Natural product-derived antiviral therapy for HIV virus: Shikonin, isolated from Zicao (also known as Purple gromwell, the dried root of Lithospermum erythrorhizon), 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, 23/February/2017, 9.53 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-cum-chief Scientist of GBMD, reports that: Natural product-derived antiviral therapy for HIV virus: Shikonin, isolated from Zicao (also known as Purple gromwell, the dried root of Lithospermum erythrorhizon), 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


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; (3) the life-long painful drug treatment is required to treat HIV/AIDS and its associated opportunistic infections; (3) 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, for the first time, a natural product-based antiviral therapy against RNA viruses such as HIV-1.

Shikonin, 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.

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Thus, pharmacological formulations encompassing “Shikonin or its analogues or  Shikonin plus any of the known antiviral compounds” may be used to inhibit HIV-1 production.

Shikonin inhibits HIV1 production

Figure 1 Shikonin inhibits HIV-1 budding and production via up-regulation of HO-2


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 Shikonin increase the expression of Heme oxygenase-2 (HO-2)?

Amount: $500

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References:

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

Citation: Boominathan, L., Natural product-derived antiviral therapy for HIV virus: Shikonin, isolated from Zicao (also known as Purple gromwell, the dried root of Lithospermum erythrorhizon), 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, 23/February/2017, 9.53 pm, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org

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