Phosphatidylserine Receptors Enhance SARS-CoV-2 Infection: AXL as a Therapeutic Target for COVID-19

Bohan, Dana; Ert, Hanora Van; Ruggio, Natalie; Rogers, Kai J.; Badreddine, Mohammad; Briseno, J. A. Aguilar; Chávez, Roberth Anthony Rojas; Gao, Boning; Stokowy, Tomasz; Christakou, Eleni; Micklem, David; Gausdal, Gro; Haim, Hillel; Minna, John D.; Lorens, James B.; Maury, Wendy

doi:10.1101/2021.06.15.448419

Cited by 12 publications

(23 citation statements)

References 59 publications

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“…These data are in contrast to the conclusions of another report, which points out that AXL does not interact with SARS-CoV-2 spike proteins, and neither does it mediate SARS-CoV-2 entry unilaterally, however, it is a host factor promoting SARS-CoV-2 entry (39). Under synergistic effects of low-level ACE2, AXL interacted with viral particle-related phosphatidylserine (PS) to enhance SARS-CoV-2 infection, while the effects of AXL were no longer observed at high ACE2 levels (39). Since expression levels of ACE2 in the lungs are low, AXL may be highly correlated with SARS-CoV-2 infections.…”

Section: Receptor: Axlcontrasting

confidence: 99%

COVID-19 and Diabetes: A Comprehensive Review of Angiotensin Converting Enzyme 2, Mutual Effects and Pharmacotherapy

et al. 2021

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The potential relationship between diabetes and COVID-19 has been evaluated. However, new knowledge is rapidly emerging. In this study, we systematically reviewed the relationship between viral cell surface receptors (ACE2, AXL, CD147, DC-SIGN, L-SIGN and DPP4) and SARS-CoV-2 infection risk, and emphasized the implications of ACE2 on SARS-CoV-2 infection and COVID-19 pathogenesis. Besides, we updated on the two-way interactions between diabetes and COVID-19, as well as the treatment options for COVID-19 comorbid patients from the perspective of ACE2. The efficacies of various clinical chemotherapeutic options, including anti-diabetic drugs, renin-angiotensin-aldosterone system inhibitors, lipid-lowering drugs, anticoagulants, and glucocorticoids for COVID-19 positive diabetic patients were discussed. Moreover, we reviewed the significance of two different forms of ACE2 (mACE2 and sACE2) and gender on COVID-19 susceptibility and severity. This review summarizes COVID-19 pathophysiology and the best strategies for clinical management of diabetes patients with COVID-19.

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Section: Receptor: Axlcontrasting

confidence: 99%

COVID-19 and Diabetes: A Comprehensive Review of Angiotensin Converting Enzyme 2, Mutual Effects and Pharmacotherapy

et al. 2021

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“…Research showed that the binding affinity of SARS-CoV-2 to ACE2 was similar to or even higher than the binding affinity of SARS-CoV to ACE2, consistent with the high structural similarity between SARS-CoV-2 and SARS-CoV [83][84][85][86]. Additionally, neuropilin-1 (NRP-1) and the tyrosine-protein kinase receptor UFO (AXL) were identified as receptors to facilitate SARS-CoV-2 infection of the human respiratory system [87][88][89][90]. The overall structural homology and high affinity to the same receptor of these two viruses may explain the high transmission rates of SARS and COVID-19 from human to human [84,85].…”

Section: The Structure and Pathogenesis Of Sars-cov-2mentioning

confidence: 73%

COVID-19: The Disease, the Immunological Challenges, the Treatment with Pharmaceuticals and Low-Dose Ionizing Radiation

