A potential bimodal interplay between heme and complement factor H 402H in the deregulation of the complement alternative pathway by SARS-CoV-2.

The recent discovery that the trimeric SARS-CoV-2 spike S glycoprotein carries heme within an NTD domain pocket of the S1 subunits, suggested that this virus may be cleverly utilizing heme, in addition to the S1 RBD domains, for invading target cells carrying a specific entry receptor like ACE2, TMEM106B and others. Studies during the COVID-19 pandemic revealed that the infectivity of this virus depends on cell surface heparan sulfate and that the infection induces non-canonical activation of the Complement Alternative pathway (AP) on the surface of infected cells. In our recent COVID-19 genomic studies, among the coding SNPs of interest we also detected the presence of the CFH rs1061170, rs800292 and rs1065489 within all the infected patient subgroups examined.

Targeting mitochondrial bioenergetics by combination treatment with imatinib and dichloroacetate in human erythroleukemic K‑562 and colorectal HCT‑116 cancer cells.

Tumor malignant cells are characterized by dysregulation of mitochondrial bioenergetics due to the 'Warburg effect'. In the present study, this metabolic imbalance was explored as a potential target for novel cancer chemotherapy. Imatinib (IM) downregulates the expression levels of and () genes involved in the heme‑dependent cytochrome oxidase biosynthesis and assembly pathway in human erythroleukemic IM‑sensitive K‑562 chronic myeloid leukemia cells (K‑562).

Heme Interactions as Regulators of the Alternative Pathway Complement Responses and Implications for Heme-Associated Pathologies.

Heme (Fe-protoporphyrin IX) is a pigment of life, and as a prosthetic group in several hemoproteins, it contributes to diverse critical cellular processes. While its intracellular levels are tightly regulated by networks of heme-binding proteins (HeBPs), labile heme can be hazardous through oxidative processes. In blood plasma, heme is scavenged by hemopexin (HPX), albumin and several other proteins, while it also interacts directly with complement components C1q, C3 and factor I.

Targeted genotyping of COVID-19 patients reveals a signature of complement C3 and factor B coding SNPs associated with severe infection.

We have attempted to explore further the involvement of complement components in the host COVID-19 (Coronavirus disease-19) immune responses by targeted genotyping of COVID-19 adult patients and analysis for missense coding Single Nucleotide Polymorphisms (coding SNPs) of genes encoding Alternative pathway (AP) components. We have identified a small group of common coding SNPs in Survivors and Deceased individuals, present in either relatively similar frequencies (CFH and CFI SNPs) or with stark differences in their relative abundance (C3 and CFB SNPs). In addition, we have identified several sporadic, potentially protective, coding SNPs of C3, CFB, CFD, CFH, CFHR1 and CFI in Survivors.

Targeted Genotyping of MIS-C Patients Reveals a Potential Alternative Pathway Mediated Complement Dysregulation during COVID-19 Infection.

Complement dysregulation has been documented in adults with COVID-19 and implicated in relevant pediatric inflammatory responses against SARS-CoV-2. We propose that signatures of complement missense coding SNPs associated with dysregulation could also be identified in children with multisystem inflammatory syndrome (MIS-C). We investigated 71 pediatric patients with RT-PCR validated SARS-CoV-2 hospitalized in pediatric COVID-19 care units (November 2020-March 2021) in three major groups.