AC-73 and Syrosingopine Inhibit SARS-CoV-2 Entry into Megakaryocytes by Targeting CD147 and MCT4
Coagulation disorders are described in COVID-19 and long COVID patients. In particular, SARS-CoV-2 infection in megakaryocytes, which are precursors of platelets involved in thrombotic events in COVID-19, long COVID and, in rare cases, in vaccinated individuals, requires further investigation, parti...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-01-01
|
| Series: | Viruses |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4915/16/1/82 |
| _version_ | 1797342402057338880 |
|---|---|
| author | Isabella Spinello Ernestina Saulle Maria Teresa Quaranta Elvira Pelosi Germana Castelli Annamaria Cerio Luca Pasquini Ornella Morsilli Maria Luisa Dupuis Catherine Labbaye |
| author_facet | Isabella Spinello Ernestina Saulle Maria Teresa Quaranta Elvira Pelosi Germana Castelli Annamaria Cerio Luca Pasquini Ornella Morsilli Maria Luisa Dupuis Catherine Labbaye |
| author_sort | Isabella Spinello |
| collection | DOAJ |
| description | Coagulation disorders are described in COVID-19 and long COVID patients. In particular, SARS-CoV-2 infection in megakaryocytes, which are precursors of platelets involved in thrombotic events in COVID-19, long COVID and, in rare cases, in vaccinated individuals, requires further investigation, particularly with the emergence of new SARS-CoV-2 variants. CD147, involved in the regulation of inflammation and required to fight virus infection, can facilitate SARS-CoV-2 entry into megakaryocytes. MCT4, a co-binding protein of CD147 and a key player in the glycolytic metabolism, could also play a role in SARS-CoV-2 infection. Here, we investigated the susceptibility of megakaryocytes to SARS-CoV-2 infection via CD147 and MCT4. We performed infection of Dami cells and human CD34<sup>+</sup> hematopoietic progenitor cells induced to megakaryocytic differentiation with SARS-CoV-2 pseudovirus in the presence of AC-73 and syrosingopine, respective inhibitors of CD147 and MCT4 and inducers of autophagy, a process essential in megakaryocyte differentiation. Both AC-73 and syrosingopine enhance autophagy during differentiation but only AC-73 enhances megakaryocytic maturation. Importantly, we found that AC-73 or syrosingopine significantly inhibits SARS-CoV-2 infection of megakaryocytes. Altogether, our data indicate AC-73 and syrosingopine as inhibitors of SARS-CoV-2 infection via CD147 and MCT4 that can be used to prevent SARS-CoV-2 binding and entry into megakaryocytes, which are precursors of platelets involved in COVID-19-associated coagulopathy. |
| first_indexed | 2024-03-08T10:32:46Z |
| format | Article |
| id | doaj.art-b97753985448449cbe0f0ff4f98f5fd4 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-08T10:32:46Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-b97753985448449cbe0f0ff4f98f5fd42024-01-26T18:48:04ZengMDPI AGViruses1999-49152024-01-011618210.3390/v16010082AC-73 and Syrosingopine Inhibit SARS-CoV-2 Entry into Megakaryocytes by Targeting CD147 and MCT4Isabella Spinello0Ernestina Saulle1Maria Teresa Quaranta2Elvira Pelosi3Germana Castelli4Annamaria Cerio5Luca Pasquini6Ornella Morsilli7Maria Luisa Dupuis8Catherine Labbaye9National Center for Drug Research and Evaluation, Istituto Superiore di Sanità, 00161 Rome, ItalyNational Center for Drug Research and Evaluation, Istituto Superiore di Sanità, 00161 Rome, ItalyNational Center for Drug Research and Evaluation, Istituto Superiore di Sanità, 00161 Rome, ItalyDepartment of Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, ItalyDepartment of Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, ItalyDepartment of Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, ItalyCore Facilities, Istituto Superiore di Sanità, 00161 Rome, ItalyDepartment of Cardiovascular, Endocrine-Metabolic Diseases and Ageing, Istituto Superiore di Sanità, 00161 Rome, ItalyNational Center for Drug Research and Evaluation, Istituto Superiore di