Intrinsic factors behind long COVID: exploring the role of nucleocapsid protein in thrombosis
COVID-19, caused by the SARS-CoV-2, poses significant global health challenges. A key player in its pathogenesis is the nucleocapsid protein (NP), which is crucial for viral replication and assembly. While NPs from other coronaviruses, such as SARS-CoV and MERS-CoV, are known to increase inflammatio...
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PeerJ Inc.
2025-05-01
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| author | Ahmed Eltayeb Muhamed Adilović Maryam Golzardi Altijana Hromić-Jahjefendić Alberto Rubio-Casillas Vladimir N. Uversky Elrashdy M. Redwan |
| author_facet | Ahmed Eltayeb Muhamed Adilović Maryam Golzardi Altijana Hromić-Jahjefendić Alberto Rubio-Casillas Vladimir N. Uversky Elrashdy M. Redwan |
| author_sort | Ahmed Eltayeb |
| collection | DOAJ |
| description | COVID-19, caused by the SARS-CoV-2, poses significant global health challenges. A key player in its pathogenesis is the nucleocapsid protein (NP), which is crucial for viral replication and assembly. While NPs from other coronaviruses, such as SARS-CoV and MERS-CoV, are known to increase inflammation and cause acute lung injury, the specific effects of the SARS-CoV-2 NP on host cells remain largely unexplored. Recent findings suggest that the NP acts as a pathogen-associated molecular pattern (PAMP) that binds to Toll-like receptor 2 (TLR2), activating NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) and MAPK (mitogen-activated protein kinase) signaling pathways. This activation is particularly pronounced in severe COVID-19 cases, leading to elevated levels of soluble ICAM-1 (intercellular adhesion molecule 1) and VCAM-1 (vascular cell adhesion molecule 1), which contribute to endothelial dysfunction and multiorgan damage. Furthermore, the NP is implicated in hyperinflammation and thrombosis—key factors in COVID-19 severity and long COVID. Its potential to bind with MASP-2 (mannan-binding lectin serine protease 2) may also be linked to persistent symptoms in long COVID patients. Understanding these mechanisms, particularly the role of the NP in thrombosis, is essential for developing targeted therapies to manage both acute and chronic effects of COVID-19 effectively. This comprehensive review aims to elucidate the multifaceted roles of the NP, highlighting its contributions to viral pathogenesis, immune evasion, and the exacerbation of thrombotic events, thereby providing insights into potential therapeutic targets for mitigating the severe and long-term impacts of COVID-19. |
| format | Article |
| id | doaj-art-09a84fa7ec9a4bfabd53a82fb29668ca |
| institution | OA Journals |
| issn | 2167-8359 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | PeerJ Inc. |
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| series | PeerJ |
| spelling | doaj-art-09a84fa7ec9a4bfabd53a82fb29668ca2025-08-20T02:25:48ZengPeerJ Inc.PeerJ2167-83592025-05-0113e1942910.7717/peerj.19429Intrinsic factors behind long COVID: exploring the role of nucleocapsid protein in thrombosisAhmed Eltayeb0Muhamed Adilović1Maryam Golzardi2Altijana Hromić-Jahjefendić3Alberto Rubio-Casillas4Vladimir N. Uversky5Elrashdy M. Redwan6Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah, Saudi ArabiaDepartment of Genetics and Bioengineering, Faculty of Engineering and Natural Sciences, International University of Sarajevo, Sarajevo, Bosnia and HerzegovinaDepartment of Genetics and Bioengineering, Faculty of Engineering and Natural Sciences, International University of Sarajevo, Sarajevo, Bosnia and HerzegovinaDepartment of Genetics and Bioengineering, Faculty of Engineering and Natural Sciences, International University of Sarajevo, Sarajevo, Bosnia and HerzegovinaAutlan Regional Hospital, Jalisco Health Services, Jalisco, MexicoDepartment of Molecular Medicine and USF Health Byrd Alzheimer’s Research Institute, Morsani College of Medicine, University of South Florida, Tampa, FL, United States of AmericaDepartment of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah, Saudi ArabiaCOVID-19, caused by the SARS-CoV-2, poses significant global health challenges. A key player in its pathogenesis is the nucleocapsid protein (NP), which is crucial for viral replication and assembly. While NPs from other coronaviruses, such as SARS-CoV and MERS-CoV, are known to increase inflammation and cause acute lung injury, the specific effects of the SARS-CoV-2 NP on host cells remain largely unexplored. Recent findings suggest that the NP acts as a pathogen-associated molecular pattern (PAMP) that binds to Toll-like receptor 2 (TLR2), activating NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) and MAPK (mitogen-activated protein kinase) signaling pathways. This activation is particularly pronounced in severe COVID-19 cases, leading to elevated levels of soluble ICAM-1 (intercellular adhesion molecule 1) and VCAM-1 (vascular cell adhesion molecule 1), which contribute to endothelial dysfunction and multiorgan damage. Furthermore, the NP is implicated in hyperinflammation and thrombosis—key factors in COVID-19 severity and long COVID. Its potential to bind with MASP-2 (mannan-binding lectin serine protease 2) may also be linked to persistent symptoms in long COVID patients. Understanding these mechanisms, particularly the role of the NP in thrombosis, is essential for developing targeted therapies to manage both acute and chronic effects of COVID-19 effectively. This comprehensive review aims to elucidate the multifaceted roles of the NP, highlighting its contributions to viral pathogenesis, immune evasion, and the exacerbation of thrombotic events, thereby providing insights into potential therapeutic targets for mitigating the severe and long-term impacts of COVID-19.https://peerj.com/articles/19429.pdfSARS-CoV-2Endothelial cellsNucleocapsid proteinLong COVIDThrombosis |
| spellingShingle | Ahmed Eltayeb Muhamed Adilović Maryam Golzardi Altijana Hromić-Jahjefendić Alberto Rubio-Casillas Vladimir N. Uversky Elrashdy M. Redwan Intrinsic factors behind long COVID: exploring the role of nucleocapsid protein in thrombosis PeerJ SARS-CoV-2 Endothelial cells Nucleocapsid protein Long COVID Thrombosis |
| title | Intrinsic factors behind long COVID: exploring the role of nucleocapsid protein in thrombosis |
| title_full | Intrinsic factors behind long COVID: exploring the role of nucleocapsid protein in thrombosis |
| title_fullStr | Intrinsic factors behind long COVID: exploring the role of nucleocapsid protein in thrombosis |
| title_full_unstemmed | Intrinsic factors behind long COVID: exploring the role of nucleocapsid protein in thrombosis |
| title_short | Intrinsic factors behind long COVID: exploring the role of nucleocapsid protein in thrombosis |
| title_sort | intrinsic factors behind long covid exploring the role of nucleocapsid protein in thrombosis |
| topic | SARS-CoV-2 Endothelial cells Nucleocapsid protein Long COVID Thrombosis |
| url | https://peerj.com/articles/19429.pdf |
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