A method of inhibiting HIV replication
A technology of compounds and derivatives, applied in the field of inhibiting or treating HIV infection, can solve problems such as adverse side effects
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Embodiment 1
[0026] Example 1: Application of AICAR to Inhibit HIV Replication in Immortalized Cell Lines
[0027] The U1 cell line is an immortalized human monocytic cell line chronically infected with HIV. The viral genome inserts into the host cell DNA and can be activated by treatment with cytokines or sodium chloride. Activation leads to gene transcription and translation of the virus, producing virile particles that can be measured using an ELISA that enables quantitative detection of the virus' peptides, P24.
[0028] Cells from the U1 cell line (provided from Professor Lyn Morris, National Institute of Communicable Diseases, Johannesburg) were plated in 24-well plates at a concentration of one million cells per milliliter Cultivate, 0.5 milliliters in every hole, wherein the concentration of sodium chloride is 60mmol / l, different AICAR (from the Sigma-Aldrich company of U.S. St. Louis (St Louis, MO, USA) MO) concentration (0.1,0.2,0.35 , 0.4mmol / l). After 3 days of incubation at...
Embodiment 2
[0031] Example 2: Application of Metformin to Inhibit HIV Replication in Immortalized Cell Lines
[0032] The procedure described in Example 1 was repeated except that 0, 4, 8 or 16 mmol / l of metformin hydrochloride (supplied by Sigma-Aldrich, St. Louis, MO, USA) was added to the cell culture medium.
[0033] result
[0034] The levels of P24 obtained in each of the samples in the above examples are expressed as a percentage of the value obtained for the control sample (the value is assumed to be 100%). Table 1 lists the results of Examples 1 and 2.
[0035] Table 1: P24 levels in HIV-positive cells treated with AICAR or metformin
[0036] Experimental conditions
Number of experiments
Average P24 level (%)
control
6
100±0
AICAR 0.1mM
5
123±53
AICAR 0.2mM
6
52±31 *
AICAR 0.35mM
6
16±10 *
AICAR 0.4mM
6
14±12 *
Metformin 4mM
5
48±13 *
Met...
Embodiment 3 and 4
[0039] Examples 3 and 4: Use of AICAR and Metformin to Inhibit HIV Replication in Isolated Human Peripheral Blood Mononuclear Cells
[0040] The experiments described in Examples 1 and 2 were performed using isolated human peripheral blood mononuclear cells (PBMCs) cultured in the presence of human immunodeficiency virus instead of immortalized cell lines. This system is closer to the in vivo environment than the systems described in Examples 1 and 2. The results obtained in this system are basically the same as those seen in Table 1, both AICAR and metformin can completely inhibit HIV replication.
[0041] Applicants envisage that the same or similar results should be obtained when activators of human AMPK, in particular AICAR and / or metformin, are administered. Activation of AMPK is believed to result in a decrease in nuclear factor kappa-B (NF-κB) activity. Although human clinical trials are still required, it is conceivable that doses of metformin and / or AICAR required t...
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