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1.
Cells ; 10(6)2021 06 08.
Article in English | MEDLINE | ID: covidwho-1264419

ABSTRACT

In late 2019, the betacoronavirus SARS-CoV-2 was identified as the viral agent responsible for the coronavirus disease 2019 (COVID-19) pandemic. Coronaviruses Spike proteins are responsible for their ability to interact with host membrane receptors and different proteins have been identified as SARS-CoV-2 interactors, among which Angiotensin-converting enzyme 2 (ACE2), and Basigin2/EMMPRIN/CD147 (CD147). CD147 plays an important role in human immunodeficiency virus type 1, hepatitis C virus, hepatitis B virus, Kaposi's sarcoma-associated herpesvirus, and severe acute respiratory syndrome coronavirus infections. In particular, SARS-CoV recognizes the CD147 receptor expressed on the surface of host cells by its nucleocapsid protein binding to cyclophilin A (CyPA), a ligand for CD147. However, the involvement of CD147 in SARS-CoV-2 infection is still debated. Interference with both the function (blocking antibody) and the expression (knock down) of CD147 showed that this receptor partakes in SARS-CoV-2 infection and provided additional clues on the underlying mechanism: CD147 binding to CyPA does not play a role; CD147 regulates ACE2 levels and both receptors are affected by virus infection. Altogether, these findings suggest that CD147 is involved in SARS-CoV-2 tropism and represents a possible therapeutic target to challenge COVID-19.


Subject(s)
Angiotensin-Converting Enzyme 2/physiology , Basigin/physiology , SARS-CoV-2/physiology , Virus Internalization , A549 Cells , Angiotensin-Converting Enzyme 2/metabolism , Animals , Basigin/antagonists & inhibitors , Basigin/genetics , COVID-19/pathology , COVID-19/prevention & control , COVID-19/virology , Caco-2 Cells , Cell Line , Chlorocebus aethiops , Hep G2 Cells , Host-Pathogen Interactions , Humans , Molecular Targeted Therapy , RNA Interference/physiology , RNA, Small Interfering/pharmacology , RNA, Small Interfering/therapeutic use , Receptors, Virus/metabolism , Receptors, Virus/physiology , SARS-CoV-2/metabolism , Vero Cells , Viral Tropism/physiology
2.
FEBS J ; 287(17): 3677-3680, 2020 09.
Article in English | MEDLINE | ID: covidwho-960856

ABSTRACT

Coronavirus disease 2019 (COVID-19), the highly contagious illness caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread across the globe, becoming one of the most challenging public health crisis of our times. SARS-CoV-2 can cause severe disease associated with multiple organ damage. Cancer patients have a higher risk of SARS-CoV-2 infection and death. While the virus uses angiotensin-converting enzyme 2 (ACE2) as the primary entry receptor, the recent experimental and clinical findings suggest that some tumor markers, including CD147 (basigin), can provide an additional entry for SARS-CoV-2 infection through binding to the viral spike (S) protein. In the absence of specific viral drugs, blocking of CD147 might be a way to prevent virus invasion. Identifying other target proteins is of high importance as targeting the alternative receptors for SARS-CoV-2 might open up a promising avenue for the treatment of COVID-19 patients, including those who have cancer.


Subject(s)
Antineoplastic Agents, Immunological/therapeutic use , Basigin/antagonists & inhibitors , Biomarkers, Tumor/antagonists & inhibitors , COVID-19/drug therapy , Neoplasms/drug therapy , Spike Glycoprotein, Coronavirus/antagonists & inhibitors , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Basigin/genetics , Basigin/immunology , Biomarkers, Tumor/genetics , Biomarkers, Tumor/immunology , COVID-19/genetics , COVID-19/immunology , COVID-19/virology , Clinical Trials as Topic , Host-Pathogen Interactions/drug effects , Host-Pathogen Interactions/genetics , Host-Pathogen Interactions/immunology , Humans , Neoplasms/genetics , Neoplasms/immunology , Neoplasms/virology , Protein Binding , Receptors, Virus/genetics , Receptors, Virus/metabolism , SARS-CoV-2/drug effects , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Severity of Illness Index , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism
3.
Front Immunol ; 11: 570927, 2020.
Article in English | MEDLINE | ID: covidwho-895301

ABSTRACT

The emergence and rapid spread of SARS-CoV-2 in December 2019 has brought the world to a standstill. While less pathogenic than the 2002-2003 SARS-CoV, this novel betacoronavirus presents a global threat due to its high transmission rate, ability to invade multiple tissues, and ability to trigger immunological hyperactivation. The identification of the animal reservoir and intermediate host were important steps toward slowing the spread of disease, and its genetic similarity to SARS-CoV has helped to determine pathogenesis and direct treatment strategies. The exponential increase in cases has necessitated fast and reliable testing procedures. Although RT-PCR remains the gold standard, it is a time-consuming procedure, paving the way for newer techniques such as serologic tests and enzyme immunoassays. Various clinical trials using broad antiviral agents in addition to novel medications have produced controversial results; however, the advancement of immunotherapy, particularly monoclonal antibodies and immune modulators is showing great promise in clinical trials. Non-orthodox medications such as anti-malarials have been tested in multiple institutions but definitive conclusions are yet to be made. Adjuvant therapies have also proven to be effective in decreasing mortality in the disease course. While no formal guidelines have been established, the multitude of ongoing clinical trials as a result of unprecedented access to research data brings us closer to halting the SARS-CoV-2 pandemic.


