APITOXINA & SIDA
| 1: Ann N Y Acad Sci. 2005 Nov;1056:279-92. |
Novel Drugs
and Vaccines Based on the Structure and Function of HIV Pathogenic Proteins
Including Nef.
Azad
AA.
Faculty of Health Sciences, Medical School, University of Cape Town, Anzio Road, Observatory, 7925, Cape Town, South Africa. a_azad05@yahoo.com.au.
Evidence is presented to suggest that HIV-1 accessory protein Nef could be involved in AIDS pathogenesis. When present in
extracellular medium, Nef
causes the death of a wide variety of cells in vitro and may therefore be
responsible for the depletion of bystander cells in lymphoid tissues during
HIV infection. When present inside the cell, Nef
could prevent the death of infected cells and thereby contribute to increased
viral load. Intracellular Nef does this by preventing
apoptosis of infected cells by either inhibiting proteins involved in apoptosis
or preventing the infected cells from being recognized by CTLs.
Neutralization of extracellular Nef
could prevent the death of uninfected immune cells and thereby the destruction
of the immune system. Neutralization of intracellular Nef
could hasten the death of infected cells and help reduce the viral load. Nef is therefore a very important molecular target for developing
therapeutics that slow progression to AIDS. The N-terminal region of Nef
and the naturally occurring bee venom mellitin have very similar primary and tertiary structures,
and they both act by destroying membranes. Chemical analogs
of a mellitin inhibitor prevent Nef-mediated
cell death and inhibit the interaction of Nef with
cellular proteins involved in apoptosis. Naturally occurring bee propolis also contains substances that prevent Nef-mediated cell lysis and increases
proliferation of CD4 cells in HIV-infected cultures. These chemical compounds
and natural products are water soluble and nontoxic
and are therefore potentially very useful candidate drugs.
PMID: 16387695 [PubMed
- in process]
| 2: Mol Pharmacol. 2001 Aug;60(2):341-7. |
A peptide
derived from bee venom-secreted phospholipase A2
inhibits replication of T-cell tropic HIV-1 strains via interaction with the
CXCR4 chemokine receptor.
Fenard D, Lambeau
G, Maurin T, Lefebvre
JC, Doglio A.
Laboratoire de Virologie, Institut National de la Sante
et de
PMID: 11455021 [PubMed
- indexed for MEDLINE]
| 3: Posit Aware. 1997 Mar-Apr;8(2):28-35. |
Whole body health.
Austin
E.
AIDS: Alternative therapies, widely used by Americans, include yoga, relaxation
techniques, and herbal medications, as well as less conventional and more
experimental treatments. The AIDS Research Center
in Seattle is conducting the largest study of alternative therapies. Many
alternative therapies are used as complements to traditional treatments, and
can make a disease easier to manage. Several categories of alternative medicines
are detailed: acupuncture and other Chinese treatments, natural treatments
including herbal medicine and aromatherapy, and mind-body treatments such
as hypnosis and biofeedback. Patients are cautioned to avoid five dangerous
therapies: chelation therapy, colonic irrigation,
bee venom therapy, hydrogen peroxide injections, and unlabeled medicines.
Contact telephone numbers for alternative therapies are listed.
Publication Types:
PMID: 11364455 [PubMed - indexed for MEDLINE]
| 4: Med Res Rev. 2000 Sep;20(5):323-49. |
Current lead natural products for the chemotherapy of human immunodeficiency
virus (HIV) infection.
De Clercq
E.
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium. erik.declerq@rega.kuleven.ac.be
A large variety of natural products have been described as anti-HIV agents,
and for a portion thereof the target of interaction has been identified. Cyanovirin-N, a 11-kDa protein from Cyanobacterium
(blue-green alga) irreversibly inactivates HIV and also aborts cell-to-cell
fusion and transmission of HIV, due to its high-affinity interaction with
gp120. Various sulfated polysaccharides extracted
from seaweeds (i.e., Nothogenia fastigiata,
Aghardhiella tenera) inhibit
the virus adsorption process. Ingenol derivatives
may inhibit virus adsorption at least in part through down-regulation of CD4
molecules on the host cells. Inhibition of virus adsorption by flavanoids
such as (-)epicatechin and its 3-O-gallate has been attributed to an
irreversible interaction with gp120 (although these compounds are also known
as reverse transcriptase inhibitors). For the triterpene
glycyrrhizin (extracted from the licorice root Glycyrrhiza radix) the mode of anti-HIV action may at least
in part be attributed to interference with virus-cell binding. The mannose-specific
plant lectins from Galanthus, Hippeastrum, Narcissus, Epipac
tis helleborine, and Listera ovata, and the N-acetylgl ucosamine-specific lectin from Urtica dioica would primarily be targeted at the virus-cell fusion
process. Various other natural products seem to qualify as HIV-cell fusion
inhibitors: the siamycins [siamycin
I (BMY-29304), siamycin II (RP 71955, BMY 29303),
and NP-06 (FR901724)] which are tricyclic 21-amino-acid
peptides isolated from Streptomyces spp that differ from one another only at position 4 or 17
(valine or isoleucine in each case);
the betulinic acid derivative RPR 103611, and the
peptides tachyplesin and polyphemusin
which are highly abundant in hemocyte debris of
the horseshoe crabs Tachypleus tridentatus
and Limulus polyphemus, i.e., the 18-amino-acid
peptide T22 from which T134 has been derived. Both T22 and T134 have been
shown to block T-tropic X4 HIV-1 strains through a specific antagonism with
the HIV corecept or CXCR4. A number of natural products have been
reported to interact with the reverse transcriptase, i.e., baicalin,
avarol, avarone, psychotrine, phloroglucinol derivatives,
and, in particular, calanolides (from the tropical
rainforest tree, Calophyllum lanigerum) and inophyllums (from
the Malaysian tree, Calophyllum inophyllum).
