SARS-CoV-2 proteins bind heme and hemoglobin

De-Simone, Salvatore G.; Lechuga, Guilherme Curty; Souza-Silva, Franklin; Sacramento, Carolina Q.; Trugilho, Monique Ramos de Oliveira; Valente, Richard H.; Napoleão-Pêgo, Paloma; Dias, Suelen da Silva Gomes; Fintelman-Rodrigues, Natália; Temerozzo, Jairo Ramos; Carels, Nicolas; Alves, Carlos Roberto; Pereira, Mirian Claudia de Souza; Provance-Jr, David William; De-Simone, Thiago M

doi:10.1101/2021.04.16.440124

Cited by 16 publications

(1 citation statement)

References 70 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MX1 expression levels were reported to be significantly increased in COVID-19 patients ( 35 ). Notably, MX1 can be induced by hemin, a United States Food and Drug Administration approved drug, which exhibits inhibitory effects on SARS-CoV-2 replication ( 35 , 82 Preprint ). We also found FN1 levels to be similarly changed by both viruses and therefore representing a potential shared therapeutic target that not only plays a role in immune response and cell organization but also in kidney pathology.…”

Section: Discussionmentioning

confidence: 99%

Proteomic landscape of SARS-CoV-2– and MERS-CoV–infected primary human renal epithelial cells

et al. 2022

View full text Add to dashboard Cite

Acute kidney injury is associated with mortality in COVID-19 patients. However, host cell changes underlying infection of renal cells with SARS-CoV-2 remain unknown and prevent understanding of the molecular mechanisms that may contribute to renal pathology. Here, we carried out quantitative translatome and whole-cell proteomics analyses of primary renal proximal and distal tubular epithelial cells derived from human donors infected with SARS-CoV-2 or MERS-CoV to disseminate virus and cell type–specific changes over time. Our findings revealed shared pathways modified upon infection with both viruses, as well as SARS-CoV-2-specific host cell modulation driving key changes in innate immune activation and cellular protein quality control. Notably, MERS-CoV infection–induced specific changes in mitochondrial biology that were not observed in response to SARS-CoV-2 infection. Furthermore, we identified extensive modulation in pathways associated with kidney failure that changed in a virus- and cell type–specific manner. In summary, we provide an overview of the effects of SARS-CoV-2 or MERS-CoV infection on primary renal epithelial cells revealing key pathways that may be essential for viral replication.

show abstract

Section: Discussionmentioning

confidence: 99%

Proteomic landscape of SARS-CoV-2– and MERS-CoV–infected primary human renal epithelial cells

et al. 2022

View full text Add to dashboard Cite

show abstract

Coronavirus pathogenesis in mice explains the SARS-CoV-2 multi-organ spread by red blood cells hitch-hiking

Toro

Arevalo

Pereira-Gómez

et al. 2023

Preprint

View full text Add to dashboard Cite

SARS-CoV-2 infection causes a multisystemic disease that affects numerous organs beyond the respiratory system. Thus, it is well known that COVID-19 is associated with a wide range of hematological disorders; however, it remains unclear how the SARS-CoV-2 virus is able to navigate from tissue to tissue. In this work, we performed a comprehensive analysis of the pleiotropic effects of a prototypical coronavirus in its natural host, the validated preclinical model of murine hepatitis virus (MHV). Throughout this study we compared our results with the real-world data from COVID-19 patients (including autopsies). Thus, the presence of viral RNA was only detected in less than 25% of the human serum samples, whereas all had multiple positive nasal swabs for SARS-CoV-2. Notably, we found viral RNA not only in lungs, but also in heart and kidney of deceased COVID-19 patients. Subsequently, we investigated the association between viral organotropism and clinical manifestations employing the MHV murine model. Results from RT-qPCR and viral infectivity showcased the presence of viral RNA and infectious particles in multiple organs including liver, lung, brain, heart, kidney, spleen and pancreas, and even the blood of infected mice. Surprisingly, when comparing plasma and red blood cells (RBCs)-enriched fraction, higher viral load levels were detected in RBCs, with decreased RBC count, and hematocrit and hemoglobin levels in infected mice. Next, we treated infected mice with hemin triggering more aggressive symptoms. Strikingly, when combining hemin treatment with chloroquine (a compound that known to interact with the heme group and induces a conformational change in its structure) the infection and its clinical manifestations were distinctly attenuated. Computational docking suggested that heme is able to bind to MHV Spike protein in a similar way to the one, experimentally observed for SARS-CoV-2. Overall, our results lead to a global perspective of COVID-19 beyond the canonical focus on the respiratory system, and strongly support the multi-organ extent of coronavirus infection through specific interactions with RBC hemoproteins.

show abstract

A Journey into the Clinical Relevance of Heme Oxygenase 1 for Human Inflammatory Disease and Viral Clearance: Why Does It Matter on the COVID-19 Scene?

et al. 2022

View full text Add to dashboard Cite

Heme oxygenase 1 (HO-1), the rate-limiting enzyme in heme degradation, is involved in the maintenance of cellular homeostasis, exerting a cytoprotective role by its antioxidative and anti-inflammatory functions. HO-1 and its end products, biliverdin, carbon monoxide and free iron (Fe2+), confer cytoprotection against inflammatory and oxidative injury. Additionally, HO-1 exerts antiviral properties against a diverse range of viral infections by interfering with replication or activating the interferon (IFN) pathway. Severe cases of coronavirus disease 2019 (COVID-19), an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are characterized by systemic hyperinflammation, which, in some cases, leads to severe or fatal symptoms as a consequence of respiratory failure, lung and heart damage, kidney failure, and nervous system complications. This review summarizes the current research on the protective role of HO-1 in inflammatory diseases and against a wide range of viral infections, positioning HO-1 as an attractive target to ameliorate clinical manifestations during COVID-19.

show abstract

SARS-CoV-2 proteins bind heme and hemoglobin

Cited by 16 publications

References 70 publications

Proteomic landscape of SARS-CoV-2– and MERS-CoV–infected primary human renal epithelial cells

Proteomic landscape of SARS-CoV-2– and MERS-CoV–infected primary human renal epithelial cells

Coronavirus pathogenesis in mice explains the SARS-CoV-2 multi-organ spread by red blood cells hitch-hiking

A Journey into the Clinical Relevance of Heme Oxygenase 1 for Human Inflammatory Disease and Viral Clearance: Why Does It Matter on the COVID-19 Scene?

Contact Info

Product

Resources

About