 100176, Beijing, China
2Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical Collage (PUMC), 151 Malianwa Road North, Haidian District, 100193, Beijing, China
3Hengshui Third People's Hospital, Heibei, China

Tóm tắt

Tóm tắt

Kể từ năm 2002, các coronavirus beta (CoV) đã gây ra ba đợt bùng phát zoonotic, SARS-CoV vào năm 2002–2003, MERS-CoV vào năm 2012, và SARS-CoV-2 mới nổi vào cuối năm 2019. Tuy nhiên, hiện tại, kiến thức về sinh học của SARS-CoV-2 còn rất hạn chế. Ở đây, bằng cách sử dụng hệ thống pseudovirus có protein S của SARS-CoV-2, chúng tôi xác nhận rằng enzyme chuyển đổi angiotensin 2 ở người (hACE2) là thụ thể cho SARS-CoV-2, phát hiện rằng SARS-CoV-2 xâm nhập vào các tế bào 293/hACE2 chủ yếu thông qua quá trình nội bào, rằng PIKfyve, TPC2 và cathepsin L là những yếu tố quan trọng cho quá trình xâm nhập, và rằng protein S của SARS-CoV-2 kém ổn định hơn so với protein S của SARS-CoV. Kháng thể đa dòng chống lại SARS S1 T62 ức chế sự xâm nhập của SARS-CoV S nhưng không phải của các pseudovirion SARS-CoV-2 S. Các nghiên cứu tiếp theo sử dụng huyết thanh của bệnh nhân hồi phục từ SARS và COVID-19 cho thấy sự trung hòa chéo hạn chế, gợi ý rằng việc hồi phục từ một loại nhiễm trùng có thể không bảo vệ chống lại loại còn lại. Kết quả của chúng tôi trình bày những mục tiêu tiềm năng cho việc phát triển thuốc và vắc-xin dành cho SARS-CoV-2.

Từ khóa


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