Immunodeficiency virus 1 HIV

Human immunodeficiency virus-1 (HiV-1) For the treatment of HIV-1 infection in combination with appropriate antiretroviral agents when therapy is warranted. 

A recent example is the substrate analogue thymidine 5 -[a,P-imido]triphosphate [141171-20-2] (TMPNPP) (2) which competitively inhibits the human immunodeficiency virus-1 (HIV-1) reverse transcriptase (HIV-1 RT) with a K value of 2.4 micromolar ( TM) (9). The substrate is thymidine 5 -triphosphate... 

Because of the importance of l,3-diazepin-2-ones as human immunodeficiency virus 1 (HIV-1) protease inhibitors, considerable computational effort has been devoted to the analysis of the structure <1998JA4570> and binding properties <2004JME6673, 2004BMC5819, 1999JME249> of these compounds. 

In a more recent continuation of these studies, Campiani and co-workers carried out semi-empirical calculations on a series of active compounds related to 2. This led to the identification of several structural and conformational features responsible for this activity <2005JME4367>. Docking into the human immunodeficiency virus 1 (HIV-1) reverse transcriptase non-nucleotide binding site (RT NNBS) of a compound of type 3 (X = O) highlighted that one of the phenyl rings of this compound protrudes toward the catalytic site <2005JME7153>. 

The activity of triazepines 220 and 221 against the human immunodeficiency virus 1 (HIV-1) multiplication in acutely infected cells has been studied on the basis of inhibition of virus-induced cytopathogenicity in MT-4 cells. The triazepines 221 having a pyridine ring were found to be less potent than 220. The results of activity studies are given in Table 6. Nevirapine has been used as the reference <2000JHC1539>. 

Human immunodeficiency virus-1 (HIV-1) protease is an enzyme that breaks inactive polyproteins into their functional parts that are vital for the proper operation of HIV-1. This enzyme is a target for treatment of patients infected with HIV-1. HIV-1 protease operates as a dimeric complex, a trait that lends the enzyme to be inhibited by a drug that is highly symmetrical.24... 

Infection with human immunodeficiency virus-1 (HIV-1) can destroy the immune system and lead to AIDS the virus can induce severe and debilitating neurological problems as well (Ellis et al., 1997 Kaul et al., 2001, 2005 ... 

The constrained nucleosides are of interest as leads for small-molecule therapeutics. For example, the (3-2 -0,3 -C-oxetane analogues of the antiviral 3 -azido-3 -deoxythymidine (AZT), which exist predominantly in the E-like conformation (see, for example, Equation 55), were investigated for inhibition of human immunodeficiency virus 1 (HIV-1). Neither the modified nucleosides nor their 5 -monophosphate analogues inhibit HIV-1, supporting a hypothesis that reverse transcriptase inhibitors must have conformational freedom <2001JOC4878, 2002J(P1)1655>. 

Recently, it has been shown that oxidant stress can induce the expression and replication of human immunodeficiency virus-1 (HIV-1) in a human T cell line [64], The effect was shown to be mediated by the transcription factor NFk,B, which was potently and rapidly activated by exposure of target cells to H2O2. Moreover, the activation of NFkB by a variety of stimuli including phorbol-12-myristate-13-acetate (PMA), calcium ionophores and tumour necrosis factor alpha (TNFa) was inhibited by the ROI scavenger, N-acetyl cysteine [64]. It was therefore suggested that the formation of ROI was the common mechanism involved in the activation of NFk,B by a variety of agents. 

HISK, histidine-specific protein kinase HIS-R, histamine receptor HIV-1, human immunodeficiency virus 1 HIV-1 IN, HIV-1 integrase HIV-1 PR, HIV-1 protease HIV-1 RT, HIV-1 reverse transcriptase HMG protein, high mobility group protein... 

The BBB controls the exchange of nutrients, xenobiotics, and drugs between the brain and the systemic circulation. The BBB is a significant obstacle to achieving optimal concentrations of desirable therapeutics in the central nervous system, including agents for the treatment of stroke, cancer, Alzheimer s disease, and human immunodeficiency virus-1 (HIV-1) infection.22... 

