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Tytuł pozycji:

Anti-HIV Potential of Beesioside I Derivatives as Maturation Inhibitors: Synthesis, 3D-QSAR, Molecular Docking and Molecular Dynamics Simulations.

Tytuł:
Anti-HIV Potential of Beesioside I Derivatives as Maturation Inhibitors: Synthesis, 3D-QSAR, Molecular Docking and Molecular Dynamics Simulations.
Autorzy:
Zhao Z; Beijing Key Laboratory of New Drug Discovery Based on Classic Chinese Medicine Prescription, Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China.
Ma Y; Beijing Key Laboratory of New Drug Discovery Based on Classic Chinese Medicine Prescription, Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China.
Li X; Beijing Key Laboratory of New Drug Discovery Based on Classic Chinese Medicine Prescription, Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China.
Morris-Natschke SL; Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA.
Sun Z; Beijing Key Laboratory of New Drug Discovery Based on Classic Chinese Medicine Prescription, Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China.
Sun Z; Beijing Key Laboratory of New Drug Discovery Based on Classic Chinese Medicine Prescription, Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China.
Ma G; Beijing Key Laboratory of New Drug Discovery Based on Classic Chinese Medicine Prescription, Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China.
Dong Z; Beijing Key Laboratory of New Drug Discovery Based on Classic Chinese Medicine Prescription, Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China.
Zhao X; Beijing Key Laboratory of New Drug Discovery Based on Classic Chinese Medicine Prescription, Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China.
Yang M; Beijing Key Laboratory of New Drug Discovery Based on Classic Chinese Medicine Prescription, Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China.
Xu X; Beijing Key Laboratory of New Drug Discovery Based on Classic Chinese Medicine Prescription, Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China.
Lee K; Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA.
Wu H; Beijing Key Laboratory of New Drug Discovery Based on Classic Chinese Medicine Prescription, Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China.; Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA.
Chen C; Antiviral Drug Discovery Laboratory, Surgical Oncology Research Facility, Duke University Medical Center, Durham, NC 27710, USA.
Źródło:
International journal of molecular sciences [Int J Mol Sci] 2023 Jan 11; Vol. 24 (2). Date of Electronic Publication: 2023 Jan 11.
Typ publikacji:
Journal Article
Język:
English
Imprint Name(s):
Original Publication: Basel, Switzerland : MDPI, [2000-
MeSH Terms:
Virus Replication*
Anti-HIV Agents*/pharmacology
Anti-HIV Agents*/chemistry
Molecular Docking Simulation ; Molecular Dynamics Simulation ; Quantitative Structure-Activity Relationship ; Capsid Proteins/chemistry
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Grant Information:
CIFS 2021-I2M-1-071 the CAMS Innovation Fund for Medical Sciences; No. 2020JJ4493 Natural Science Foundation of Hunan Province of China; No. YYZW2019-36 the Foundation of Hunan Double First-rate Discipline Construction Projects of Bioengineering
Contributed Indexing:
Keywords: 3D-QSAR; CA-SP1; anti-HIV; beesioside I; maturation inhibitor; molecular docking; molecular dynamics simulations
Substance Nomenclature:
0 (beesioside I)
S125DW66N8 (bevirimat)
0 (Capsid Proteins)
0 (Anti-HIV Agents)
Entry Date(s):
Date Created: 20230121 Date Completed: 20230124 Latest Revision: 20230308
Update Code:
20240104
PubMed Central ID:
PMC9867151
DOI:
10.3390/ijms24021430
PMID:
36674943
Czasopismo naukowe
HIV-1 maturation is the final step in the retroviral lifecycle that is regulated by the proteolytic cleavage of the Gag precursor protein. As a first-in-class HIV-1 maturation inhibitor (MI), bevirimat blocks virion maturation by disrupting capsid-spacer peptide 1 (CA-SP1) cleavage, which acts as the target of MIs. Previous alterations of beesioside I (1) produced (20S,24S)-15ꞵ,16ꞵ-diacetoxy-18,24; 20,24-diepoxy-9,19-cyclolanostane-3ꞵ,25-diol 3-O-3′,3′-dimethylsuccinate (3, DSC), showing similar anti-HIV potency compared to bevirimat. To ascertain the binding modes of this derivative, further modification of compound 1 was conducted. Three-dimensional quantitative structure−activity relationship (3D-QSAR) analysis combined with docking simulations and molecular dynamics (MD) were conducted. Five new derivatives were synthesized, among which compound 3b showed significant activity against HIV-1NL4-3 with an EC50 value of 0.28 µM. The developed 3D-QSAR model resulted in great predictive ability with training set (r2 = 0.99, q2 = 0.55). Molecular docking studies were complementary to the 3D-QSAR analysis, showing that DSC was differently bound to CA-SP1 with higher affinity than that of bevirimat. MD studies revealed that the complex of the ligand and the protein was stable, with root mean square deviation (RMSD) values <2.5 Å. The above results provided valuable insights into the potential of DSC as a prototype to develop new antiviral agents.
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