ArticleInternational journal of molecular sciences2021
SARS-CoV-2 Proteins Bind to Hemoglobin and Its Metabolites.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 59 citations in OpenAlex.
- Comparative proteomics of human naso-oropharyngeal swabs from COVID19 patients for identification of potential biomarker candidates.Biochemistry and biophysics reports · 2026Article
- Transmissible Gastroenteritis Virus Binding to Red Blood Cells Disrupts Iron Homeostasis and Promotes Viral Infection.Veterinary sciences · 2026Article
- SARS-CoV-2 spike S1-mediated HIF-2α activation in retinal endothelial cells suggests a mechanism contributing to post-COVID endothelial dysfunction.Frontiers in immunology · 2026Article
- Fragments of viral surface proteins modulate innate immune responses via formyl peptide receptors.iScience · 2025Article
- Hemoglobin Variants as Targets for Stabilizing Drugs.Molecules (Basel, Switzerland) · 2025Review
- Proteomic analysis of lung responses to SARS-CoV-2 infection in aged non-human primates: clinical and research relevance.GeroScience · 2024Article
- Blood matters: the hematological signatures of Coronavirus infection.Cell death & disease · 2024Article
- Artemisinin-resistant Plasmodium falciparum Kelch13 mutant proteins display reduced heme-binding affinity and decreased artemisinin activation.Communications biology · 2024Article
- Targeting the High-Density Lipoprotein Proteome for the Treatment of Post-Acute Sequelae of SARS-CoV-2.International journal of molecular sciences · 2024Article
- Precision nutrition to reset virus-induced human metabolic reprogramming and dysregulation (HMRD) in long-COVID.NPJ science of food · 2024Review
- SARS-CoV-2 Infection and Anemia-A Focus on RBC Deformability and Membrane Proteomics-Integrated Observational Prospective Study.Microorganisms · 2024Article
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- The Mechanisms of Ferroptosis Under Hypoxia.Cellular and molecular neurobiology · 2023Review
- Long COVID manifests with T cell dysregulation, inflammation, and an uncoordinated adaptive immune response to SARS-CoV-2.bioRxiv : the preprint server for biology · 2023Article
- Endogenous piRNAs Can Interact with the Omicron Variant of the SARS-CoV-2 Genome.Current issues in molecular biology · 2023Article
- Binding of SARS-CoV-2 Structural Proteins to Hemoglobin and Myoglobin Studied by SPR and DR LPG.Sensors (Basel, Switzerland) · 2023Article
- Hematological alterations associated with long COVID-19.Frontiers in physiology · 2023Review
- Association of iron-related biomarkers with severity and mortality in COVID-19 patients.Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) · 2022Article
- Neuropeptides, New Ligands of SARS-CoV-2 Nucleoprotein, a Potential Link between Replication, Inflammation and Neurotransmission.Molecules (Basel, Switzerland) · 2022Article
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
(1) Background: coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been linked to hematological dysfunctions, but there are little experimental data that explain this. Spike (S) and Nucleoprotein (N) proteins have been putatively associated with these dysfunctions. In this work, we analyzed the recruitment of hemoglobin (Hb) and other metabolites (hemin and protoporphyrin IX-PpIX) by SARS-Cov2 proteins using different approaches. (2) Methods: shotgun proteomics (LC-MS/MS) after affinity column adsorption identified hemin-binding SARS-CoV-2 proteins. The parallel synthesis of the peptides technique was used to study the interaction of the receptor bind domain (RBD) and N-terminal domain (NTD) of the S protein with Hb and in silico analysis to identify the binding motifs of the N protein. The plaque assay was used to investigate the inhibitory effect of Hb and the metabolites hemin and PpIX on virus adsorption and replication in Vero cells. (3) Results: the proteomic analysis by LC-MS/MS identified the S, N, M, Nsp3, and Nsp7 as putative hemin-binding proteins. Six short sequences in the RBD and 11 in the NTD of the spike were identified by microarray of peptides to interact with Hb and tree motifs in the N protein by in silico analysis to bind with heme. An inhibitory effect in vitro of Hb, hemin, and PpIX at different levels was observed. Strikingly, free Hb at 1mM suppressed viral replication (99%), and its interaction with SARS-CoV-2 was localized into the RBD region of the spike protein. (4) Conclusions: in this study, we identified that (at least) five proteins (S, N, M, Nsp3, and Nsp7) of SARS-CoV-2 recruit Hb/metabolites. The motifs of the RDB of SARS-CoV-2 spike, which binds Hb, and the sites of the heme bind-N protein were disclosed. In addition, these compounds and PpIX block the virus's adsorption and replication. Furthermore, we also identified heme-binding motifs and interaction with hemin in N protein and other structural (S and M) and non-structural (Nsp3 and Nsp7) proteins.
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