Liquid Chromatography-Mass Spectrometry Metabolomic Analysis of Terminalia ferdinandiana Exell. Fruit Extracts That Inhibit HIV-1 Cell Infection, HIV-1 Reverse Transcriptase and HIV-1 Protease
Abstract
:1. Introduction
2. Results
2.1. Rapid Screen for Antiviral Activity: Inhibition of MS2 Phage Replication
2.2. Inhibition of HIV-1 Reverse Transcriptase
2.3. Inhibition of HIV-1 Protease
2.4. Inhibition of HIV-1 Cell Infection
2.5. Quantification of Toxicity
2.6. HPLC-MS QTOF Analysis
3. Discussion
4. Materials and Methods
4.1. Materials
4.2. Plant Source and Extraction
4.3. MS2 Phage Plaque Reduction Assay for Detection of Anti-RNA Viral Activity
4.4. Inhibition of HIV-1 Reverse Transcriptase
4.4.1. mRNA Synthesis and Extraction
4.4.2. Reverse Transcriptase Assay
4.5. Inhibition of HIV-1 Protease
4.6. Inhibition of HIV-1 Infection in In Vitro Cell Assays
4.7. Toxicity Screening
4.7.1. Evaluation of Toxicity by Artemia franciscana Nauplii Bioassays (ALA)
4.7.2. Human Dermal Fibroblast (HDF) Cell Viability Assay
4.7.3. Therapeutic Index Evaluation
4.8. Non-Targeted Metabolomic HPLC-MS QTOF Profile Analysis
4.9. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Methanol Extract | Water Extract | Therapeutic Index | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
MS2 | HIV | MLV | MS2 | HIV | MLV | MS2 | HIV | MLV | |||||
M | W | M | W | M | W | ||||||||
Antiviral Assays | MS2 Viral replication | 68 | ND | ND | 44 | ND | ND | 13 | 22 | ND | ND | ND | ND |
Reverse transcriptase | ND | 35 | ND | ND | 33 | ND | ND | ND | 13 | 19 | ND | ND | |
Protease | ND | 19 | ND | ND | 27 | ND | ND | ND | 46 | 36 | ND | ND | |
Cell entry | ND | 16 | 9 | ND | 19 | 19 | ND | ND | 15 | 13 | 25 | 13 | |
Early phase replication in HEK293T cells | ND | 171 | ND | ND | 138 | ND | ND | ND | 0.7 | 1 | ND | ND | |
Toxicity | ALA toxicity | 875 | 983 | ||||||||||
HDF toxicity | - | - | |||||||||||
TZM-bl toxicity | 227 | >250 | |||||||||||
HEK293T toxicity | 112 | 138 |
Putative Identification | Empirical Formula | Retention Time | Molecular Mass | Relative Abundance (% Total Peak Area) | |
---|---|---|---|---|---|
Positive Ionisation Mode | Negative Ionisation Mode | ||||
Diethylstilbestrol monosulfate | C18H20O5S | 1.805 | 348.1036 | 0.12 | <0.1 |
Protocatechuic acid | C7H6O4 | 0.522 | 154.0272 | <0.1 | 2.34 |
Ellagic acid dihydrate | C14H10O10 | 1.085 | 338.0281 | 0.15 | <0.1 |
Gallic acid | C4H8O5 | 1.383 | 136.0374 | 4.3 | 4.7 |
Chebulic acid | C14H12O11 | 1.54 | 356.039 | 0.67 | 0.61 |
Pyrocatechol glucronide | C12H14O8 | 1.84 | 286.069 | 0.22 | <0.1 |
Ethyl gallate isomer 1 | C9H10O5 | 2.33 | 198.0529 | 0.04 | <0.1 |
Chlorogenic acid | C16H18O9 | 3.52 | 354.311 | 0.86 | <0.1 |
Ellagic acid | C14H6O8 | 4.277 | 285.1943 | 0.56 | 0.83 |
Ethyl gallate isomer 2 | C9H10O5 | 4.871 | 198.0529 | 0.14 | <0.1 |
Corilagin | C27H22O18 | 4.943 | 634.082 | <0.1 | 2.83 |
Ethyl gallate isomer 3 | C9H10O5 | 6.065 | 198.0529 | 0.17 | 1.24 |
Gallocatechin | C15H14O7 | 6.142 | 306.0768 | <0.1 | <0.1 |
Resveratrol | C14H12O3 | 6.235 | 228.2433 | 0.75 | <0.1 |
Resveratrol glucoside | C20 H22 O8 | 6.924 | 390.1333 | 0.11 | <0.1 |
Combretastastin A-1 | C18H20O6 | 6.94 | 332.1245 | 0.1 | <0.1 |
Combretastastin | C18H22O6 | 7.274 | 334.1403 | 0.16 | <0.1 |
Pentahydroxystilbene | C14H12O5 | 8.322 | 260.068 | 0.11 | <0.1 |
Luteolin | C21H20O11 | 8.345 | 448.1025 | 0.54 | <0.1 |
Castalagin | C41H26O26 | 7.015 | 934.0715 | 0.12 | <0.1 |
Rutin | C27H30O16 | 8.73 | 610.521 | 0.19 | <0.1 |
Chebulinic acid | C41H32O27 | 8.996 | 956.113 | 0.67 | <0.1 |
Exifone | C13H10O7 | 9.32 | 278.0433 | 1.62 | 2.26 |
Punicalin | C34H22O22 | 9.363 | 782.0621 | 0.165 | <0.1 |
Vitexin | C21H20O10 | 9.397 | 432.1064 | 5.59 | 0.77 |
Chebulagic acid | C41H30O27 | 9.878 | 954.0965 | <0.1 | 0.13 |
Quercetin | C15H10O7 | 11.293 | 302.0434 | 1.03 | 0.23 |
Trimethyl ellagic acid | C17H12O8 | 14.237 | 344.0538 | 0.17 | 1.07 |
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Cock, I.E.; Matthews, B.; Basson, A.E. Liquid Chromatography-Mass Spectrometry Metabolomic Analysis of Terminalia ferdinandiana Exell. Fruit Extracts That Inhibit HIV-1 Cell Infection, HIV-1 Reverse Transcriptase and HIV-1 Protease. Molecules 2025, 30, 1701. https://doi.org/10.3390/molecules30081701
Cock IE, Matthews B, Basson AE. Liquid Chromatography-Mass Spectrometry Metabolomic Analysis of Terminalia ferdinandiana Exell. Fruit Extracts That Inhibit HIV-1 Cell Infection, HIV-1 Reverse Transcriptase and HIV-1 Protease. Molecules. 2025; 30(8):1701. https://doi.org/10.3390/molecules30081701
Chicago/Turabian StyleCock, Ian Edwin, Benjamin Matthews, and Adriaan Erasmus Basson. 2025. "Liquid Chromatography-Mass Spectrometry Metabolomic Analysis of Terminalia ferdinandiana Exell. Fruit Extracts That Inhibit HIV-1 Cell Infection, HIV-1 Reverse Transcriptase and HIV-1 Protease" Molecules 30, no. 8: 1701. https://doi.org/10.3390/molecules30081701
APA StyleCock, I. E., Matthews, B., & Basson, A. E. (2025). Liquid Chromatography-Mass Spectrometry Metabolomic Analysis of Terminalia ferdinandiana Exell. Fruit Extracts That Inhibit HIV-1 Cell Infection, HIV-1 Reverse Transcriptase and HIV-1 Protease. Molecules, 30(8), 1701. https://doi.org/10.3390/molecules30081701