Sanità, 00161 Rome, ItalyNational Center for Drug Research and Evaluation, Istituto Superiore di Sanità, 00161 Rome, ItalyCoagulation disorders are described in COVID-19 and long COVID patients. In particular, SARS-CoV-2 infection in megakaryocytes, which are precursors of platelets involved in thrombotic events in COVID-19, long COVID and, in rare cases, in vaccinated individuals, requires further investigation, particularly with the emergence of new SARS-CoV-2 variants. CD147, involved in the regulation of inflammation and required to fight virus infection, can facilitate SARS-CoV-2 entry into megakaryocytes. MCT4, a co-binding protein of CD147 and a key player in the glycolytic metabolism, could also play a role in SARS-CoV-2 infection. Here, we investigated the susceptibility of megakaryocytes to SARS-CoV-2 infection via CD147 and MCT4. We performed infection of Dami cells and human CD34<sup>+</sup> hematopoietic progenitor cells induced to megakaryocytic differentiation with SARS-CoV-2 pseudovirus in the presence of AC-73 and syrosingopine, respective inhibitors of CD147 and MCT4 and inducers of autophagy, a process essential in megakaryocyte differentiation. Both AC-73 and syrosingopine enhance autophagy during differentiation but only AC-73 enhances megakaryocytic maturation. Importantly, we found that AC-73 or syrosingopine significantly inhibits SARS-CoV-2 infection of megakaryocytes. Altogether, our data indicate AC-73 and syrosingopine as inhibitors of SARS-CoV-2 infection via CD147 and MCT4 that can be used to prevent SARS-CoV-2 binding and entry into megakaryocytes, which are precursors of platelets involved in COVID-19-associated coagulopathy.https://www.mdpi.com/1999-4915/16/1/82SARS-CoV-2coagulation disordersmegakaryocytesCD147MCT4 |
| spellingShingle | Isabella Spinello Ernestina Saulle Maria Teresa Quaranta Elvira Pelosi Germana Castelli Annamaria Cerio Luca Pasquini Ornella Morsilli Maria Luisa Dupuis Catherine Labbaye AC-73 and Syrosingopine Inhibit SARS-CoV-2 Entry into Megakaryocytes by Targeting CD147 and MCT4 Viruses SARS-CoV-2 coagulation disorders megakaryocytes CD147 MCT4 |
| title | AC-73 and Syrosingopine Inhibit SARS-CoV-2 Entry into Megakaryocytes by Targeting CD147 and MCT4 |
| title_full | AC-73 and Syrosingopine Inhibit SARS-CoV-2 Entry into Megakaryocytes by Targeting CD147 and MCT4 |
| title_fullStr | AC-73 and Syrosingopine Inhibit SARS-CoV-2 Entry into Megakaryocytes by Targeting CD147 and MCT4 |
| title_full_unstemmed | AC-73 and Syrosingopine Inhibit SARS-CoV-2 Entry into Megakaryocytes by Targeting CD147 and MCT4 |
| title_short | AC-73 and Syrosingopine Inhibit SARS-CoV-2 Entry into Megakaryocytes by Targeting CD147 and MCT4 |
| title_sort | ac 73 and syrosingopine inhibit sars cov 2 entry into megakaryocytes by targeting cd147 and mct4 |
| topic | SARS-CoV-2 coagulation disorders megakaryocytes CD147 MCT4 |
| url | https://www.mdpi.com/1999-4915/16/1/82 |
| work_keys_str_mv | AT isabellaspinello ac73andsyrosingopineinhibitsarscov2entryintomegakaryocytesbytargetingcd147andmct4 AT ernestinasaulle ac73andsyrosingopineinhibitsarscov2entryintomegakaryocytesbytargetingcd147andmct4 AT mariateresaquaranta ac73andsyrosingopineinhibitsarscov2entryintomegakaryocytesbytargetingcd147andmct4 AT elvirapelosi ac73andsyrosingopineinhibitsarscov2entryintomegakaryocytesbytargetingcd147andmct4 AT germanacastelli ac73andsyrosingopineinhibitsarscov2entryintomegakaryocytesbytargetingcd147andmct4 AT annamariacerio ac73andsyrosingopineinhibitsarscov2entryintomegakaryocytesbytargetingcd147andmct4 AT lucapasquini ac73andsyrosingopineinhibitsarscov2entryintomegakaryocytesbytargetingcd147andmct4 AT ornellamorsilli ac73andsyrosingopineinhibitsarscov2entryintomegakaryocytesbytargetingcd147andmct4 AT marialuisadupuis ac73andsyrosingopineinhibitsarscov2entryintomegakaryocytesbytargetingcd147andmct4 AT catherinelabbaye ac73andsyrosingopineinhibitsarscov2entryintomegakaryocytesbytargetingcd147andmct4 |