Anti-HIV therapy: A pharmaceutical mixture encompassing etoposide and idasanutlin(ESIA) 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 upregulation of its target gene, 13/March/2019, 10.39 pm

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What we say:

Dr L Boominathan PhD, Director-cum-chief Scientist of GBMD, reports that: Anti-HIV therapy: A pharmaceutical mixture encompassing etoposide and idasanutlin(ESIA) 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 upregulation 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.


Research findings to Therapeutic opportunity:

This study suggests a combinatorial therapy for RNA viruses such as HIV-1.  A pharmaceutical mixture encompassing etoposide and idasanutlin (ESIA), 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 (fig.2).

Thus, pharmacological formulations encompassing “etoposide and idasanutlin (ESIA) or their analogs, either alone or in combination with other drugs,” may be used to inhibit HIV-1 production. Together, this study suggests that pharmacological formulations encompassing   etoposide and idasanutlin (ESIA) may function as an antiretroviral agent against HIV infections.

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

Figure 2. A pharmaceutical mixture encompassing etoposide and idasanutlin(ESIA) functions as an anti-HIV agent.through induction of its target gene HO-2 

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Details of the research findings:

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

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Undisclosed mechanistic information: How does a pharmaceutical mixture encompassing etoposide and idasanutlin(ESIA) 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., Anti-HIV therapy: A pharmaceutical mixture encompassing etoposide and idasanutlin(ESIA) 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 upregulation of its target gene, 13/March/2019, 10.39 pm, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org

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