Bevirimat
Encyclopedia
Bevirimat is an anti-HIV drug derived from a betulinic acid
-like compound, first isolated from Syzygium
claviflorum, a Chinese herb. It is believed to inhibit HIV
by a novel mechanism, so-called maturation inhibition. It is not currently U.S. Food and Drug Administration (FDA) approved, but is undergoing clinical trials conducted by the pharmaceutical company Panacos
. Myriad Genetics
announced on January 21, 2009 the acquisition of all rights to Bevirimat for $7M USD.
ranged from 173.9 to 185.8 mL/hour."
, bevirimat and other maturation inhibitors interfere with protease processing of newly translated HIV polyprotein precursor, called gag. This molecule contains a number of HIV proteins in a single polypeptide which is then cleaved by the enzyme protease to produce functional structural proteins. However, unlike the protease inhibitors, bevirimat binds the gag protein, not protease. Once bound to gag, bevirimat prevents a critical cleavage at a site called the capsid-SP1 junction. The resulting virus particles lack functional capsid protein and have structural defects, rendering them incapable of infecting other cells. For reasons not entirely understood, protease inhibitor
-resistant HIV-1 was hypersensitive to bevirimat in vitro
. In 2010 a study about bevirimat resistance prediction based on HIV-1 genotype has been published.
Betulinic acid
Betulinic acid is a naturally occurring pentacyclic triterpenoid which has anti-retroviral, anti-malarial, and anti-inflammatory properties, as well as a more recently discovered potential as an anticancer agent, by inhibition of topoisomerase...
-like compound, first isolated from Syzygium
Syzygium
Syzygium is a genus of flowering plants that belongs to the myrtle family, Myrtaceae. The genus comprises about 1100 species, and has a native range that extends from Africa and Madagascar through southern Asia east through the Pacific...
claviflorum, a Chinese herb. It is believed to inhibit HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
by a novel mechanism, so-called maturation inhibition. It is not currently U.S. Food and Drug Administration (FDA) approved, but is undergoing clinical trials conducted by the pharmaceutical company Panacos
Panacos Pharmaceuticals
Panacos Pharmaceuticals is a Delaware based pharmaceutical corporation founded in 1999. Panacos is engaged in the discovery and development of inventive therapeutics and technologies to help fight major viral illnesses. As of now, their focus is on Human Immunodeficiency Virus anti-infectives,...
. Myriad Genetics
Myriad Genetics
Myriad Genetics, Inc. is a molecular diagnostic company based in Salt Lake City, Utah. Myriad employs a number of proprietary technologies that permit doctors and patients to understand the genetic basis of human disease and the role that genes play in the onset, progression and treatment of disease...
announced on January 21, 2009 the acquisition of all rights to Bevirimat for $7M USD.
Clinical trials
In December 2007, some results of the Phase IIb trial were released. Thomson Financial News reported that, "some patients respond 'very well' to the drug, while another population 'does not respond as well at current dose levels.'" Panacos said it intends to add a group to the study at a higher dosage. The drug manufacturer, Panacos, has stated that success with Bevirimat hinges on a patient's particular HIV not having a specific group of genetic mutations in HIV’s Gag protein. When they evaluated the study participants’ virus and found that the participant’s virologic response depended greatly on whether or not the Gag protein of a participant’s virus had polymorphisms—multiple mutations in the protein’s structure. After sampling the virus of 100 patients in the company’s database, they found that about 50 percent did not have Gag polymorphisms, meaning that about 50 percent would likely respond well to the drug.Pharmacokinetics
According to the only currently available study, "the mean terminal elimination half-life of bevirimat ranged from 56.3 to 69.5 hours, and the mean clearanceClearance (medicine)
In medicine, the clearance is a measurement of the renal excretion ability. Although clearance may also involve other organs than the kidney, it is almost synonymous with renal clearance or renal plasma clearance. Each substance has a specific clearance that depends on its filtration characteristics...
ranged from 173.9 to 185.8 mL/hour."
Mechanism of action
Like protease inhibitorsProtease inhibitor (pharmacology)
Protease inhibitors are a class of drugs used to treat or prevent infection by viruses, including HIV and Hepatitis C. PIs prevent viral replication by inhibiting the activity of proteases, e.g.HIV-1 protease, enzymes used by the viruses to cleave nascent proteins for final assembly of new...
, bevirimat and other maturation inhibitors interfere with protease processing of newly translated HIV polyprotein precursor, called gag. This molecule contains a number of HIV proteins in a single polypeptide which is then cleaved by the enzyme protease to produce functional structural proteins. However, unlike the protease inhibitors, bevirimat binds the gag protein, not protease. Once bound to gag, bevirimat prevents a critical cleavage at a site called the capsid-SP1 junction. The resulting virus particles lack functional capsid protein and have structural defects, rendering them incapable of infecting other cells. For reasons not entirely understood, protease inhibitor
Protease inhibitor (pharmacology)
Protease inhibitors are a class of drugs used to treat or prevent infection by viruses, including HIV and Hepatitis C. PIs prevent viral replication by inhibiting the activity of proteases, e.g.HIV-1 protease, enzymes used by the viruses to cleave nascent proteins for final assembly of new...
-resistant HIV-1 was hypersensitive to bevirimat in vitro
In vitro
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...
. In 2010 a study about bevirimat resistance prediction based on HIV-1 genotype has been published.