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Patient-Derived Mutations Impact Pathogenicity of SARS-CoV-2

57 Pages Posted: 30 Apr 2020 Sneak Peek Status: Review Complete

See all articles by Hang-Ping Yao

Hang-Ping Yao

Zhejiang University - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases

Xiangyun Lu

Zhejiang University - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases

Qiong Chen

Zhejiang University - Institute of Life Sciences

Kaijin Xu

Zhejiang University - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases

Yu Chen

Zhejiang University - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases

Linfang Cheng

Zhejiang University - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases

Fumin Liu

Zhejiang University - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases

Zhigang Wu

Zhejiang University - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases

Haibo Wu

Zhejiang University - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases

Changzhong Jin

Zhejiang University - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases

Min Zheng

Zhejiang University - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases

Nanping Wu

Zhejiang University - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases

Chao Jiang

Zhejiang University - Institute of Life Sciences

Lanjuan Li

Zhejiang University - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases

More...

Abstract

The sudden outbreak of the severe acute respiratory syndrome–coronavirus (SARS-CoV-2) has spread globally with more than 1,300,000 patients diagnosed and a death toll of 70,000. Current genomic survey data suggest that single nucleotide variants (SNVs) are abundant. However, no mutation has been directly linked with functional changes in viral pathogenicity. We report functional characterizations of 11 patient-derived viral isolates. We observed diverse mutations in these viral isolates, including 6 different mutations in the spike glycoprotein (S protein), and 2 of which are different SNVs that led to the same missense mutation. Importantly, these viral isolates show significant variation in cytopathic effects and viral load, up to 270-fold differences, when infecting Vero-E6 cells. Therefore, we provide direct evidence that the SARS-CoV-2 has acquired mutations capable of substantially changing its pathogenicity.

Funding: This work was supported by funds from Major Project of Zhejiang Provincial Science and Technology Department #2020C03123, National Science and Technology Major Project for the Control and Prevention of Major Infectious Diseases in China (2018ZX10711001, 2018ZX10102001, 2018ZX10302206), and start-606 up funds from Life Sciences Institute at Zhejiang University.

Conflict of Interest: None.

Ethical Approval: The study was approved by the Clinical Research Ethics Committee of The First Affiliated Hospital, School of Medicine, Zhejiang University (Approval notice 2020-29) for emerging infectious diseases.

Keywords: SARS-CoV-2, COVID-19, Mutational impact on viral pathogenicity, Evolution, Infectious diseases

Suggested Citation

Yao, Hang-Ping and Lu, Xiangyun and Chen, Qiong and Xu, Kaijin and Chen, Yu and Cheng, Linfang and Liu, Fumin and Wu, Zhigang and Wu, Haibo and Jin, Changzhong and Zheng, Min and Wu, Nanping and Jiang, Chao and Li, Lanjuan, Patient-Derived Mutations Impact Pathogenicity of SARS-CoV-2. Available at SSRN: https://ssrn.com/abstract=3578153 or http://dx.doi.org/10.2139/ssrn.3578153
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Hang-Ping Yao

Zhejiang University - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases ( email )

38 Zheda Road
Hangzhou, Zhejiang 310058
China

Xiangyun Lu

Zhejiang University - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases

China

Qiong Chen

Zhejiang University - Institute of Life Sciences

China

Kaijin Xu

Zhejiang University - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases

38 Zheda Road
Hangzhou, Zhejiang 310058
China

Yu Chen

Zhejiang University - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases ( email )

38 Zheda Road
Hangzhou, Zhejiang 310058
China

Linfang Cheng

Zhejiang University - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases ( email )

China

Fumin Liu

Zhejiang University - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases ( email )

China

Zhigang Wu

Zhejiang University - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases

China

Haibo Wu

Zhejiang University - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases

China

Changzhong Jin

Zhejiang University - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases ( email )

China

Min Zheng

Zhejiang University - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases ( email )

China

Nanping Wu

Zhejiang University - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases ( email )

China

Chao Jiang

Zhejiang University - Institute of Life Sciences ( email )

China

Lanjuan Li (Contact Author)

Zhejiang University - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases ( email )

38 Zheda Road
Hangzhou, Zhejiang 310058
China

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