Cell Rep Breaks! New drugs wake up sleep of HIV virus, can functionally cure HIV!

, June 28, 2020 /PRNewswire/
BioValley scientists at the Sanford Burnham Prebi Institute for Medical Discovery have developed a new generation of drug, Ciapavir (SBI-0953294), which effectively activates the dormant human immunodeficiency virus (HIV)The study, published in Cell Reports Medicine, aims to create an effective cure for AIDS -- known as "shock and kill" -- by activating and eliminating all latent HIVscientists have found that other "shock" methods are either too hot to over-activate the immune system or too cold to activate the immune system to kill the virusSumit Chanda, director of the Immune and Pathogensprograms Program at the Institute of Medical Discovery and co-author of the study, saidOur study found a more effective drug -- it wakes up the virus without activating the immune systemOur work also provides further evidence that the drug, known as the Smac simulation, is a promising way to reactivate the latent HIV virus"
picture from: Seth Pincus, Elizabeth Fischer and Austin Athman, National Institutes of Allergy and The Diseases, National Institutes of HealthAnti-Retroviral Therapy (ART) has extended life expectancy for people living with HIV by decades, many of whom already live as long as the general populationHowever, because HIV can be hidden in the body's host cells, the infected person can never completely remove the disease, so the person must take antiretroviral drugs daily for the rest of the life to make the virus inactiveAs with other chronic therapies, ART's non-compliance rate is estimated at 30%Non-adherence to treatment increases the likelihood of HIV developing into AIDS (late-stage infection) and increases the risk of treating drug resistancewake up sleeping HIVthe study builds on a previously discovered Smac simulator by scientists that has been tested for human safety and is currently undergoingclinical trials for certain cancers it reactivates latent viruses in cells of AIDS patients undergoing antiretroviral therapy At the same time, scientists are exploring ways to kill reactivated viruses -- such as developing extensive neutralizing antibodies or destroying modified T-cells (CAR-T cell therapy) that infect infected cells -- that would complete the "shock and kill" strategy in the study, researchers gave Ciapavir to mice with human immune systems and HIV infection This treatment significantly increases levels of HIV in the blood and bone marrow -- indicating that the latent virus is activated Importantly, immune activation is minimal Overactivation of the immune system can be fatal and has historically been a problem with "shock and kill" methods "Ciapavir is the first Smac simulation specifically designed to cure AIDS, so it's obviously more effective than these molecules," said Dr Nicholas Cosford, deputy director of the NCI-designated Cancer Center in Sanford Burnham And co-author of the study "Thus, Ciapavir alone may be effective without combining with another drug, as we have previously demonstrated, and may be a low dose," said Mr Ciapavir a gentle approach Ciapavir is a small molecule that wakes up dormant HIV by activating the unconventional NF-B signal in CD4 plus T cells, and CD4-T cells are the target of HIV This less-used approach activates only a subset of the immune system, which is key to the drug's gentle approach "Unconventional NF-B signals are part of the immune system's response to pathogens," said Lars Pache, ," said Lars Pache, the study'
lead author of cell Reports and an assistant professor at Chanda Labs In this case, we use this alternative to achieve our advantage We can wake up the virus without destroying the immune system "
researchers will next conduct further assessments in non-human primates, as well as additional toxicology studies to ensure that the drug can be tested in humans." Dr Rowena Johnston, vice president and research director of the AIDS Research Foundation, said: "The early attempts to cure AIDS and the kill method used re-used drugs, but did not achieve the goal of reactivating the latent HIV to a useful level It is encouraging to see the field of HIV treatment moving towards targeted treatments to achieve the goals that have so far been difficult to achieve More than 37.9 million people worldwide are living with HIV, including 1.1 million in the United States, according to the World Health Organization HIV-infected body immune system CD4 plus T cells As the infection progresses, the immune system is destroyed, making people more vulnerable to other infections and diseases In the absence of drugs, AIDS patients or people with advanced AIDS usually survive for about three years (BioValleyBioon.com) References: New Drug Candidate reawakens Sleeping HIV in hopes of the scientists reawaken sleeping HIV in patient patient to the cancer the virus
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Sumit Chandaet al.
The ixical Activation of Non-canonical NF-B Signaling Activates Late-1 Reservoirs In Vivo Cell Reports Medicine, DOI: 10.1016/j.xcrm.2020.100037
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