COVID-19 News: Study Validates That SARS-CoV-2 Structural Proteins Binds To Hemoglobin And Myoglobin Causing Hemoglobin And Iron Dysmetabolism!
: Researchers from the Bulgarian Academy of Sciences (BAS)-Bulgaria, National Center of Infectious and Parasitic Diseases- Bulgaria and Université du Québec en Outaouais-Canada in a news study using surface plasmon resonance (SPR) and double resonance long period grating (DR LPG) techniques have validated that SARS-CoV-2 structural proteins binds to hemoglobin and myoglobin causing hemoglobin and iron dysmetabolism!
The study has a variety of implications in terms of conditions seen in severe disease conditions and also in terms of long COVID for all who have been exposed to the SARS-CoV-2 virus irrespective if they were asymptomatic or symptomatic.
As early as April 2020, Thailand Medical News had written COVID-19 News
coverages on how the SARS-CoV-2 affects hemoglobin but that time, American-based ‘bastard’ fact checkers that had no medical background employed by Facebook claimed that these studies and our coverages were fake news!
Lots of studies have since emerged to add to these early findings along with many others like this current study that further validates that SARS-CoV-2 does bind to hemoglobin and causing it to become dysfunctional.
In fact, studies also show that hematological changes due to SARS-CoV-2 infections persist in Long COVID individuals for as long as 985 days after so called recovery!
COVID-19, caused by the SARS-CoV-2 virus, primarily affects the lungs and has been observed to result in hematological dysfunctions.
The exact origin of the initial pathological viral process remains unclear, with hypotheses suggesting it may begin in the lungs, ultimately leading to generalized hypoxia and iron dysmetabolism. Hemoglobin and iron dysmetabolism are considered potential driving forces behind multiorgan disease and hypoxia associated with COVID-19.
Early clinical observations and theoretical modeling have predicted that motifs from SARS-CoV-2 structural proteins could bind to porphyrin, which plays a critical role in heme metabolism. However, there is a significant lack of experimental data to support these claims.
In order to address this gap, researchers employed surface plasmon resonance (SPR) and double resonance long period grating (DR LPG) methods to investigate the binding of SARS-CoV-2 S/N protein and the receptor-binding domain (RBD) to hemoglobin (Hb) and myoglobin (Mb).
SPR transducers were functionalized with Hb and Mb, while LPG transducers were functionalized only with Hb. Ligands were deposited using the matrix-assisted laser evaporation (MAPLE) method, ensuring maximum interaction specificity.
The experiments demonstrated S/N protein binding to both Hb and Mb and RBD binding to Hb.
Additionally, they revealed that chemically-inactivated virus-like particles (VLPs) interact with Hb.
The binding activity of S/N and RBD proteins was assessed, and it was discovered that protein binding completely inhibited heme functionality.
The observed N protein binding to Hb/Mb is the first experimental evidence supporting theoretical predictions, suggesting an additional function for this protein beyond RNA binding.
The lower RBD binding activity indicates that other functional groups of the S protein may be involved in the interaction. The high-affinity binding of these proteins to Hb presents an excellent opportunity to evaluate the effectiveness of inhibitors targeting S/N proteins.
To further investigate the binding mechanisms of SARS-CoV-2 S/N structural proteins and RBD protein, as well as VLPs to Hb/Mb, researchers utilized SPR and DR LPG sensing platforms.
These platforms are highly sensitive to changes in the surrounding refractive index and have been successfully applied to SARS-CoV-2 diagnosis, glucose sensing, and bacteria and virus detection.
The study aimed to provide additional experimental data to confirm the results previously obtained by biochemical methods, utilizing physical detection methods. The research was based on registering physical phenomena resulting from the direct molecular interactions of S/N proteins, RBD proteins, and VLPs with Hb/Mb on SPR and DR LPG transducers. Obtaining consistent experimental results from both detection systems would strengthen the validity of these complex experiments.
The experimental results presented in this study indicate that SARS-CoV-2 structural proteins and the virus itself actively bind to heme, completely inhibiting its function. This binding activity contributes to poor clinical outcomes, as heme plays a vital role in numerous biological processes, including oxygen transport and metabolism. Abnormalities in heme metabolism can be observed before the acute phase of infection due to the higher binding affinity to Hb compared to monoclonal antibodies.
While the reactions studied have low specificity and cannot be used for diagnosing infection from clinical samples, their high affinity makes them ideal for evaluating the effectiveness of inhibitors targeting S/N proteins. Numerous potential antibodies directed to S-RBD, S-NTD, and N-NTD have been identified, and an evaluation approach using SPR and DR LPG sensing platforms can help prevent disappointments in clinical trials. The real-time monitoring of biomolecular interactions performed by the DR LPG sensing platform offers significant advantages in such studies.
The data reported in this study demonstrate that SPR and DR LPG can detect proteins with a limit of detection reaching several tens of femtomolar (fM). This is in contrast to the 130 fM achieved by SPR detection based on antibody-antigen interaction. This difference can be attributed to the higher binding affinity of Hb/Mb. The detectable levels achieved in different sensing assays and the consistent results obtained by the demonstrated biosensor platforms validate the protocols applied for immobilization, bioactive material handling, and measurement procedures.
In summary, this study provides valuable experimental data on the binding mechanisms of SARS-CoV-2 structural proteins to hemoglobin and myoglobin. The findings not only support theoretical predictions but also offer insights into the biological role of proteins and the clinical manifestation of viral disease. Moreover, they shed light on the potential for early diagnosis of infection. By employing SPR and DR LPG techniques, the research confirms previously obtained biochemical results and highlights the importance of establishing a standardized protocol for ligand immobilization, bioactive substance manipulation, and measurement procedures.
The implications of these findings are far-reaching, as they may inform the development of novel therapeutics, diagnostics, and prevention strategies for COVID-19. By understanding the molecular interactions between SARS-CoV-2 proteins and hemoglobin/myoglobin, researchers can better target pathophysiological pathways and design more effective antibodies, vaccines, and inhibitors.
Furthermore, the success of SPR and DR LPG sensing platforms in studying the binding behavior of SARS-CoV-2 proteins indicates their potential application in future research on other viruses and pathogens. As the understanding of SARS-CoV-2 and its interactions with host proteins continues to evolve, these experimental techniques may play a crucial role in unraveling the complex interplay between viral proteins and human biology, ultimately contributing to the global effort to combat COVID-19 and other infectious diseases.
The study findings were published on in the peer reviewed journal: Sensors.
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