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Updated: Dec 17, 2025

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
The New NNRTI ACC007 Combined with Lamivudine and Tenofovir Disoproxil Fumarate Show Synergy Anti-HIV Activity In
Xu-Sheng Huang1,2, Rong-Hua Luo1, Xiong-Lin Hu3
1Key Laboratory of Bioactive Peptides of Yunnan Province/Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China
Background:
Acquired immunodeficiency syndrome can hardly be cured currently and people with human immunodeficiency virus (HIV) need lifelong treatment that may result in the emergence of drug resistance which leads to failed treatment. Thus, the development of new anti- HIV drugs and new treatment regimens are necessary.
Objective:
The aim of this study is to analyze the combined anti-HIV activity of tenofovir disoproxil fumarate, lamivudine and ACC007, a new non-nucleoside reverse transcriptase inhibitor.
Methods:
The antiviral activity of tenofovir disoproxil fumarate, lamivudine and ACC007 alone or in combination against different HIV-1 strains was determined by the detection of HIV-1 p24 level through enzyme-linked immunosorbent assay.
Result:
ACC007 showed EC50 of nanomolar range (from 3.03 nM to 252.59 nM) against all HIV-1 strains used in this study except the HIV-1A17, with EC50 of 1.57 μM. The combined antiviral activity of ACC007, lamivudine and tenofovir disoproxil fumarate showed synergy antiviral activity against all HIV-1 strains used in this study. The three-drug combination showed moderate synergism against HIV-1A17, HIV-14755-5, HIV-1K103N and HIV-1V106M, with a combination index value ranging from 0.71 to 0.87, and showed synergism against the other HIV-1 strains with combination index value from 0.35 to 0.67. The combination with ACC007 significantly increases the dose reduction index value of lamivudine and tenofovir disoproxil fumarate, compared with two-drug combination.
Conclusion:
ACC007 exhibits potent antiviral activity alone or with 3TC and TDF, and exerts synergistic effect against all HIV strains used in our investigation in vitro.
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