Science and Technology

Medicine against AIDS can be effective against the herpes virus

Results of the study is the first step to developing a drug for the entire family of Herpesviridae

Foto: Divulgação/IRB Barcelona
Structure of UL89 protein, which could be a valid target against all Herpesviridae (c) Laboratory Miquel Coll.
Structure of UL89 protein, which could be a valid target against all Herpesviridae (c) Laboratory Miquel Coll.

Scientists from the Institute for Research in Biomedicine (IRB Barcelona), Spain, led by researcher Miquel Coll, published a new study showing that the Raltegravir, the drug approved in 2007 for the treatment of AIDS, nullifies the function of UL89 protein, essential for the replication of a type of herpes virus. The study is the first step to developing a drug against all of the herpes virus family.

"These results have a medical impact evident for three reasons. First, humans do not have a viral protein that is affected, which would allow a highly specific drug that has shown no side effects that other drugs can have. Secondly, the inhibitor does not is toxic to humans when administered at therapeutic concentrations, because it is already on the market and thus the toxicity tests are facilitated, and third, we have data indicating that all herpes viruses have this protein. Thus, it could be a valid target against all Herpesviridae, "explains Miquel Coll said.

The herpes viruses include pathogens such as herpes simplex 1 and 2, the virus that causes chickenpox also known as herpes zoster virus, Epstein-Barr virus, associated with various types of cancer, the roseola virus, cytomegalovirus and viruses herpes associated with Kaposi's sarcoma in AIDS patients.

Human cytomegalovirus (HCMV), in which the study was conducted, causes neurological defects in 1% of newborns in developed countries. It also causes retinitis deteriorates to blindness in 25% of individuals with AIDS, defects in the brain and central nervous system of young adults, inflammation of the colon, also in those with AIDS, mononucleosis and severe diseases of the throat. Although 90% of adults carry HCMV, the virus is opportunistic, acting in people with weakened immune systems, such as patients with cancer, AIDS, patients who received an organ transplant and newborns.

To replicate, the herpes virus enters the nucleus of a cell where he uses the cellular machinery to copy their DNA many times in a single large string. Since this copy was made, it acts as a complex called terminase, composed of three subunits of the protein. The terminase cuts the new DNA into small fragments, the size of a single viral genome, and presents them in empty shells (capsids) that developed in the cell nucleus. Then, the new viruses leave the cell to continue the infection. The researchers identified the 3D structure of part of the terminase and when they observed that resembled the integrase of the AIDS virus, for which drugs are available, they tested the protein against the herpes virus. Thus, they found that Raltegravir works in the UL89 subunit of terminase and nullifies the function of "scissors", which is necessary for viral replication. The tests were carried out directly on proteins in test tubes.

"Now we have to do the testing set of infected cells, improve and validate drug effect that is also effective for other types of herpes virus," explains Miquel Coll.