Image Source: thestar.com
Image Source: thestar.com

[box type=”default” size=”large”] It attacks proteins that allow replication of viruses [/box]

Researchers at the Virginia Commonwealth University (VCU) in the US have attested to the effectivity of Viagra and other drugs that offset erectile dysfunction in attacking a protein that abets the replication of cancer cells and viruses.

The team, led by Dr. Paul Dent, reported its findings in last month’s issue of the Journal of Cellular Physiology.

Dent said his team found out that a protein called GRP78 could be a universal therapeutic target for treating human diseases like brain cancer, ebola, Influenza, Hepatitis and superbug bacteria such as MRSE and MRSA.

Their study showed that a drug combination of the clinically tested OSU-03012 (AR-12) and FDA approved Phosphodiesterase 5 Inhibitors (Viagra, Cialis) that targets GRP78 and related proteins prevented the replication of a variety of major viruses in infected cells and made antibiotic-resistant bacteria vulnerable to common antibiotics.

Moreover, they found evidence that brain cancer stem cells were likewise eliminated.

Data were obtained from multiple brain cancer stem cell types and viruses that cause influenza, mumps, measles, rubella, RSV and CMV, as well as adenovirus, Coxsakie virus, Chikungunya, Ebola, Hepatitis, E. coli, MRSA, MRSE and N. Gonorrhoeae.

“Basically, we’ve got a concept that by attacking GRP78 and related proteins: (a) we hurt cancer cells; (b) we inhibit the ability of viruses to infect and to reproduce; and (c) we are able to kill superbug antibiotic-resistant bacteria,” said Dent, a professor at the Department of Biochemistry and Molecular Biology at the VCU School of Medicine.

He is also VCU’s universal chairman for signal trnasduction.

Dent said GRP78 is part of a family of proteins called chaperones, whose job is to help shape chains of amino acids into proteins and keep those proteins active in the correct 3D shape.

He added that the OSU/Viagra drug combination attacks GRP78 and other chaperones, thereby killing cancer cells.

Upon learning of the drug combination’s effect on GRP78 in cancer cells, Dent and his team started targeting GRP78 for infectious diseases such as viruses and bacteria.

He said chaperone proteins are very important in cancer cells or virus-infected cells as these cells make extra protein compared to normal and uninfected cells.

The team, Dent added, found that the OSU/Viagra drug combination reduced infectivity through reduced viral receptor expression on the surface of target cells and the prevention of virus replication in infected cells.

He said the drug combination was able to reduce the expression of viral receptors for ebola, marburg, hepatitis A, B and C, and lassa fever viruses.

Among cancer cells, the drug combination also reduced the expression of oncogene receptors.

Dent said among bacteria, the drug combination reduced the expression of the equivalent GRP78 protein called Dna K, and induced cell death in pan-antibiotic resistant forms of E. coli, MRSE, MRSA and N. gonorrhoeae.

“The findings open an avenue of being able to treat viral infections, infections that certainly most people would say we’ll never be able to treat; they prove that GRP78 is a ‘drugable’ target to stop viruses from reproducing and spreading,” Dent said.

“In the case of bacteria, we have a new antibiotic target, Dna K, that if we’re careful and only use the OSU drug in hospitals, we’ve got something that can help to treat the superbugs,” he added.

Dent said that the next steps have already been taken and are leading to new discoveries: “We know that the OSU/Viagra treatment can kill tumor cells among mice but doesn’t harm normal tissues like the liver and the heart. Of even more importance we’ve just discovered that the OSU/Viagra combination can reduce the levels of proteins called ‘pumps’ in the mouse brain. Pumps are responsible for making tumor cells resistant to chemotherapy and for stopping life-saving brain cancer chemotherapy from entering into the brain and killing cancer.”

VCU researchers previously are not strangers to the benefits of the Viagra drug combinations.

Back in 2010, Dr. Rakesh Kukreja, scientific director of the VCU Pauley Heart Center and the Eric Lipman professor in cardiology in the VCU School of Medicine, collaborated with Dent and found that Viagra improved the effectiveness of the breast cancer treatment Doxorubicin while protecting the heart from harm caused by the chemotherapy.

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