CD147-spike protein interaction in COVID-19: Get the ball rolling with a novel receptor and therapeutic target

Behl, Tapan; Kaur, Ishnoor; Aleya, Lotfi; Sehgal, Aayush; Singh, Sukhbir; Sharma, Neelam; Bhatia, Saurabh; Al‐Harrasi, Ahmed; Bungău, Simona

doi:10.1016/j.scitotenv.2021.152072

Cited by 91 publications

(94 citation statements)

References 157 publications

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“…In addition to the ACE2/TMPRSS2 major entrance sites, alternative pathways of SARS-CoV2 entering cells have also attracted attention of researchers since targeting ACE2/MPRSS2 pathway has not achieved the expected therapeutic effects. The cluster of differentiation 147 (CD147) transmembrane protein may be another entry receptor and mediator of endocytosis-promoted entry of the SARS-CoV-2 [74] , [75] . It has been speculated that melatonin can reduce the increased CD147 activation during a SARS-CoV-2 infection by suppressing HIF-1ɑ expression; the mechanisms for this action have been discussed in an extensive review [76] ( Fig.…”

Section: Melatonin Targets Sars-cov-2: Inhibiting Its Cellular Entran...mentioning

confidence: 99%

“…The crystal structure of SARS-CoV-2 Mpro and PF-07321332 complex shows that the PF-07321332 is located in the catalytic center of Mpro. At this site, the Sγ atom of the C145 forms a 1.8-Å C—S covalent bond with the nitrile carbon of PF-07321332 and H41 binds to PF-07321332 via carbon‑hydrogen bond [74] , [75] . Interestingly, similar to PF-07321332, melatonin also localizes in the catalytic site of Mpro and binds to the catalytic amino acid residues of C145 and H41 with pi‑sulfur/conventional hydrogen bonds and carbon‑hydrogen bonds, respectively [70] .…”

Section: Melatonin Targets Sars-cov-2: Inhibiting Its Cellular Entran...mentioning

confidence: 99%

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Mechanisms and clinical evidence to support melatonin's use in severe COVID-19 patients to lower mortality

Tan

Reíter

2022

Life Sciences

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Section: Melatonin Targets Sars-cov-2: Inhibiting Its Cellular Entran...mentioning

confidence: 99%

Section: Melatonin Targets Sars-cov-2: Inhibiting Its Cellular Entran...mentioning

confidence: 99%

Mechanisms and clinical evidence to support melatonin's use in severe COVID-19 patients to lower mortality

Tan

Reíter

2022

Life Sciences

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“…In addition to ACE2, another significant receptor for SARS-CoV-2 has also been identified—cluster of differentiation 147 (CD147) or basigin or extracellular matrix metalloproteinase inducer. CD147 is a transmembrane protein, that contributes to the development of tumors and bacterial and viral infections [ 48 ]. The study of RNA sequencing of human cells showed that ACE2 was expressed in lung and skin epithelial sites, while CD147 was expressed both in epithelial and immune cells.…”

Section: Ace2 Cd147 and Melatoninmentioning

confidence: 99%

Potential and Possible Therapeutic Effects of Melatonin on SARS-CoV-2 Infection

et al. 2022

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The absence of effective drugs for COVID-19 prevention and treatment requires the search for new candidates among approved medicines. Fundamental studies and clinical observations allow us to approach an understanding of the mechanisms of damage and protection from exposure to SARS-CoV-2, to identify possible points of application for pharmacological interventions. In this review we presented studies on the anti-inflammatory, antioxidant, and immunotropic properties of melatonin. We have attempted to present scientifically proven mechanisms of action for the potential therapeutic use of melatonin during SARS-CoV-2 infection. A wide range of pharmacological properties allows its inclusion as an effective addition to the methods of prevention and treatment of COVID-19.

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“…61 A few publications focused on CD147 in COVID-19; in fact, this diffusely distributed cell membrane receptor is a wellknown mediator in several diseases, where it exhibits a pleiotropic function. [62][63][64] Cluster of Differentiation 147, or CD147, is a highly glycosylated transmembrane glycoprotein belonging to the immunoglobulin superfamily, compelling for the Ok blood group system. The immunoglobulin superfamily comprehends proteins with at least one Ig domain and is of fundamental importance in intercellular communication.…”

Section: Introductionmentioning

confidence: 99%

COVID-19, Cation Dysmetabolism, Sialic Acid, CD147, ACE2, Viroporins, Hepcidin and Ferroptosis: A Possible Unifying Hypothesis

et al. 2022

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Background: iron and calcium dysmetabolism, with hyperferritinemia, hypoferremia, hypocalcemia and anemia have been documented in the majority of COVID-19 patients at later/worse stages. Furthermore, complementary to ACE2, both sialic acid (SA) molecules and CD147 proved relevant host receptors for SARS-CoV-2 entry, which explains the viral attack to multiple types of cells, including erythrocytes, endothelium and neural tissue. Several authors advocated that cell ferroptosis may be the core and final cell degenerative mechanism. Methods: a literature research was performed in several scientific search engines, such as PubMed Central, Cochrane Library, Chemical Abstract Service. More than 500 articles were retrieved until mid-December 2021, to highlight the available evidence about the investigated issues. Results: based on COVID-19 literature data, we have highlighted a few pathophysiological mechanisms, associated with virus-based cation dysmetabolism, multi-organ attack, mitochondria degeneration and ferroptosis. Our suggested elucidated pathological sequence is: a) spike protein subunit S1 docking with sialylated membrane glycoproteins/receptors (ACE2, CD147), and S2 subunit fusion with the lipid layer; b) cell membrane morpho-functional changes due to the consequent electro-chemical variations and viroporin action, which induce an altered ion channel function and intracellular cation accumulation; c) additional intracellular iron concentration due to a deregulated hepcidin-ferroportin axis, with higher hepcidin levels. Viral invasion may also affect erythrocytes/erythroid precursors, endothelial cells and macrophages, through SA and CD147 receptors, with relative hemoglobin and iron/calcium dysmetabolism. AB0 blood group, hemochromatosis, or environmental elements may represent possible factors which affect individual susceptibility to COVID-19. Conclusions: our literature analysis confirms the combined role of SA molecules, ACE2, CD147, viroporins and hepcidin in determining the cation dysmetabolism and final ferroptosis in the cells infected by SARS-CoV-2. The altered ion channels and electrochemical gradients of the cell membrane have a pivotal role in the virus entry and cell dysmetabolism, with subsequent multi-organ immune-inflammatory degeneration and erythrocyte/hemoglobin alterations.

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CD147-spike protein interaction in COVID-19: Get the ball rolling with a novel receptor and therapeutic target

Cited by 91 publications

References 157 publications

Mechanisms and clinical evidence to support melatonin's use in severe COVID-19 patients to lower mortality

Mechanisms and clinical evidence to support melatonin's use in severe COVID-19 patients to lower mortality

Potential and Possible Therapeutic Effects of Melatonin on SARS-CoV-2 Infection

COVID-19, Cation Dysmetabolism, Sialic Acid, CD147, ACE2, Viroporins, Hepcidin and Ferroptosis: A Possible Unifying Hypothesis

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