AXL Promotes SARS-CoV-2 Infection of Pulmonary and Bronchial Epithelial Cells

Wang, Shuai; Qiu, Zongyang; Hou, Yingnan; Deng, Xiya; Zheng, Tianhang; Yan, Renhong; Wu, Peihan; Xie, Shengling; Zhou, Quan; Huang, Jing; Xu, Le

doi:10.21203/rs.3.rs-35387/v1

Cited by 29 publications

(33 citation statements)

References 25 publications

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“…Most of the CoVs enter cells by interacting with the RBD domain from S protein with the ACE2 receptor [ 199 ]. The ACE2 receptor is a widely expressed protein in the cell membrane of many tissues such as lungs, heart, kidney, renal, cardiovascular, and intestine [ 200 ]. Discovered in 2000, ACE2 holds 61% of similarity with ACE.…”

Section: Biological Roles Of the S Proteinmentioning

confidence: 99%

The human pandemic coronaviruses on the show: The spike glycoprotein as the main actor in the coronaviruses play

Souza

Mesquita

Amaral

et al. 2021

International Journal of Biological Macromolecules

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Three coronaviruses (CoVs) have threatened the world population by causing outbreaks in the last two decades. In late 2019, the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged and caused the coronaviruses to disease 2019 (COVID-19), leading to the ongoing global outbreak. The other pandemic coronaviruses, SARS-CoV and Middle East respiratory syndrome CoV (MERS-CoV), share a considerable level of similarities at genomic and protein levels. However, the differences between them lead to distinct behaviors. These differences result from the accumulation of mutations in the sequence and structure of spike (S) glycoprotein, which plays an essential role in coronavirus infection, pathogenicity, transmission, and evolution. In this review, we brought together many studies narrating a sequence of events and highlighting the differences among S proteins from SARS-CoV, MERS-CoV, and SARS-CoV-2. It was performed here, analysis of S protein sequences and structures from the three pandemic coronaviruses pointing out the mutations among them and what they come through. Additionally, we investigated the receptor-binding domain (RBD) from all S proteins explaining the mutation and biological importance of all of them. Finally, we discuss the mutation in the S protein from several new isolates of SARS-CoV-2, reporting their difference and importance. This review brings into detail how the variations in S protein that make SARS-CoV-2 more aggressive than its relatives coronaviruses and other differences between coronaviruses.

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Section: Biological Roles Of the S Proteinmentioning

confidence: 99%

The human pandemic coronaviruses on the show: The spike glycoprotein as the main actor in the coronaviruses play

Souza

Mesquita

Amaral

et al. 2021

International Journal of Biological Macromolecules

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“…According to this view, GAS6 and TAMs would be expected to participate in COVID-19 viral entry ( Figure 3 ). Actually, a preprint publication suggests an interaction of AXL with SARS-CoV2 promoting infection in epithelial cells [ 105 ]. In line with it, the AXL inhibitor gilteritinib, which is an FDA-approved drug for the treatment of acute myeloid leukemia, was recently demonstrated to possess antiviral efficacy against SARS-CoV-2 infection in Vero E6 cells, providing additional grounds for GAS6/AXL targeting as a promising anti-COVID-19 treatment [ 106 ].…”

Section: Viral Infectionmentioning

confidence: 99%

Role of Vitamin K-Dependent Factors Protein S and GAS6 and TAM Receptors in SARS-CoV-2 Infection and COVID-19-Associated Immunothrombosis

Tutusaus

Marı́

Ortiz-Pérez

et al. 2020

Cells

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The vitamin K-dependent factors protein S (PROS1) and growth-arrest-specific gene 6 (GAS6) and their tyrosine kinase receptors TYRO3, AXL, and MERTK, the TAM subfamily of receptor tyrosine kinases (RTK), are key regulators of inflammation and vascular response to damage. TAM signaling, which has largely studied in the immune system and in cancer, has been involved in coagulation-related pathologies. Because of these established biological functions, the GAS6-PROS1/TAM system is postulated to play an important role in SARS-CoV-2 infection and progression complications. The participation of the TAM system in vascular function and pathology has been previously reported. However, in the context of COVID-19, the role of TAMs could provide new clues in virus-host interplay with important consequences in the way that we understand this pathology. From the viral mimicry used by SARS-CoV-2 to infect cells, to the immunothrombosis that is associated with respiratory failure in COVID-19 patients, TAM signaling seems to be involved at different stages of the disease. TAM targeting is becoming an interesting biomedical strategy, which is useful for COVID-19 treatment now, but also for other viral and inflammatory diseases in the future.

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“…Functional S1 can bind the ACE2 receptor through its receptor biding domain (RBD), while S2 mediates viral fusion with the host cell membrane and release into the cytoplasm [ 35 ]. Besides ACE2, cellular glycans, integrins, neuropilin 1, and AXL have been involved as entry co-factors [ 36 , 37 , 38 ]. After cell entry, the viral genome is released into the cytoplasm, where it is directly translated by ribosomes into two large polyproteins, polyprotein (pp) 1a and pp1ab, which are cleaved by host and viral proteases to release nonstructural viral proteins, including viral RNA-dependent RNA polymerase, two viral proteases and other components of the viral replication, and transcription complex.…”

Section: Genetic and Biological Features Of Sars-cov-2mentioning

confidence: 99%

SARS-CoV-2 Infection and Disease Modelling Using Stem Cell Technology and Organoids

Trevisan

Riccetti

Sinigaglia

et al. 2021

IJMS

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In this Review, we briefly describe the basic virology and pathogenesis of SARS-CoV-2, highlighting how stem cell technology and organoids can contribute to the understanding of SARS-CoV-2 cell tropisms and the mechanism of disease in the human host, supporting and clarifying findings from clinical studies in infected individuals. We summarize here the results of studies, which used these technologies to investigate SARS-CoV-2 pathogenesis in different organs. Studies with in vitro models of lung epithelia showed that alveolar epithelial type II cells, but not differentiated lung alveolar epithelial type I cells, are key targets of SARS-CoV-2, which triggers cell apoptosis and inflammation, while impairing surfactant production. Experiments with human small intestinal organoids and colonic organoids showed that the gastrointestinal tract is another relevant target for SARS-CoV-2. The virus can infect and replicate in enterocytes and cholangiocytes, inducing cell damage and inflammation. Direct viral damage was also demonstrated in in vitro models of human cardiomyocytes and choroid plexus epithelial cells. At variance, endothelial cells and neurons are poorly susceptible to viral infection, thus supporting the hypothesis that neurological symptoms and vascular damage result from the indirect effects of systemic inflammatory and immunological hyper-responses to SARS-CoV-2 infection.

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AXL Promotes SARS-CoV-2 Infection of Pulmonary and Bronchial Epithelial Cells

Cited by 29 publications

References 25 publications

The human pandemic coronaviruses on the show: The spike glycoprotein as the main actor in the coronaviruses play

The human pandemic coronaviruses on the show: The spike glycoprotein as the main actor in the coronaviruses play

Role of Vitamin K-Dependent Factors Protein S and GAS6 and TAM Receptors in SARS-CoV-2 Infection and COVID-19-Associated Immunothrombosis

SARS-CoV-2 Infection and Disease Modelling Using Stem Cell Technology and Organoids

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