Drug that targets drug-resistant strains of HIV and other viruses is ready for clinical trials

 

The relatively new (mid 2000s) protein OSU-03012, also known as AR-12 is ready to begin clinical testing against drug-resistant strains of HIV and other viruses.

Recently, AR-12 has also become one of the principle drugs tested against the Ebola virus. The two-year-long epidemic that infected 28,000 people and killed more than 11,000 in Liberia, Guinea and Sierra Leone.

“Basically, we have fully worked out how the drug works and why it stops so many different kinds of ,” said lead researcher Paul Dent, Ph.D., professor in the Department of Biochemistry and Molecular Biology at Virginia Commonwealth University School of Medicine and Universal Chair for Signal Transduction.

In an animal model of hemorrhagic fever virus, a transient exposure of animals to low doses of AR-12 doubled animal survival from ∼30% to ∼60% and suppressed liver damage. Thus through inhibition of chaperone protein functions; reducing the production, stability and processing of viral proteins.

The “chaperone” in reference is a protein called GRP78. The job of a chaperone protein is to keep enzymes and virus coat proteins in their correct three-dimensional shape. If an enzyme or coat protein has an incorrect 3-D shape, the enzyme does not work and the coat protein cannot form into a new virus cell.

Over the past 25 years, GRP78 has been found to be essential for the replication of almost every type of pathogenic virus. Chaperone proteins are very important in cancer cells or virus infected cells because these cells make extra proteins that dictate what these cells will be.

“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. “And 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.”

AR-12 targets these cells directly, rewiring how they work and causing them to inevitably die before they spread. According to  the same team at Virginia Commonwealth University, an  OSU-03012/Viagra drug combination reduced infectivity of viruses on the surface level, and prevented virus replication in infected cells.

The drug combination was able to reduce expression of viral receptors for Ebola, Marburg, Hepatitis A, B and C, and Lassa fever viruses. In cancer cells the drug combination reduced the expression of oncogene receptors, too.

These findings are found in a controlled setting, with controlled tests, but the results are nonetheless promising in the fight against increasingly elusive virus’.

 

Sources:

http://www.scbt.com/datasheet-364560-CASNumber-742112-33-.html

http://medicalxpress.com/news/2014-12-protein-grp78-universal-therapeutic-multiple.html

http://www.ncbi.nlm.nih.gov/pubmed/27187154

https://news.vcu.edu/article/The_protein_GRP78_identified_as_possible_universal_therapeutic

http://www.nbcnews.com/storyline/ebola-virus-outbreak/ebola-study-test-new-drug-men-whose-semen-harbors-virus-n603866

http://www.arnothera.com/pr150514.html

http://medicalxpress.com/news/2016-07-drug-multiple-drug-resistant-strains-hiv.html

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