August 8, 2022

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Metformin can be used to boost immunity of AIDS patients

Metformin exposes HIV weakness and can be used to boost immunity of AIDS patients



Metformin exposes HIV weakness and can be used to boost immunity of AIDS patients.

In the pharmaceutical industry, there is a special drug- Metformin (Metformin) . Metformin is the first-line drug for the treatment of type 2 diabetes and is used by hundreds of millions of patients worldwide.

Interestingly, recent studies have found that metformin in addition to lowering blood sugar , lose weight , but also improve lipid metabolism , reduce the risk of cardiovascular complications , and even anti-aging and anti-tumor effect. These many curative effects also make metformin regarded as the ” magic medicine “.


What surprises can metformin bring us?

March 2021, researchers at University of North Carolina School of Medicine in Nature sub-Journal Nature Immunology published a report entitled on: Multi-OMICS Analyzes the Reveal that HIV-1 alters the Cell CD4 + T Virus Replication of the Fuel immunometabolism to research papers.

The study found that metformin can act on mitochondrial respiratory chain complex I, inhibit the oxidative phosphorylation (OXPHOS) pathway, and thereby inhibit the replication of human CD4+ T cells and HIV-1 virus in humanized mouse models .

This finding suggests that metformin, like other drugs that reduce T cell metabolism, can be used as an adjuvant therapy for the treatment of AIDS.

Metformin exposes HIV weakness and can be used to boost immunity of AIDS patients

AIDS (AIDS)is a kind of a defective human immunodeficiency virus (HIV)caused great danger of infectious diseases.

HIV can attack the human immune system. AIDS patients are often infected with various diseases or tumors due to the collapse of the immune system. Therefore, the mortality rate of AIDS patients is extremely high.

Not only that, the high mutation rate and high drug resistance make AIDS an ” incurable disease .” Although the ” cocktail therapy ” invented by Dr. David Ho  can effectively control the HIV virus load in patients, as a combination therapy, “cocktail therapy” is often accompanied by severe side effects and requires the patient daily Taking medicine is expensive.

From this point of view, it is very important to find an effective and relatively cheap therapeutic drug for the treatment and prognosis of AIDS patients.

In this study, the research team noticed that patients infected with HIV-1 will show changes in the metabolism of CD4+ T cells .

Therefore, the researchers analyzed the transcriptome of CD4+ T cells from HIV-1 infected patients and revealed that elevated oxidative phosphorylation (OXPHOS) pathway is associated with poor prognosis.

Metformin exposes HIV weakness and can be used to boost immunity of AIDS patientsTranscriptome analysis of CD4+ T cells in HIV-1 infected patients

Specifically, in AIDS patients, HIV-1 load is positively correlated with the expression of mitochondrial innate immune receptor NLRX1 .

Not only that, quantitative proteomics and metabolic analysis revealed this mechanism: HIV-1 infection induces the binding of NLRX1 to the mitochondrial protein FASTKD5 and promotes the expression of mitochondrial respiratory complex, thereby enhancing the OXPHOS and glycolysis process, and ultimately promoting virus replication .

Metformin exposes HIV weakness and can be used to boost immunity of AIDS patients
The expression of NLRX1 is positively correlated with HIV-1 viremia and OXPHOS pathway

This study shows that the oxidative phosphorylation (OXPHOS) pathway in CD4+ T cells can be used as a target for HIV-1 therapy .

Therefore, the researchers further explored which drugs can inhibit the oxidative phosphorylation pathway.

It is worth noting that the FDA-approved cheap, safe and widely used hypoglycemic drug- metformin , can just inhibit the OXPHOS pathway.

Further experiments have also confirmed that drugs and other compounds that inhibit the oxidative phosphorylation of CD4+ T cells, such as metformin, can indeed inhibit the replication of HIV-1 in primary CD4+ T cells and humanized mouse models.

Metformin exposes HIV weakness and can be used to boost immunity of AIDS patientsMetformin can inhibit HIV-1 replication in primary CD4+ T cells and humanized mice

In addition, the research team’s statistical analysis based on an HIV-1 patient treatment study showed that diabetes-AIDS patients who took antiretroviral drugs and metformin at the same time had a better prognosis .

Specifically, these patients have higher levels of CD4+ T cells, and the average level of HIV in the blood is 33% lower than that of AIDS patients who do not take metformin!

In response, Jenny Ting , the corresponding author of this study, said: “This work shows the importance of CD4+ T cell metabolism in HIV-1 replication, and suggests that it may be targetable.

For example, it can be safe through metformin and others. And cheap metabolic drugs to reduce the viral load of HIV-1 and restore the level of CD4+ T cells in the patient’s body .”

Schematic diagram of this study

All in all, this study shows that HIV-1 infection can lead to changes in the metabolism of CD4+ T cells, and the increase in the oxidative phosphorylation pathway is related to the poor prognosis of patients .

More importantly, the study also revealed that drugs that inhibit the oxidative phosphorylation pathway, such as metformin , may be adjuvant therapies for the treatment of AIDS, and guide new AIDS combination medication programs in the future.

references:
https://www.nature.com/articles/s41590-021-00898-1
https://www.nature.com/articles/s41590-021-00881-w

Metformin exposes HIV weakness and can be used to boost immunity of AIDS patients.

(source:internet, reference only)


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