Natural Products and HIV/AIDS

Abstract

The study of natural products in biomedical research is not a modern concept. Many of the most successful medical therapeutics are derived from natural products, including those studied in the field of HIV/AIDS. Biomedical research has a rich history of discovery based on screens of medicinal herbs and traditional medicine practices. Compounds derived from natural products, which repress HIV and those that activate latent HIV, have been reported. It is important to remember the tradition in medical research to derive therapies based on these natural products and to overcome the negative perception of natural products as an "alternative medicine."

Keywords: AIDS; HIV; HIV reactivation; HIV suppression; natural products.

FIG. 1.

Natural products that suppress HIV replication. Natural product-derived compounds have been studied, which target multiple steps in HIV replication (A) Calanolide A/B, Tulsi/Holy Basil, Kuwanon-L, Rheum-palatum L, and Patentiflorin A inhibit HIV RT, blocking the reverse transcription of HIV genomic RNA into proviral DNA. (B) In addition to their anti-RT activity, Kuwanon-L and Rheum-palatum L have anti-IN activity, which prevents integration HIV proviral DNA into the host genome. (C) The soybean-derived Bowman-Birk inhibitor increases cellular expression of HIV restriction factors, RIG-I and Apobec3G, which also inhibit at the RT step. Additionally Bowman-Birk inhibitor also inhibits expression of inflammatory cytokines. (D) Betulinic acid inhibits HIV Gag processing and prevents release of infectious viral particles. IN, integrase; RT, reverse transcriptase.

FIG. 2.

Natural products that activate HIV transcription. Natural product-derived compounds have been studied, which reactivate latent HIV by inducing HIV transcription. (A) PKC agonist (bryostatin, prostratin, and ingenol), a crude extract of kansui and procyanidin, activate cellular NF-κB, which contributes to transcription initiation. (B) PKC agonist (bryostatin, prostratin, and ingenol), a crude extract of kansui, and procyanidin induce cellular expression of CycT1, part of the P-TEFb complex. (C) Increase in total CycT1 permits HDACi and BET-bromodomain inhibitors to function by activating P-TEFb and releasing it from its inactive complex with Hexim1:7SK. Altogether, increase in expression and release of free P-TEFb allow recruitment of P-TEFb to NF-κB and POLII, resulting in transcription elongation. (D) A crude extract of kansui further reactivates latent HIV by increasing cellular expression of CDK11, which complexes with CycL to promote cleavage and polyadenylation (CPA) recruitment and proper mRNA end processing. NF-κB, nuclear factor kappa B; PKC, protein kinase C; P-TEFb, positive transcription elongation factor b.