Avirulins, a Novel Class of HIV-1 Reverse Transcriptase Inhibitors Effective in the Female Reproductive Tract Mucosa
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cell Lines and Viruses
2.2. Collection of Human Specimens
2.3. TZM-bl Luciferase Infection Assay
2.4. In Silico Compound Screening
2.5. PM1 and PBMC Infection and p24
2.6. Cytotoxicity and Cell Viability
2.7. Reverse Transcriptase Inhibition Assay
2.8. Avirulin Antiviral Activity in Clarified Vaginal Fluid
3. Results
3.1. Antiviral and Structural Characteristics of Avirulins
3.2. Evaluation of Antiviral Activity in Lead Compounds
3.3. HIV-1 Reverse Transcriptase Inhibition of Avirulins
3.4. Inhibition in Genetically Variant HIV-1 Clades HIV
3.5. Evaluation in the Female Reproductive Tract
4. Discussion
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Compound | IUPAC | IC50 (uM) 1 | IC90 (uM) 1 |
---|---|---|---|
Av-5 | 3-[1-(1-methyl-1H-pyrazole-4-carbonyl)pyrrolidin-3-yl]-5-{2-[2-(trifluoromethyl)phenoxy]ethyl}-1H-pyrazole | 1.57 ± 0.42 | 8.41 ± 1.26 |
Av-26 | 2-methoxy-1-[3-(5-{2-[2-(trifluoromethyl)phenoxy]ethyl}-1H-pyrazol-3-yl)pyrrolidin-1-yl]ethan-1-one | 2.17 ± 0.30 | 15.9 ± 1.21 |
Av-27 | 3-(1-cyclohexanecarbonylpyrrolidin-3-yl)-5-{2-[3-(trifluoromethyl)phenoxy]ethyl}-1H-pyrazole | 2.30 ± 0.61 | 18.2 ± 1.61 |
Av-14 | 5-[2-(2-chlorophenoxy)ethyl]-3-[1-(1-methyl-1H-pyrazole-4-carbonyl)pyrrolidin-3-yl]-1H-pyrazole | 3.59 ± 0.45 | 18.65 ± 1.18 |
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Cherne, M.D.; Hall, J.; Kellner, A.; Chong, C.F.; Cole, A.L.; Cole, A.M. Avirulins, a Novel Class of HIV-1 Reverse Transcriptase Inhibitors Effective in the Female Reproductive Tract Mucosa. Viruses 2019, 11, 408. https://doi.org/10.3390/v11050408
Cherne MD, Hall J, Kellner A, Chong CF, Cole AL, Cole AM. Avirulins, a Novel Class of HIV-1 Reverse Transcriptase Inhibitors Effective in the Female Reproductive Tract Mucosa. Viruses. 2019; 11(5):408. https://doi.org/10.3390/v11050408
Chicago/Turabian StyleCherne, Michelle D., Jesse Hall, Alisha Kellner, Christine F. Chong, Amy L. Cole, and Alexander M. Cole. 2019. "Avirulins, a Novel Class of HIV-1 Reverse Transcriptase Inhibitors Effective in the Female Reproductive Tract Mucosa" Viruses 11, no. 5: 408. https://doi.org/10.3390/v11050408
APA StyleCherne, M. D., Hall, J., Kellner, A., Chong, C. F., Cole, A. L., & Cole, A. M. (2019). Avirulins, a Novel Class of HIV-1 Reverse Transcriptase Inhibitors Effective in the Female Reproductive Tract Mucosa. Viruses, 11(5), 408. https://doi.org/10.3390/v11050408