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Activity of human immunodeficiency virus type 1 protease inhibitors against the initial autocleavage in Gag-Pol polyprotein processing


, : Activity of human immunodeficiency virus type 1 protease inhibitors against the initial autocleavage in Gag-Pol polyprotein processing. Antimicrobial Agents and ChemoTherapy 56(7): 3620-3628

Inhibitors of HIV protease have proven to be important drugs in combination anti-HIV therapy. These inhibitors were designed to target mature protease and prevent viral particle maturation by blocking Gag and Gag-Pol processing by mature protease. Currently there are few data assessing the ability of these protease inhibitors to block the initial step in autoproteolytic processing of Gag-Pol. This unique step involves the dimerization of two Gag-Pol polyproteins and autocleavage of the Gag-Pol polyprotein by the embedded dimeric protease. We developed a plasmid encoding a modified form of Gag-Pol that can undergo autoprocessing only at the initial cleavage site between p2 and nucleocapsid. Using an in vitro transcription/translation system, we assessed the ability of six different approved protease inhibitors (darunavir, indinavir, nelfinavir, ritonavir, saquinavir, and tipranavir) to block this initial autocleavage step. Of these inhibitors, darunavir and saquinavir were the most effective. Darunavir and saquinavir were also the most effective at blocking the initial autoprocessing of full-length Gag-Pol in HIV-1-infected T cells. Thus, we have identified at least two HIV-1 protease inhibitors that have activity against the primary autocatalytic step of the embedded HIV-1 protease in Gag-Pol at concentrations that may be attained in HIV-1-infected patients. Due to unique aspects of the initial processing step, it may be possible to develop inhibitors with greater potency against this step, thus halting viral maturation at the earliest stages. The transcription/translation assay could be used to develop more potent inhibitors of this essential first step in viral maturation.

US$19.90

PMID: 22508308

DOI: 10.1128/AAC.00055-12


Other references

Houston, J.B.; Wilkens, H.J.; Levy, G., 1976: Potentiation of isoproterenol effect by ascorbic acid. Intraduodenal administration of isoproterenol together with ascorbic acid caused a much greater increase in the heart rate and pulse pressure, and a greater decrease in the mean blood pressure of anesthetized dogs than was observed after intraduod...

Arscott, S.A.; Simon, P.W.; Tanumihardjo, S.A., 2010: Anthocyanins in purple-orange carrots (Daucus carota L.) do not influence the bioavailability of beta-carotene in young women. Purple carrots contain anthocyanins in addition to the provitamin A carotenoids in typical orange carrots. Simultaneous consumption of these phytochemicals in carrots may affect the bioavailability of carotenoids. The bioavailability of beta-carot...

W.R.C.rr; M.G.lfand, 1960: The biochemistry of the African in Southern Rhodesia I The serum proteins of new born African infants in Salisbury. Samples of cord blood were studied from newborn children, African 28 male and 26 female and European, 6 male and 5 female. Estimations were of total protein, albumin and globulin by chemical methods and of albumin and fractions of globulin by zone...

Barratt B.C., 1988: Micromorphology and pedogenesis in a late Pleistocene succession of tephric loesses and Paleosols near Tapapa, Mamaku Plateau, North Island, New Zealand. Pages 7-8 1988

Alvarez, Fernando, 1999: Shape, growth, and evolution of the brachio-jugal system developed by the retziidines. Phylogenetic and ontogenetic variation in the brachio-jugal system, inter-population and intra-population variation, and the structural relationship between the brachidium and crura are probed on the basis of more than 1000 specimens of silicified...

Wee, C.Ling.; Gavaghan, D.; Sansom, M.S.P., 2010: Interactions between a voltage sensor and a toxin via multiscale simulations. Gating-modifier toxins inhibit voltage-gated ion channels by binding the voltage sensors (VS) and altering the energetics of voltage-dependent gating. These toxins are thought to gain access to the VS via the membrane (i.e., by partitioning from w...

Wong, Y.H.; Demoliou-Mason, C.D.; Hanley, M.R.; Barnard, E.A., 1990: Agonist selective protection of the opioid receptor coupled g proteins from inactivation by 5' p fluorosulfonylbenzoylguanosine. The guanine nucleotide analogue, 5'-p-fluorosulphonylbenzoyl guanosine (FSBG), can react covalently with GTP-binding proteins (G proteins). In rat brain membranes, FSBG causes a time-dependent loss of .beta.,.gamma.-imido[8-3H]guanosine 5&apo...

Yoshimura, E.; Yano, T.; Ichinose, K.; Ushijima, K., 2005: Airway obstruction involving a laryngeal mask airway during arthroscopic shoulder surgery. Several earlier reports have described life-threatening airway obstruction during arthroscopic shoulder surgery performed under regional anesthesia, caused by the leakage of irrigation fluid out of the shoulder joint space into the surrounding sof...

Takeda, H.; Matsumura, Y.; Kuwata, S.; Nakano, H.; Shanmai, J.; Qiyan, Z.; Yufen, C.; Kusuoka, H.; Matsuoka, M., 2004: An assessment of PKI and networked electronic patient record system: lessons learned from real patient data exchange at the platform of OCHIS (Osaka Community Healthcare Information System). To enhance medical cooperation between the hospitals and clinics around Osaka local area, the healthcare network system, named Osaka Community Healthcare Information System (OCHIS), was established with support of a supplementary budget from the J...

Buckstein, R.; Imrie, K.; Spaner, D.; Potichnyj, A.; Robinson, J.B.; Nanji, S.; Pennel, N.; Reis, M.; Pinkerton, P.; Dube, I.; Hewitt, K.; Bernstein, N.L., 1998: The effects of in vivo purging with Rituxan on stem cell mobilization efficacy, harvest purity, cytokine profile and engraftment in patients with relapsed follicular lymphoma undergoing autologous stem cell transplant. Blood 92(10 SUPPL 1 PART 1-2): 647A, Nov 15