Interactomic Analyses and a Reverse Engineering Study Identify Specific Functional Activities of One-to-One Interactions of the S1 Subunit of the SARS-CoV-2 Spike Protein with the Human Proteome
The S1 subunit of SARS-CoV-2 Spike is crucial for ACE2 recognition and viral entry into human cells. It has been found in the blood of COVID-19 patients and vaccinated individuals. Using BioGRID, I identified 146 significant human proteins that interact with S1. I then created an interactome model t...
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2024-12-01
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| author | Giovanni Colonna |
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| description | The S1 subunit of SARS-CoV-2 Spike is crucial for ACE2 recognition and viral entry into human cells. It has been found in the blood of COVID-19 patients and vaccinated individuals. Using BioGRID, I identified 146 significant human proteins that interact with S1. I then created an interactome model that made it easier to study functional activities. Through a reverse engineering approach, 27 specific one-to-one interactions of S1 with the human proteome were selected. S1 interacts in this manner independently from the biological context in which it operates, be it infection or vaccination. Instead, when it works together with viral proteins, they carry out multiple attacks on single human proteins, showing a different functional engagement. The functional implications and tropism of the virus for human organs/tissues were studied using Cytoscape. The nervous system, liver, blood, and lungs are among the most affected. As a single protein, S1 operates in a complex metabolic landscape which includes 2557 Biological Processes (GO), much more than the 1430 terms controlled when operating in a group. A Data Merging approach shows that the total proteins involved by S1 in the cell are over 60,000 with an average involvement per single biological process of 26.19. However, many human proteins become entangled in over 100 different biological activities each. Clustering analysis showed significant activations of many molecular mechanisms, like those related to hepatitis B infections. This suggests a potential involvement in carcinogenesis, based on a viral strategy that uses the ubiquitin system to impair the tumor suppressor and antiviral functions of TP53, as well as the role of RPS27A in protein turnover and cellular stress responses. |
| format | Article |
| id | doaj-art-7773635b15f94874856afc347777eace |
| institution | Kabale University |
| issn | 2218-273X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
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| series | Biomolecules |
| spelling | doaj-art-7773635b15f94874856afc347777eace2024-12-27T14:13:46ZengMDPI AGBiomolecules2218-273X2024-12-011412154910.3390/biom14121549Interactomic Analyses and a Reverse Engineering Study Identify Specific Functional Activities of One-to-One Interactions of the S1 Subunit of the SARS-CoV-2 Spike Protein with the Human ProteomeGiovanni Colonna0Unit of Medical Informatics—AOU Luigi Vanvitelli, University of Campania, 80138 Naples, ItalyThe S1 subunit of SARS-CoV-2 Spike is crucial for ACE2 recognition and viral entry into human cells. It has been found in the blood of COVID-19 patients and vaccinated individuals. Using BioGRID, I identified 146 significant human proteins that interact with S1. I then created an interactome model that made it easier to study functional activities. Through a reverse engineering approach, 27 specific one-to-one interactions of S1 with the human proteome were selected. S1 interacts in this manner independently from the biological context in which it operates, be it infection or vaccination. Instead, when it works together with viral proteins, they carry out multiple attacks on single human proteins, showing a different functional engagement. The functional implications and tropism of the virus for human organs/tissues were studied using Cytoscape. The nervous system, liver, blood, and lungs are among the most affected. As a single protein, S1 operates in a complex metabolic landscape which includes 2557 Biological Processes (GO), much more than the 1430 terms controlled when operating in a group. A Data Merging approach shows that the total proteins involved by S1 in the cell are over 60,000 with an average involvement per single biological process of 26.19. However, many human proteins become entangled in over 100 different biological activities each. Clustering analysis showed significant activations of many molecular mechanisms, like those related to hepatitis B infections. This suggests a potential involvement in carcinogenesis, based on a viral strategy that uses the ubiquitin system to impair the tumor suppressor and antiviral functions of TP53, as well as the role of RPS27A in protein turnover and cellular stress responses.https://www.mdpi.com/2218-273X/14/12/1549SARS-CoV-2S1 subunit of the SARS-CoV-2 Spike proteinSARS-CoV-2 and cancerone-to-one interactions in COVID-19 infectionTP53 and RSP27Along COVID-19 |
| spellingShingle | Giovanni Colonna Interactomic Analyses and a Reverse Engineering Study Identify Specific Functional Activities of One-to-One Interactions of the S1 Subunit of the SARS-CoV-2 Spike Protein with the Human Proteome Biomolecules SARS-CoV-2 S1 subunit of the SARS-CoV-2 Spike protein SARS-CoV-2 and cancer one-to-one interactions in COVID-19 infection TP53 and RSP27A long COVID-19 |
| title | Interactomic Analyses and a Reverse Engineering Study Identify Specific Functional Activities of One-to-One Interactions of the S1 Subunit of the SARS-CoV-2 Spike Protein with the Human Proteome |
| title_full | Interactomic Analyses and a Reverse Engineering Study Identify Specific Functional Activities of One-to-One Interactions of the S1 Subunit of the SARS-CoV-2 Spike Protein with the Human Proteome |
| title_fullStr | Interactomic Analyses and a Reverse Engineering Study Identify Specific Functional Activities of One-to-One Interactions of the S1 Subunit of the SARS-CoV-2 Spike Protein with the Human Proteome |
| title_full_unstemmed | Interactomic Analyses and a Reverse Engineering Study Identify Specific Functional Activities of One-to-One Interactions of the S1 Subunit of the SARS-CoV-2 Spike Protein with the Human Proteome |
| title_short | Interactomic Analyses and a Reverse Engineering Study Identify Specific Functional Activities of One-to-One Interactions of the S1 Subunit of the SARS-CoV-2 Spike Protein with the Human Proteome |
| title_sort | interactomic analyses and a reverse engineering study identify specific functional activities of one to one interactions of the s1 subunit of the sars cov 2 spike protein with the human proteome |
| topic | SARS-CoV-2 S1 subunit of the SARS-CoV-2 Spike protein SARS-CoV-2 and cancer one-to-one interactions in COVID-19 infection TP53 and RSP27A long COVID-19 |
| url | https://www.mdpi.com/2218-273X/14/12/1549 |
| work_keys_str_mv | AT giovannicolonna interactomicanalysesandareverseengineeringstudyidentifyspecificfunctionalactivitiesofonetooneinteractionsofthes1subunitofthesarscov2spikeproteinwiththehumanproteome |