Azzam

Jadhav

et al. 2021

Cells

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The year 2020 will be carved in the history books—with the proliferation of COVID-19 over the globe and with frontline health workers and basic scientists worldwide diligently fighting to alleviate life-threatening symptoms and curb the spread of the disease. Behind the shocking prevalence of death are countless families who lost loved ones. To these families and to humanity as a whole, the tallies are not irrelevant digits, but a motivation to develop effective strategies to save lives. However, at the onset of the pandemic, not many therapeutic choices were available besides supportive oxygen, anti-inflammatory dexamethasone, and antiviral remdesivir. Low-dose radiation (LDR), at a much lower dosage than applied in cancer treatment, re-emerged after a 75-year silence in its use in unresolved pneumonia, as a scientific interest with surprising effects in soothing the cytokine storm and other symptoms in severe COVID-19 patients. Here, we review the epidemiology, symptoms, immunological alterations, mutations, pharmaceuticals, and vaccine development of COVID-19, summarizing the history of X-ray irradiation in non-COVID diseases (especially pneumonia) and the currently registered clinical trials that apply LDR in treating COVID-19 patients. We discuss concerns, advantages, and disadvantages of LDR treatment and potential avenues that may provide empirical evidence supporting its potential use in defending against the pandemic.

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“…Phosphatidylserine (PS) is expressed in the outer leaflet of the viral envelope, with a symmetrical location rather than the asymmetrical phospholipid distribution observed in the normal plasma membrane [5]. As with all enveloped viruses, this facilitates cell entry of SARS-CoV-2 using the apoptotic mimicry pathway [6]. PS receptors (PSRs), Axl in particular, was shown to potentiate the binding and uptake of SARS-CoV-2 [6].…”

Section: Sars-cov-2 Infection and Efferocytosismentioning

confidence: 99%

“…As with all enveloped viruses, this facilitates cell entry of SARS-CoV-2 using the apoptotic mimicry pathway [6]. PS receptors (PSRs), Axl in particular, was shown to potentiate the binding and uptake of SARS-CoV-2 [6].…”

Section: Sars-cov-2 Infection and Efferocytosismentioning

confidence: 99%

“…A large number of different PSRs that recognize PS directly and indirectly in phagocytic cells facilitate the functioning of the efferocytosis process [5,6,14]. While TIM receptors (T cell immunoglobulin and mucin domain-containing molecule) provide direct binding, TAM (Tyro3, Axl, and MerTK) receptors indirectly bind to apoptotic cells via mediator molecules such as Gas6 and protein S (ProS) [5,18].…”

Section: Sars-cov-2 Infection and Efferocytosismentioning

confidence: 99%

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Defective efferocytosis as a predictor of COVID-19 mortality

Erol¹

2021

Preprint

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COVID-19 is a generally benign coronavirus disease that can spread rapidly, except for those with a group of risk factors. Since the pathogenesis responsible for the severity of the disease has not been clearly revealed, effective treatment alternatives has not been developed. The hallmark of the SARS-CoV-2-infected cells is apoptosis. Apoptotic cells are cleared through a sterile process defined as efferocytosis by professional and nonprofessional phagocytic cells. The disease would be rapidly brought under control in the organism that can achieve effective efferocytosis, which is also a kind of innate immune response. In the risk group, the efferocytic process is defective. By the addition of the apoptotic cell load associated with SARS-COV-2 infection, failure to achieve efferocytosis of dying cells can initiate secondary necrosis that is a highly destructive process. Uncontrolled inflammation and coagulation abnormalities caused by secondary necrosis reason in various organ failures, lung in particular, which are responsible for the poor prognosis. Following the short and simplified information, this opinion paper aims to present possible treatment options that can control the severity of COVID-19 by detailing the mechanisms that can cause defective efferocytosis.

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Phosphatidylserine Receptors Enhance SARS-CoV-2 Infection: AXL as a Therapeutic Target for COVID-19

Cited by 12 publications

References 59 publications

COVID-19 and Diabetes: A Comprehensive Review of Angiotensin Converting Enzyme 2, Mutual Effects and Pharmacotherapy

COVID-19 and Diabetes: A Comprehensive Review of Angiotensin Converting Enzyme 2, Mutual Effects and Pharmacotherapy

COVID-19: The Disease, the Immunological Challenges, the Treatment with Pharmaceuticals and Low-Dose Ionizing Radiation

Defective efferocytosis as a predictor of COVID-19 mortality

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