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Heart Drug Blocks the Reactivation of HIVĀ 

Heart Drug Blocks the Reactivation of HIVĀ 

Heart Failure Drug Apparently Blocks HIV-1 Reactivation

A drug used to treat heart failure apparently blocks HIV-1 reactivation.

Medical progress in the world of HIV is nagged by the virus’ ability to become dormant, hide and rebound. A cure, however, is no longer considered a distant pipe dream.

A recent study, ā€œScreening of an FDA-Approved Compound Library Identifies Levosimendan as A Novel anti-HIV-1 Agent that Inhibits Viral Transcription,ā€ published in Volume 146 of Antiviral Research identifies a drug typically used on people suffering from heart failure as harnessing previously unknown anti-HIV effects.

This work was performed by Tsuyoshi Hayashi, Maxime Jean, Huachao Huang, Sydney Simpson, Netty G Santoso, and Jian Zhu from the University of Rochester Medical Center. A few of the researchers involved in the study explained their methods of observation to Science Trends.

978 FDA-approved compounds were screened for their ability to block HIV-1 reactivation and one drug — levosimendan — stood out among the rest.

Fairly recent efforts to permanently suppress HIV includes the popular ā€œblock and lockā€ strategy in an attempt to reach stubborn HIV cells hidden in reservoirs in the body. Latency-promoting agents (LPA) are key to the block and lock strategy. LPAs have been added to cART regimens, although in a limited number, and the long term effects need further study.

The purpose of the study was tco find other potential LPAs among the vast plethora of already-known drugs. Levosimendan is a ā€œcalcium-sensitizing positive inotropic drugā€ and was one of the drugs selected for further study on potential effects that may be useful for the treatment of HIV-1.

ā€œTo identify novel HIV-1 LPA candidates,ā€ Tsuyoshi Hayashi and Jian Zhu wrote, ā€œwe screened an FDA-approved compound library, composed of 978 unique small-molecule compounds using HIV-1 latently infected cell line. A novel and promising anti-HIV-1 transcription inhibitor, levosimendan, was identified from these screens. Levosimendan is a calcium-sensitizing positive inotropic drug and currently used to treat acutely decompensated heart failure in clinics.ā€

Levosimendan is typically used for a completely different reason than for controlling HIV — it’s used to treat acute heart failure.

At times, drugs have multiple applications: one drug, many uses. That’s why nearly 1,000 already-approved drugs were combed through for potential bonus applications that could be applied in the world of HIV.

ā€œA new and promising anti-HIV-1 inhibitor, levosimendan,ā€ researchers wrote in the abstract, ā€œwas identified from these screens. Levosimendan is currently used to treat heart failure in clinics, but it demonstrates strong inhibition of TNFα-induced HIV-1 reactivation in multiple cell lines of HIV-1 latency through affecting the HIV-1 Tat-LTR transcriptional axis. Furthermore, we confirmed that in primary CD4+ T cells levosimendan inhibits both the acute HIV-1 replication and the reactivation of latent HIV-1 proviruses.ā€

HIV-1 targets and activates CD4+ T cells, causing a virus-induced cytopathic effect and cell apoptosis (programmed cell death). Some, however, survive and revert back to a resting state, forming the HIV-1 latent reservoirs. These cells harbor ā€œtranscriptionally silentā€ HIV-1 proviruses, which retain the ability to produce infectious HIV-1 virions.

The researchers added that levosimendan could be used specifically for its unique abilities to blockĀ  HIV-1 reactivation. ā€œ. . . Our studies successfully identify levosimendan as a novel and promising anti-HIV-1 inhibitor, which should be immediately investigated in vivo given that it is already an FDA-approved drug.ā€

The findings present a whole new library of potential applications for a drug that was originally intended for a completely different application.

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