HPLC-Based Purification and Isolation of Potent Anti-HIV and Latency Reversing Daphnane Diterpenes from the Medicinal Plant Gnidia sericocephala ( Thymelaeaceae ).

Autor: Tembeni B; Department of Chemistry, University of Pretoria, Pretoria 0028, South Africa., Sciorillo A; The Wistar Institute, Philadelphia, PA 19104, USA., Invernizzi L; Department of Chemistry, University of Pretoria, Pretoria 0028, South Africa., Klimkait T; Molecular Virology, Department of Biomedicine, University of Basel, 4031 Basel, Switzerland., Urda L; Molecular Virology, Department of Biomedicine, University of Basel, 4031 Basel, Switzerland., Moyo P; Department of Chemistry, University of Pretoria, Pretoria 0028, South Africa., Naidoo-Maharaj D; Department of Chemistry, University of Pretoria, Pretoria 0028, South Africa.; Agricultural Research Council-Vegetables, Industrial and Medicinal Plants, Private Bag X293, Pretoria 0001, South Africa., Levitties N; The Wistar Institute, Philadelphia, PA 19104, USA., Gyampoh K; The Wistar Institute, Philadelphia, PA 19104, USA., Zu G; The Wistar Institute, Philadelphia, PA 19104, USA., Yuan Z; The Wistar Institute, Philadelphia, PA 19104, USA., Mounzer K; Jonathan Lax Immune Disorders Treatment Center, Philadelphia Fight Community Health Centers, Philadelphia, PA 19107, USA., Nkabinde S; Ungangezulu Indigenous Remedies, J Uitval, Wasbank 2920, South Africa., Nkabinde M; Ungangezulu Indigenous Remedies, J Uitval, Wasbank 2920, South Africa., Gqaleni N; Africa Health Research Institute, Congella 4013, South Africa.; Discipline of Traditional Medicine, University of KwaZulu-Natal, Durban 4001, South Africa.; Faculty of Health Sciences, Durban University of Technology, Durban 4001, South Africa., Tietjen I; The Wistar Institute, Philadelphia, PA 19104, USA., Montaner LJ; The Wistar Institute, Philadelphia, PA 19104, USA., Maharaj V; Department of Chemistry, University of Pretoria, Pretoria 0028, South Africa.
Jazyk: angličtina
Zdroj: Viruses [Viruses] 2022 Jun 30; Vol. 14 (7). Date of Electronic Publication: 2022 Jun 30.
DOI: 10.3390/v14071437
Abstrakt: Despite the success of combination antiretroviral therapy (cART), HIV persists in low- and middle-income countries (LMIC) due to emerging drug resistance and insufficient drug accessibility. Furthermore, cART does not target latently-infected CD4+ T cells, which represent a major barrier to HIV eradication. The “shock and kill” therapeutic approach aims to reactivate provirus expression in latently-infected cells in the presence of cART and target virus-expressing cells for elimination. An attractive therapeutic prototype in LMICs would therefore be capable of simultaneously inhibiting viral replication and inducing latency reversal. Here we report that Gnidia sericocephala, which is used by traditional health practitioners in South Africa for HIV/AIDS management to supplement cART, contains at least four daphnane-type compounds (yuanhuacine A (1), yuanhuacine as part of a mixture (2), yuanhuajine (3), and gniditrin (4)) that inhibit viral replication and/or reverse HIV latency. For example, 1 and 2 inhibit HIV replication in peripheral blood mononuclear cells (PBMC) by >80% at 0.08 µg/mL, while 1 further inhibits a subtype C virus in PBMC with a half-maximal effective concentration (EC50) of 0.03 µM without cytotoxicity. Both 1 and 2 also reverse HIV latency in vitro consistent with protein kinase C activation but at 16.7-fold lower concentrations than the control prostratin. Both 1 and 2 also reverse latency in primary CD4+ T cells from cART-suppressed donors with HIV similar to prostratin but at 6.7-fold lower concentrations. These results highlight G. sericocephala and components 1 and 2 as anti-HIV agents for improving cART efficacy and supporting HIV cure efforts in resource-limited regions.
Databáze: MEDLINE
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