Ritonavir (Norvir Abbott) is a drug for treating patients infected with human immunodeficiency virus-1 (HIV-1). In solid state the compound consists exclusively of one kind of monoclinic crystals. As this form, now called form I, was not sufficiently bioavailable by the oral route, a liquid formulation containing dissolved ritonavir in a hydroalcoholic solution was developed. It gave satisfactory results during the development and early manufacturing phases. However, in 1998, 2 years after the launch, a second form (form II) precipitated during shelf life. The new form is thermodynamically more stable and about 50% less water-soluble than form I. Within weeks-days, this new form was produced in all the production lines and Abbott had to stop the production of ritonavir. Finally, after considerable effort and expense, a new formulation of ritonavir was developed. 

Three pivotal papers that appeared in 1987 established the potency of castanospermine in inhibiting the replication of human immunodeficiency virus-1 (HIV-1) (254-256), and the intense activity that succeeded these revelations was documented in the previous review (2). Castanospermine is recognized as being one of the most powerful inhibitors of HIV-induced syncytium formation (virus-induced cell fusion), a crucial feature in the cell-to-cell transmission of HIV infection (257). It subsequently transpired that esters of (+ )-239 were even more effective inhibitors of HIV replication, no doubt because their lipophilic nature facilitates penetration through cell membranes, after which they are probably hydrolyzed to the parent alkaloid (216). Much of the current activity centers on 6-... 

The virus responsible for almost all the AIDS cases in the United States was identified by scientists at the Louis Pasteur Institute in Paris in 1983 and is known as human immunodeficiency virus 1 (HIV-1). HIV-1 is believed to have originated in Africa, where a related virus, HIV-2, was discovered in 1986 by the Pasteur Institute group. Both HIV-1 and HIV-2 are classed as retroviruses, because their genetic material is RNA rather than DNA. HIVs require a host cell to reproduce, and the hosts in humans are the so-called T4 lymphocytes, which are the cells primarily responsible for inducing the immune system to respond when provoked. The HIV penetrates the cell wall of a T4 lymphocyte and deposits both its RNA and an enzyme called reverse transcriptase inside the T4 cell, where the reverse transcriptase catalyzes the formation of a DNA strand that is complementary to the viral RNA. The transcribed DNA then serves as the template for formation of double-helical DNA, which, with the information it carries for reproduction of the HIV, becomes incorporated into the T4 cell s own genetic material. The viral DNA induces the host lymphocyte to begin producing copies of the virus, which then leave the host to infect other T4 cells. In the course of HIV reproduction, the ability of the T4 lymphocyte to reproduce itself is hampered. As the number of T4 cells decrease, so does the body s ability to combat infections. 

Rather uniquely, ICAM-1 is also subverted as receptor by human pathogens in at least three different ways. Major group rhinoviruses and A-type coxsackieviruses use ICAM-1 to release their RNA into the host cell cytoplasm. Erythrocytes infected by the malarial parasite Plasmodium falciparum, are able to bind ICAM-1 in the surface of endothelial cells (Berendt et al., 1992 Ockenhouse et al., 1992), and use this cytoadherence to sequester themselves in deep vascular beds, including the brain, minimizing exposure of the parasite to immune surveillance. Finally, human immunodeficiency virus-1 (HIV-1), uses ICAM-1 as a coreceptor (Bastiani et al., 1997 Fortin et al., 1997 Rizzuto and Sodroski, 1997). HIV-1 acquires several host cell membrane proteins when it buds from infected cells, making it possible for ICAM-1 to be incorporated into the envelope of the virions. This results in an increase of subsequent virus-cell interactions, enhancement of virus infectivity, and extension of the host cell range. 

FEP has been successfully used to calculate stability of mutant pro-teins, to examine solvation properties,and to predict relative free energies of enzyme—inhibitor binding in the human immunodeficiency virus 1 (HIV-1) protease system,... 

---