It is not a surprise anymore that the pandemic we are facing with now, is not only about respiratory system. We saw COVID-19 long haulers suffer neuroinvasion symptomps. There are also people that are still having tinnitus months after the virus aren't detected anymore. In children we read about MIS-C (Multi-system Inflammation Syndrome in Children).
Noncancer medications example that used in COVID-19 is metformin. Medication with metformin (type 2 Diabetic drug) in COVID-19 patients resulted in modest decrease of viral loads. Metformin is known to inhibit Complex I in mitochondrial metabolism. This suggests that SARS-CoV-2 hijacks Complex I in order to replicate in the cell.
My previous article suggested to use certain anticancer drugs to inhibit the main protease of SARS-CoV-2. Cancer cells prefer glycolysis instead of oxidative phosphorylation. It is interesting to look at the proteins involved in it. The late Susan Lindquist from MIT in one of her lectures mentioned that we could not separate our life from the proteins. Proteins are the core of living organisms. Researchers at the University of California proposed oncogenic pathways identifying protein-protein interaction of human and SARS-CoV-2.
They mapped a network of virus-host protein-protein interactions by purification of 26 of the 29 SARS-CoV-2 proteins. They found 332 (46 proteins that are either known or candidate cancer genes) proteins that are targeted by SARS-CoV-2. They also identified 69 FDA approved drugs or compounds in clinical trials and preclinical development that could be repurposed fro inhibition of indentified virus-host protein-protein interactions.
The researchers identified a variety of proteins with roles related to cell-cell progression, especially proteins associated with the centrosome, mitotic spindle, regulation of cytokinesis. Centrosomes are structures that are found within the cytoplasm of cells and are involved in cell division. Mitotic spindle has a crucial role in ensuring the accurate segregation of chromosomes into the two daughter cells during cell division, which is paramount for maintaining genome integrity. Cytokinesis is the process by which one cell physically divides into two cells.
SARS-CoV-2 Proteins that Interact with Cancer Genes
Nsp 7 from SARS-CoV-2 has a job in replication of the viral genome, an essential cofactor of the RNA-dependant RNA polymerase. Nsp 9 binds single-stranded RNA. Nsp 13 is a helicase/triphosphatase. Among them, there are 12 centrosome-associated proteins, protein-A-kinase (PKA) signaling components as well as proteins with roles in the regulation of mitotic progression and cytokinesis.
N, E, Orf, and Nsp proteins interactions with cancer genes:
- N protein interacts with 4 genes (stress granule regulation) and 9 genes (translation/RNA processing),
- E protein interacts with 2 genes (epigenetic/chromatin),
- Orf 3a interacts with 1 gene (metabolism),
- Orf 6 interacts with 2 genes (translation/RNA processing),
- Orf 8 interacts with 3 genes (metabolism), 1 gene (epigenetic/chromatin), and 1 gene,
- Orf 9b interacts with 3 genes (protein complex/biological process) and 2 genes,
- Orf 9c interacts with 4 proteins (metabolism),
- Orf 10 interacts with 5 genes (protein complex/ biological process),
- Nsp 1 interacts with 4 genes (cell cycle/DNA damage),
- Nsp 2 interacts with 2 genes (protein complex/ biological process) and 1 gene,
- Nsp 5 interacts with 1 gene (epigenetic/chromatin),
- Nsp 7 interacts with 4 genes (metabolism) and 3 genes (protein complex/ biological process)
- Nsp 8 interacts with 1 gene (translation/RNA processing), 1 gene (epigenetic/chromatin), 1 gene,
- Nsp 9 interacts with 8 genes (protein complex/ biological process), 1 gene (cell cycle/DNA damage), and 1 gene,
- Nsp 12 interacts with 1 gene (cell cycle/DNA damage), 1 gene (translation/RNA processing), 5 genes,
- Nsp 13 interacts with 3+12 genes (cell cycle/DNA damage), 2+3+6 genes (protein complex/ biological process), 3 genes,
- Nsp 14 interacts with 2 genes (metabolism).
SARS-CoV-2 might be perturb the fundamental process in mitochondrial metabolism and oxidative stress. The researchers reported some proteins with role in lipid metabolism, glycosylation, and amino acid metabolism that were involved during the SARS-CoV-2 infection.
Epigenetics changes induced by histone methyl-transferase and deacetylases were shown to be important for viral infection and cancer progression, e.g. shown in Eipstein-Barr virus associated with cancer. In SARS-CoV-2, Orf 8 interacts with DNA methyl-transferase, Nsp 8 interacts with histone methyl-transferase NSD2 (gene).
Nsp 1 is known to associate with 40S ribosomes and selectively induce endonucleolytic cleavage of host mRNAs. N protein binds to mRNA 5' cap structure and be involved in mRNA stabilization, intercts with LARP1. LARP1 (gene) which is upregulated in cancers especially associated with viral infections and was shown to promote tumorigenesis.
Source:
https://pubmed.ncbi.nlm.nih.gov/32444466/
Picture taken from:
https://pubmed.ncbi.nlm.nih.gov/32444466/