What we say:
Dr L Boominathan PhD, Director-cum-chief Scientist of GBMD, reports that: Repurposing the analgesic agent Parecoxib into an anti-HIV agent: Parecoxib (trade name: Dynastat), a selective cox-2 (Cyclooxygenase-2) inhibitor, 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
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:
I had published earlier that aspirin, in conjunction with other agents, may function as an anti-infective agent–presented with detailed mechanistic insights– against a number of bacterial and viral infections. A recent study confirmed our findings and suggests that daily intake of aspirin (low dose) may protect against HIV1 infections. However, the mechanism of action remains unclear.
This study suggests an analgesic drug-based antiviral therapy against RNA viruses such as HIV-1. Parecoxib, 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 “Parecoxib or its analogs, either alone or in combination with other drugs,” may be used to inhibit HIV-1 production. Together, this study suggests that (1) Parecoxib may function as an anti-retroviral agent against HIV infections; and (2) daily intake of Parecoxib (low dose) may protect against HIV1 infections.
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 Parecoxib increase the expression of Heme oxygenase-2 (HO-2)?
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Citation: Boominathan, L., Repurposing the anti-analgesic agent Parecoxib into an anti-HIV agent: Parecoxib (trade name: Dynastat), a selective cox-2 (Cyclooxygease-2) inhibitor, 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, 11/october/2018, 12.14 am, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org
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