The natural marine substance illimaquinone would
be targeted at the RNase H function of the reverse
transcriptase. Curcumin (diferuloylmethane,
from turmeric, the roots/rhizomes of Curcuma spp),
dicaffeoylquinic and dicaffeoylt
artaric acids, L-chicoric acid,
and a number of fungal metabolites (equisetin, phomasetin, oteromycin, and integric acid) have all been proposed as HIV-1 integrase inhibitors. Yet, we have recently shown that L-c
hicoric acid owes its anti-HIV activity to a specific interaction
with the viral envelope gp120 rather than integrase.
A number of compounds would be able to inhibit HIV-1 gene expression at the
transcription level: the flavonoid chrysin
(through inhibition of casein kinase II, the antibacter ial peptides melittin (from bee venom) and cecropin,
and EM2487, a novel substance produced by Streptomyces.
(ABSTRACT TRUNCATED)
Publication Types:
· Review
PMID: 10934347 [PubMed - indexed for MEDLINE]
| 5: AIDS Res Hum Retroviruses. 1997 Nov 20;13(17):1525-32. |
A synthetic peptide
corresponding to the carboxy terminus of human immunodeficiency
virus type 1 transmembrane glycoprotein induces
alterations in the ionic permeability of Xenopus laevis oocytes.
Comardelle AM, Norris
CH, Plymale DR, Gatti PJ, Choi B, Fermin CD, Haislip AM, Tencza SB, Mietzner TA, Montelaro RC, Garry
RF.
Graduate Program in Molecular and Cellular Biology,
The carboxy-terminal 29 amino acids of the human
immunodeficiency virus type 1 transmembrane glycoprotein
(HIV-1 TM) are referred to as lentivirus lytic
peptide 1 (LLP-1). Synthetic peptides corresponding to LLP-1 have been shown
to induce cytolysis and to alter the permeability of cultured cells to various
small molecules. To address the mechanisms by which LLP-1 induces cytolysis
and membrane permeability changes, various concentrations of LLP-1 were incubated
with Xenopus laevis oocytes,
and two-electrode, voltage-clamp recording measurements were performed. LLP-1
at concentrations of 75 nM and above induced dramatic
alterations in the resting membrane potential and ionic permeability of Xenopus oocytes. These concentrations
of LLP-1 appeared to induce a major disruption of plasma membrane electrophysiological
integrity. In contrast, concentrations of LLP-1 of 20-50 nM induced changes in membrane ionic permeability that mimic
changes induced by compounds, such as the bee venom peptide melittin, that are known to form channel-like structures in
biological membranes at sublytic concentrations.
An analog of LLP-1 with greatly reduced cytolytic
activity failed to alter the electrophysiological properties of Xenopus oocytes. Thus, by altering
plasma membrane ionic permeability, the carboxy
terminus of TM may contribute to cytolysis of HIV-1-infected CD4+ cells.
Publication Types:
· Review
PMID: 9390752 [PubMed - indexed for MEDLINE]
| 6: Protein Sci. 1992 Nov;1(11):1454-64. |
A molecular model for membrane fusion based on solution studies
of an amphiphilic peptide from HIV gp41.
Fujii G, Horvath
S, Woodward
S, Eiserling F, Eisenberg
D.
Molecular Biology Institute, University of California, Los Angeles 90024-1570.
The mechanism of protein-mediated membrane fusion and lysis
has been investigated by solution-state studies of the effects of peptides
on liposomes. A peptide (SI) corresponding to a highly amphiphilic C-terminal segment from the envelope protein (gp41)
of the human immunodeficiency virus (HIV) was synthesized and tested for its
ability to cause lipid membranes to fuse together (fusion) or to break open
(lysis). These effects were compared to those produced
by the lytic and fusogenic
peptide from bee venom, melittin. Other properties
studied included the changes in visible absorbance and mean particle size,
and the secondary structure of peptides as judged by CD spectroscopy. Taken
together, the observations suggest that protein-mediated membrane fusion is
dependent not only on hydrophobic and electrostatic forces but also on the
spatial arrangement of the amino acid residues to form an amphiphilic
structure that promotes the mixing of the lipids between membranes. A speculative
molecular model is proposed for membrane fusion by alpha-helical peptides,
and its relationship to the forces involved in protein-membrane interactions
is discussed.
PMID: 1303764 [PubMed
- indexed for MEDLINE]