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Antiviral therapy for HIV virus: 9-Aminoacridine increases Heme oxygenase 2 (HO-2) expression, blocks N-myristoylation of HIV-1 Gag protein, disrupts HIV-1 budding, and restricts HIV-1 production via up regulation of its target gene, 30/March/2018, 11.06 pm

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Introduction: What they say

A study from the Department of Biochemistry and Molecular Biophysics and Department of Microbiology and Immunology, Howard Hughes Medical Institute, Columbia University, New York, NY 10032, USA shows that “Heme Oxygenase 2 Binds Myristate to Regulate Retrovirus Assembly and TLR4 Signaling.” This research paper was published in the 8 February 2017 issue of the journal “Cell Host and microbe” [One of the best research journals in Infectious biology with an I.F of 12.552] by  Prof. Goff SP, Zhu Y and others.


What we say:

On the foundation of this interesting finding, Dr L Boominathan PhD, Director-Price 100cum-chief Scientist of GBMD, reports that:  Antiviral therapy for HIV virus: 9-Aminoacridine increases Heme oxygenase 2 (HO-2) expression, blocks N-myristoylation of HIV-1 Gag protein, disrupts HIV-1 budding, and restricts HIV-1 production via up regulation of its target gene

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From Significance of the study to Public health relevance:

Given that: (1) more than 37 million people worldwide are living with HIV/AIDS; (2) there is no effective vaccine available for HIV/AIDS; (3) HIV/AIDS tops the list of incurable diseases in humans; (4) the life-long painful drug treatment is required to treat HIV/AIDS and its associated opportunistic infections; (5) the global economic cost spent for HIV treatment is enormous, there is an urgent need to find: (i) a way to restore CD4 T-cells that were lost in HIV/AIDS; (ii) a cheaper alternative to the existing expensive antiviral drugs; (iii) a side-effect-free natural product-based drug; and (iv) a way to cure, not just treat, HIV-1/AIDS.


What is known?

Prof. Goff’s research team has recently shown that HO-2: a) binds the myristate moiety of HIV-1 Gag protein; b) inhibits virus budding; c) binds TRAM, the adaptor protein of Toll-like receptor 4 (TLR4); d) decreases sensitivity to TLR4 ligand lipopolysaccharide; e) negatively regulates TLR4 signalling; and f) inhibits HIV-1 and MLV virions production, suggesting that increasing the expression of HO-2 in HIV-1 infected individuals may inhibit HIV-1 production; and host inflammatory responses.


From Research findings to Therapeutic opportunity:

This study suggests a small molecule-based antiviral therapy against RNA viruses such as HIV-1.

9-Aminoacridine, by increasing the expression of its target gene, it may increase the expression of Heme oxygenase-2 (HO-2) (Figure 1). Thereby, it may: (1) bind and block the myristate moiety of HIV-1 Gag protein; (2) disrupt HIV-1 budding; (3) restrict HIV-1 infectivity, replication and production; (4) promote clearance of HIV-1 and MLV virions; and (5) strengthen antiviral immunity against RNA viruses.

Figure 1 Mechanistic insights into how 9-Aminoacridine functions as an anti-HIV agent. 9-Aminoacridine inhibits HIV-1 budding and production via up-regulation of HO-2

Figure 2. The chemical structure of 9-Aminoacridine

Thus, pharmacological formulations encompassing 9-Aminoacridine or its analogs, either alone or in combination with other drugs” may be used to inhibit HIV-1 production.

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Details of the research findings:

Idea Proposed/Formulated (with experimental evidence) by: Dr L Boominathan Ph.D.

Terms & Conditions apply http://genomediscovery.org/registration/terms-and-conditions/

Undisclosed mechanistic information: How does 9-Aminoacridine increase the expression of Heme oxygenase-2 (HO-2)?

Amount: $100#

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References:

Web: http://genomediscovery.org or http://newbioideas.com/

Citation: Boominathan, L., Antiviral therapy for HIV virus: 9-Aminoacridine increases Heme oxygenase 2 (HO-2) expression, blocks N-myristoylation of HIV-1 Gag protein, disrupts HIV-1 budding, and restricts HIV-1 production via up regulation of its target gene, 30/March/2018, 11.08 pm, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org

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