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Combinatorial therapy against HIV virus: Sodium butyrate 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, 21/June/2018, 10.10 am

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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:  Combinatorial therapy against HIV virus: Sodium butyrate 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. Sodium butyrate, 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 Sodium butyrate functions as an anti-HIV agent. Sodium butyrate inhibits HIV-1 budding and production via up-regulation of HO-2

Figure 2. The chemical structure of Sodium butyrate

 

 

 

 

 

 

 

 

 

Thus, pharmacological formulations encompassing “Sodium butyrate 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 Sodium butyrate increase the expression of Heme oxygenase-2 (HO-2)?

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References:

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

Citation: Boominathan, L., Antiviral therapy for HIV virus: Sodium butyrate 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, 21/June/2018, 10.10 am, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org

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