Metal-induced oxidative stress and human plasma protein oxidation after SARS-CoV-2 infection
Abstract Pathogenesis of COVID-19 by SARS-CoV-2 resulted in a global pandemic and public health emergency in 2020. Viral infection can induce oxidative stress through reactive oxygen species (ROS). Inflammation and environmental stress are major sources of oxidative stress after infection. Micronutr...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-02-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-29119-5 |
| _version_ | 1811165936245276672 |
|---|---|
| author | Baikuntha Aryal Joseph Tillotson Kiwon Ok Andrew T. Stoltzfus Sarah L. J. Michel V. Ashutosh Rao |
| author_facet | Baikuntha Aryal Joseph Tillotson Kiwon Ok Andrew T. Stoltzfus Sarah L. J. Michel V. Ashutosh Rao |
| author_sort | Baikuntha Aryal |
| collection | DOAJ |
| description | Abstract Pathogenesis of COVID-19 by SARS-CoV-2 resulted in a global pandemic and public health emergency in 2020. Viral infection can induce oxidative stress through reactive oxygen species (ROS). Inflammation and environmental stress are major sources of oxidative stress after infection. Micronutrients such as iron, copper, zinc, and manganese play various roles in human tissues and their imbalance in blood can impact immune responses against pathogens including SARS CoV-2. We hypothesized that alteration of free metal ions during infection and metal-catalyzed oxidation plays a critical role towards pathogenesis after infection. We analyzed convalescent and hospitalized COVID-19 patient plasma using orthogonal analytical techniques to determine redox active metal concentrations, overall protein oxidation, oxidative modifications, and protein levels via proteomics to understand the consequences of metal-induced oxidative stress in COVID-19 plasma proteins. Metal analysis using ICP-MS showed significantly greater concentrations of copper in COVID-19 plasma compared to healthy controls. We demonstrate significantly greater total protein carbonylation, other oxidative modifications, and deamidation of plasma proteins in COVID-19 plasma compared to healthy controls. Proteomics analysis showed that levels of redox active proteins including hemoglobulin were elevated in COVID-19 plasma. Molecular modeling concurred with potential interactions between iron binding proteins and SARS CoV-2 surface proteins. Overall, increased levels of redox active metals and protein oxidation indicate that oxidative stress-induced protein oxidation in COVID-19 may be a consequence of the interactions of SARS-CoV-2 proteins with host cell metal binding proteins resulting in altered cellular homeostasis. |
| first_indexed | 2024-04-10T15:44:19Z |
| format | Article |
| id | doaj.art-8607a6785ee8427d8ba0c52ccb78da84 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-10T15:44:19Z |
| publishDate | 2023-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-8607a6785ee8427d8ba0c52ccb78da842023-02-12T12:12:26ZengNature PortfolioScientific Reports2045-23222023-02-0113111410.1038/s41598-023-29119-5Metal-induced oxidative stress and human plasma protein oxidation after SARS-CoV-2 infectionBaikuntha Aryal0Joseph Tillotson1Kiwon Ok2Andrew T. Stoltzfus3Sarah L. J. Michel4V. Ashutosh Rao5Laboratory of Applied Biochemistry, Division of Biotechnology Research and Review III, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug AdministrationsLaboratory of Applied Biochemistry, Division of Biotechnology Research and Review III, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug AdministrationsDepartment of Pharmaceutical Sciences, University of Maryland School of PharmacyDepartment of Pharmaceutical Sciences, University of Maryland School of PharmacyDepartment of Pharmaceutical Sciences, University of Maryland School of PharmacyLaboratory of Applied Biochemistry, Division of Biotechnology Research and Review III, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug AdministrationsAbstract Pathogenesis of COVID-19 by SARS-CoV-2 resulted in a global pandemic and public health emergency in 2020. Viral infection can induce oxidative stress through reactive oxygen species (ROS). Inflammation and environmental stress are major sources of oxidative stress after infection. Micronutrients such as iron, copper, zinc, and manganese play various roles in human tissues and their imbalance in blood can impact immune responses against pathogens including SARS CoV-2. We hypothesized that alteration of free metal ions during infection and metal-catalyzed oxidation plays a critical role towards pathogenesis after infection. We analyzed convalescent and hospitalized COVID-19 patient plasma using orthogonal analytical techniques to determine redox active metal concentrations, overall protein oxidation, oxidative modifications, and protein levels via proteomics to understand the consequences of metal-induced oxidative stress in COVID-19 plasma proteins. Metal analysis using ICP-MS showed significantly greater concentrations of copper in COVID-19 plasma compared to healthy controls. We demonstrate significantly greater total protein carbonylation, other oxidative modifications, and deamidation of plasma proteins in COVID-19 plasma compared to healthy controls. Proteomics analysis showed that levels of redox active proteins including hemoglobulin were elevated in COVID-19 plasma. Molecular modeling concurred with potential interactions between iron binding proteins and SARS CoV-2 surface proteins. Overall, increased levels of redox active metals and protein oxidation indicate that oxidative stress-induced protein oxidation in COVID-19 may be a consequence of the interactions of SARS-CoV-2 proteins with host cell metal binding proteins resulting in altered cellular homeostasis.https://doi.org/10.1038/s41598-023-29119-5 |
| spellingShingle | Baikuntha Aryal Joseph Tillotson Kiwon Ok Andrew T. Stoltzfus Sarah L. J. Michel V. Ashutosh Rao Metal-induced oxidative stress and human plasma protein oxidation after SARS-CoV-2 infection Scientific Reports |
| title | Metal-induced oxidative stress and human plasma protein oxidation after SARS-CoV-2 infection |
| title_full | Metal-induced oxidative stress and human plasma protein oxidation after SARS-CoV-2 infection |
| title_fullStr | Metal-induced oxidative stress and human plasma protein oxidation after SARS-CoV-2 infection |
| title_full_unstemmed | Metal-induced oxidative stress and human plasma protein oxidation after SARS-CoV-2 infection |
| title_short | Metal-induced oxidative stress and human plasma protein oxidation after SARS-CoV-2 infection |
| title_sort | metal induced oxidative stress and human plasma protein oxidation after sars cov 2 infection |
| url | https://doi.org/10.1038/s41598-023-29119-5 |
| work_keys_str_mv | AT baikunthaaryal metalinducedoxidativestressandhumanplasmaproteinoxidationaftersarscov2infection AT josephtillotson metalinducedoxidativestressandhumanplasmaproteinoxidationaftersarscov2infection AT kiwonok metalinducedoxidativestressandhumanplasmaproteinoxidationaftersarscov2infection AT andrewtstoltzfus metalinducedoxidativestressandhumanplasmaproteinoxidationaftersarscov2infection AT sarahljmichel metalinducedoxidativestressandhumanplasmaproteinoxidationaftersarscov2infection AT vashutoshrao metalinducedoxidativestressandhumanplasmaproteinoxidationaftersarscov2infection |