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INFECTIOUS DISEASES / BASIC RESEARCH
Polyether antibiotics K-41A and K-41Am inhibit
HIV-1 replication via suppressing the activities of HIV-1 reverse transcriptase and integrase
1
Guangxi Key Laboratory of AIDS Prevention and Treatment & Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China
2
Guangxi Collaborative Innovation Centre for Biomedicine, Life Sciences Institute, Guangxi Medical University, Nanning, Guangxi, China
3
CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, RNAM Centre for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, Guangdong, China
Submission date: 2020-03-26
Final revision date: 2020-06-01
Acceptance date: 2020-06-13
Online publication date: 2020-08-11
Publication date: 2026-01-16
Corresponding author
Bo Zhou
Guangxi Collaborative Innovation Centre for Biomedicine Life Sciences Institute Guangxi Medical University, Nanning Guangxi, China
Guangxi Collaborative Innovation Centre for Biomedicine Life Sciences Institute Guangxi Medical University, Nanning Guangxi, China
Li Ye
Guangxi Collaborative Innovation Centre for Biomedicine Life Sciences Institute Guangxi Medical University, Nanning Guangxi, China
Guangxi Collaborative Innovation Centre for Biomedicine Life Sciences Institute Guangxi Medical University, Nanning Guangxi, China
Hao Liang
Guangxi Collaborative Innovation Centre for Biomedicine Life Sciences Institute Guangxi Medical University, Nanning Guangxi, China
Guangxi Collaborative Innovation Centre for Biomedicine Life Sciences Institute Guangxi Medical University, Nanning Guangxi, China
Arch Med Sci 2025;21(6):2680-2691
KEYWORDS
TOPICS
ABSTRACT
Introduction:
K-41A is a known compound with antibacterial activity against gram-positive bacteria and coccidia. In our screening of anti-HIV compounds, we found polyether antibiotic K-41A and its analogue K-41Am isolated from a marine-derived Streptomyces sp. SCSIO 01680 exhibited anti-HIV activity.
Material and methods:
In this study, we characterised the anti-HIV activity of K-41A and K-41Am as well as the mechanism(s) involved. The dose-dependent inhibitory effects of K-41A and K-41Am on HIV-1 replication were observed in the TZM-bl-HIV-1IIIB system, MT-2-HIV-1IIIB system, and peripheral blood mononuclear cells (PBMCs)-HIV-1BaL system. The 50% inhibitory concentrations (IC50) of K-41A on HIV-1 replication in three systems were 0.75 µM, 0.09 µM, and 0.13 µM, respectively, and the selective indexes (SIs) were 5.81, 49.44, and 598.00, respectively. The IC50 of K-41Am in three systems were 5.57 µM, 0.24 µM, and 1.15 µM, respectively, and the SIs were > 1.04, 80.71, and > 5.03, respectively.
Results:
Mechanism research demonstrates that two compounds inhibited the activities of HIV-1 reverse transcriptase (RT) and integrase (IN) in a dose-dependent manner. Molecular docking shows that the docking scores were relatively high between the compound and HIV-1 RT or IN.
Conclusions:
K-41A and K-41Am possess anti-HIV-1 activity via a multi-target inhibition mechanism, which provides a novel molecular pattern for anti-HIV drug design and structural modification to improve the anti-HIV activity.
K-41A is a known compound with antibacterial activity against gram-positive bacteria and coccidia. In our screening of anti-HIV compounds, we found polyether antibiotic K-41A and its analogue K-41Am isolated from a marine-derived Streptomyces sp. SCSIO 01680 exhibited anti-HIV activity.
Material and methods:
In this study, we characterised the anti-HIV activity of K-41A and K-41Am as well as the mechanism(s) involved. The dose-dependent inhibitory effects of K-41A and K-41Am on HIV-1 replication were observed in the TZM-bl-HIV-1IIIB system, MT-2-HIV-1IIIB system, and peripheral blood mononuclear cells (PBMCs)-HIV-1BaL system. The 50% inhibitory concentrations (IC50) of K-41A on HIV-1 replication in three systems were 0.75 µM, 0.09 µM, and 0.13 µM, respectively, and the selective indexes (SIs) were 5.81, 49.44, and 598.00, respectively. The IC50 of K-41Am in three systems were 5.57 µM, 0.24 µM, and 1.15 µM, respectively, and the SIs were > 1.04, 80.71, and > 5.03, respectively.
Results:
Mechanism research demonstrates that two compounds inhibited the activities of HIV-1 reverse transcriptase (RT) and integrase (IN) in a dose-dependent manner. Molecular docking shows that the docking scores were relatively high between the compound and HIV-1 RT or IN.
Conclusions:
K-41A and K-41Am possess anti-HIV-1 activity via a multi-target inhibition mechanism, which provides a novel molecular pattern for anti-HIV drug design and structural modification to improve the anti-HIV activity.
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