SARS-CoV-2 hijacks macropinocytosis to facilitate its entry and promote viral spike–mediated cell-to-cell fusion

Zhang, Yuyuan; Liang, Ronghui; Wang, Shujie; Ye, Zi‐Wei; Wang, Tong-Yun; Chen, Meng; Li, Jianbo; Lei, Na; Yang, Yue-Lin; Yang, Yong; Yuan, Shuofeng; Yin, Xin; Cai, Xuehui; Tang, Yan-Dong

doi:10.1016/j.jbc.2022.102511

Cited by 22 publications

(15 citation statements)

References 44 publications

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“…Our subsequent experiments revealed that the compound specifically limited SARS-CoV-2 entry by macropinocytosis. Of note, published studies had reported conflicting views about SARS-CoV-2 mode of entry, with some reporting clathrin-dependent endocytosis as the preferred route 25 while others implicating macropinocytosis 26 . Our TEM analysis was clarifying in this regard, illustrating how SARS-CoV-2 can simultaneously use both entry pathways, yet only macropinocytosis is inhibited by virapinib.…”

Section: Discussionmentioning

confidence: 99%

Discovery of a novel inhibitor of macropinocytosis with antiviral activity

Porebski,

Christ,

Corman

et al. 2023

Preprint

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Several viruses hijack various forms of endocytosis in order to infect host cells. Here, we report the discovery of a new molecule with antiviral properties that we named virapinib, which limits viral entry by macropinocytosis. The identification of virapinib derives from a chemical screen using High-Throughput Microscopy, where we identified new chemical entities capable of preventing infection with a pseudotype virus expressing the spike (S) protein from SARS-CoV-2. Subsequent experiments confirmed the capacity of virapinib to inhibit infection by SARS-CoV-2, as well as by additional viruses, such as Monkeypox virus and TBEV. Mechanistic analyses revealed that the compound inhibited macropinocytosis, limiting this entry route for the viruses. Importantly, virapinib has no significant toxicity to host cells. In summary, we present a new molecule that inhibits viral entry via the endocytic route, offering a new alternative to prevent viral infection.

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Section: Discussionmentioning

confidence: 99%

Discovery of a novel inhibitor of macropinocytosis with antiviral activity

Porebski,

Christ,

Corman

et al. 2023

Preprint

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“…The IFA was performed as described in our previous reports ( Zhang et al., 2021 ; Chen et al., 2022 ; Zhang et al., 2022 ). Briefly, MARC-145 cells were infected with the indicated viruses and then fixed with 4% paraformaldehyde (PFA).…”

Section: Methodsmentioning

confidence: 99%

Minor envelope proteins from GP2a to GP4 contribute to the spread pattern and yield of type 2 PRRSV in MARC-145 cells

Bai,

Sun,

Liu

et al. 2024

Front. Cell. Infect. Microbiol.

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In China, porcine reproductive and respiratory syndrome virus (PRRSV) vaccines are widely used. These vaccines, which contain inactivated and live attenuated vaccines (LAVs), are produced by MARC-145 cells derived from the monkey kidney cell line. However, some PRRSV strains in MARC-145 cells have a low yield. Here, we used two type 2 PRRSV strains (CH-1R and HuN4) to identify the genes responsible for virus yield in MARC-145 cells. Our findings indicate that the two viruses have different spread patterns, which ultimately determine their yield. By replacing the viral envelope genes with a reverse genetics system, we discovered that the minor envelope proteins, from GP2a to GP4, play a crucial role in determining the spread pattern and yield of type 2 PRRSV in MARC-145 cells. The cell-free transmission pattern of type 2 PRRSV appears to be more efficient than the cell-to-cell transmission pattern. Overall, these findings suggest that GP2a to GP4 contributes to the spread pattern and yield of type 2 PRRSV.

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“…Interestingly, low pH causes fragmentation of the influenza virus, enhancing membrane fusion between the viral and endosomal components ( 124 ). In addition, SARS viruses have been found to use macropinocytosis ( 126 , 127 ). Basigin (CD147), one of the extracellular membrane receptors responsible for macropinocytosis of viruses in epithelial and endothelial cells ( 3 , 128 ), has been found to interact with SARS-CoV-2 RBD domain in the human bronchial cell line BEAS-2B.…”

Section: Endocytic Pathways In the Setting Of Ali/ardsmentioning

confidence: 99%

Alveolar-capillary endocytosis and trafficking in acute lung injury and acute respiratory distress syndrome

Kryvenko,

Vadász

2024

Front. Immunol.

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Acute respiratory distress syndrome (ARDS) is associated with high morbidity and mortality but lacks specific therapeutic options. Diverse endocytic processes play a key role in all phases of acute lung injury (ALI), including the initial insult, development of respiratory failure due to alveolar flooding, as a consequence of altered alveolar-capillary barrier function, as well as in the resolution or deleterious remodeling after injury. In particular, clathrin-, caveolae-, endophilin- and glycosylphosphatidyl inositol-anchored protein-mediated endocytosis, as well as, macropinocytosis and phagocytosis have been implicated in the setting of acute lung damage. This manuscript reviews our current understanding of these endocytic pathways and subsequent intracellular trafficking in various phases of ALI, and also aims to identify potential therapeutic targets for patients with ARDS.

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SARS-CoV-2 hijacks macropinocytosis to facilitate its entry and promote viral spike–mediated cell-to-cell fusion

Cited by 22 publications

References 44 publications

Discovery of a novel inhibitor of macropinocytosis with antiviral activity

Discovery of a novel inhibitor of macropinocytosis with antiviral activity

Minor envelope proteins from GP2a to GP4 contribute to the spread pattern and yield of type 2 PRRSV in MARC-145 cells

Alveolar-capillary endocytosis and trafficking in acute lung injury and acute respiratory distress syndrome

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