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Nonmuscle myosin heavy chain IIA facilitates SARS-CoV-2 infection in human pulmonary cells.
Chen, Jian; Fan, Jun; Chen, Zhilu; Zhang, Miaomiao; Peng, Haoran; Liu, Jian; Ding, Longfei; Liu, Mingbin; Zhao, Chen; Zhao, Ping; Zhang, Shuye; Zhang, Xiaoyan; Xu, Jianqing.
  • Chen J; Zhongshan Hospital, Institutes of Biomedical Sciences, Fudan University, Shanghai 201508, China.
  • Fan J; Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China.
  • Chen Z; Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China.
  • Zhang M; Zhongshan Hospital, Institutes of Biomedical Sciences, Fudan University, Shanghai 201508, China.
  • Peng H; Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China.
  • Liu J; Department of Microbiology, Second Military Medical University, Shanghai 200433, China.
  • Ding L; Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China.
  • Liu M; Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China.
  • Zhao C; Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China.
  • Zhao P; Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China.
  • Zhang S; Department of Microbiology, Second Military Medical University, Shanghai 200433, China pnzhao@163.com zhangshuye@shphc.org.cn zhangxiaoyan@shphc.org.cn xujianqing@shphc.org.cn.
  • Zhang X; Zhongshan Hospital, Institutes of Biomedical Sciences, Fudan University, Shanghai 201508, China; pnzhao@163.com zhangshuye@shphc.org.cn zhangxiaoyan@shphc.org.cn xujianqing@shphc.org.cn.
  • Xu J; Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China.
Proc Natl Acad Sci U S A ; 118(50)2021 12 14.
Article in English | MEDLINE | ID: covidwho-1555255
ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), binds to host receptor angiotensin-converting enzyme 2 (ACE2) through its spike (S) glycoprotein, which mediates membrane fusion and viral entry. However, the expression of ACE2 is extremely low in a variety of human tissues, especially in the airways. Thus, other coreceptors and/or cofactors on the surface of host cells may contribute to SARS-CoV-2 infection. Here, we identified nonmuscle myosin heavy chain IIA (MYH9) as an important host factor for SARS-CoV-2 infection of human pulmonary cells by using APEX2 proximity-labeling techniques. Genetic ablation of MYH9 significantly reduced SARS-CoV-2 pseudovirus infection in wild type (WT) A549 and Calu-3 cells, and overexpression of MYH9 enhanced the pseudovirus infection in WT A549 and H1299 cells. MYH9 was colocalized with the SARS-CoV-2 S and directly interacted with SARS-CoV-2 S through the S2 subunit and S1-NTD (N-terminal domain) by its C-terminal domain (designated as PRA). Further experiments suggested that endosomal or myosin inhibitors effectively block the viral entry of SARS-CoV-2 into PRA-A549 cells, while transmembrane protease serine 2 (TMPRSS2) and cathepsin B and L (CatB/L) inhibitors do not, indicating that MYH9 promotes SARS-CoV-2 endocytosis and bypasses TMPRSS2 and CatB/L pathway. Finally, we demonstrated that loss of MYH9 reduces authentic SARS-CoV-2 infection in Calu-3, ACE2-A549, and ACE2-H1299 cells. Together, our results suggest that MYH9 is a candidate host factor for SARS-CoV-2, which mediates the virus entering host cells by endocytosis in an ACE2-dependent manner, and may serve as a potential target for future clinical intervention strategies.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Myosin Heavy Chains / SARS-CoV-2 / COVID-19 Type of study: Prognostic study Limits: Humans Language: English Year: 2021 Document Type: Article Affiliation country: Pnas.2111011118

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Myosin Heavy Chains / SARS-CoV-2 / COVID-19 Type of study: Prognostic study Limits: Humans Language: English Year: 2021 Document Type: Article Affiliation country: Pnas.2111011118