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: Calycosin, the major isoflavonoid found in Radix astragali, Trifolium pratense, and Astragalus Membranaceus (fisch)Bge, 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; (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, for the first time, a natural product-based antiviral therapy against RNA viruses such as HIV-1.
Calycosin, 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.
Thus, pharmacological formulations encompassing “Calycosin or its analogs either alone or in combination with other drugs “ may be used to inhibit HIV-1 production.
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 Calycosin increase the expression of Heme oxygenase-2 (HO-2)?
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Citation: Boominathan, L., Natural product-derived antiviral therapy for HIV virus: Calycosin, the major isoflavonoid found in Radix astragali, Trifolium pratense, and Astragalus Membranaceus (fisch)Bge, 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, 6/March/2017, 1o.34 pm, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org
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