Subject(s)
Antiviral Agents/therapeutic use , Betacoronavirus/drug effects , Clinical Laboratory Techniques/methods , Coronavirus Infections , Pandemics , Pneumonia, Viral , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/therapeutic use , Angiotensin-Converting Enzyme 2 , Antibodies, Monoclonal/therapeutic use , Antibodies, Viral/therapeutic use , Betacoronavirus/genetics , Betacoronavirus/immunology , COVID-19 , COVID-19 Testing , Coronavirus Infections/diagnosis , Coronavirus Infections/pathology , Coronavirus Infections/therapy , Disease Reservoirs/virology , Drug Repositioning/methods , Humans , Immunoenzyme Techniques , Immunotherapy , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/diagnosis , Pneumonia, Viral/pathology , Pneumonia, Viral/therapy , Receptors, Virus/metabolism , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2 , Serologic Tests/methods , Spike Glycoprotein, Coronavirus/metabolism
4.
Med Hypotheses ; 143: 110089, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-647513

ABSTRACT

Extracellular matrix metalloproteinase inducer (EMMPRIN), which is also called BASIGIN/CD147, is a cell surface glycoprotein that belongs to the immunoglobulin superfamily and plays a significant role in intercellular recognition in immunology, cellular differentiation and development. Apart from ACE-2, recently EMMPRIN, has been regarded as a target for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) attachment and entry into the host cell. Since one of the routes of entry for the virus is the oral cavity, it becomes imperative to percept oral comorbidities such oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMDs) in terms of EMMPRIN as a target for SARS-CoV-2. In the present paper, it is proposed that OSCC, by the virtue of upregulation of EMMPRIN expression, increases the susceptibility to coronavirus disease (COVID-19). In turn, COVID-19 in OSCC patients causes exhaustion of EMMPRIN receptor due to binding with 'S' receptor leading to a downregulation of related carcinogenesis events. We proposed that in the ACE-2 depleted situation in OSCC, EMMPRIN receptor might get high jacked by the COVID-19 virus for the entry into the host cells. Apart from the anti-monoclonal antibody, it is recommended to explore the use of grape seed and skin containing mouthwash as an adjunct, which could also have anti EMMPRIN effects in patients with OSCC and OPMDs.


Subject(s)
Basigin/metabolism , Coronavirus Infections/metabolism , Gene Expression Regulation, Neoplastic , Mouth Neoplasms/metabolism , Pneumonia, Viral/metabolism , Angiotensin-Converting Enzyme 2 , Antibodies, Monoclonal , Betacoronavirus , COVID-19 , Carcinoma, Squamous Cell/complications , Carcinoma, Squamous Cell/metabolism , Coronavirus Infections/complications , Disease Susceptibility , Grape Seed Extract , Humans , Mouth Neoplasms/complications , Mouthwashes , Pandemics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/complications , Protein Binding , SARS-CoV-2
5.
Stem Cell Rev Rep ; 16(3): 434-440, 2020 06.
Article in English | MEDLINE | ID: covidwho-71853

ABSTRACT

The expressive number of deaths and confirmed cases of SARS-CoV-2 call for an urgent demand of effective and available drugs for COVID-19 treatment. CD147, a receptor on host cells, is a novel route for SARS-CoV-2 invasion. Thus, drugs that interfere in the spike protein/CD147 interaction or CD147 expression may inhibit viral invasion and dissemination among other cells, including in progenitor/stem cells. Studies suggest beneficial effects of azithromycin in reducing viral load of hospitalized patients, possibly interfering with ligand/CD147 receptor interactions; however, its possible effects on SARS-CoV-2 invasion has not yet been evaluated. In addition to the possible effect in invasion, azithromycin decreases the expression of some metalloproteinases (downstream to CD147), induces anti-viral responses in primary human bronchial epithelial infected with rhinovirus, decreasing viral replication and release. Moreover, resident lung progenitor/stem are extensively differentiated into myofibroblasts during pulmonary fibrosis, a complication observed in COVID-19 patients. This process, and the possible direct viral invasion of progenitor/stem cells via CD147 or ACE2, could result in the decline of these cellular stocks and failing lung repair. Clinical tests with allogeneic MSCs from healthy individuals are underway to enhance endogenous lung repair and suppress inflammation.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Azithromycin/therapeutic use , Basigin/genetics , Betacoronavirus/drug effects , Coronavirus Infections/therapy , Pandemics , Pneumonia, Viral/therapy , Spike Glycoprotein, Coronavirus/genetics , Stem Cell Transplantation , Angiotensin-Converting Enzyme 2 , B-Lymphocytes/drug effects , B-Lymphocytes/immunology , B-Lymphocytes/virology , Basigin/antagonists & inhibitors , Basigin/immunology , Betacoronavirus/metabolism , Betacoronavirus/pathogenicity , COVID-19 , Clinical Trials as Topic , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Coronavirus Infections/virology , Gene Expression , Host-Pathogen Interactions/drug effects , Host-Pathogen Interactions/immunology , Humans , Lung/immunology , Lung/virology , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/immunology , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Protein Binding/drug effects , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/antagonists & inhibitors , Spike Glycoprotein, Coronavirus/immunology , Stem Cells/drug effects , Stem Cells/immunology , Stem Cells/virology , T-Lymphocytes/drug effects , T-Lymphocytes/immunology , T-Lymphocytes/virology , Viral Load/drug effects
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