PMID- 35658757
OWN - NLM
STAT- MEDLINE
DCOM- 20220608
LR  - 20230916
IS  - 1365-2060 (Electronic)
IS  - 0785-3890 (Print)
IS  - 0785-3890 (Linking)
VI  - 54
IP  - 1
DP  - 2022 Dec
TI  - Evaluation of a flavonoid library for inhibition of interaction of HIV-1 
      integrase with human LEDGF/p75 towards a structure-activity relationship.
PG  - 1590-1600
LID - 10.1080/07853890.2022.2081869 [doi]
AB  - Background: Proteinsprotein interaction (PPI) between lens epithelium-derived 
      growth factor (LEDGF/p75) and human immunodeficiency virus (HIV) integrase (IN) 
      becomes an attractive target for anti-HIV drug development.Methods: The blockade 
      of this interaction by small molecules could potentially inhibit HIV-1 
      replication. In this study, a panel of 99 structurally related flavonoids were 
      was tested, concerning their ability to inhibit IN-LEDGF/p75 interaction, using a 
      homogeneous time time-resolved fluorescence (HTRF) assay. Results: From the 
      obtained results, it was possible to observe that the flavonoid with hydroxyl 
      group in C3-, C4-, C5- and C7-position on the A-ring, C4'- and C5'-position of 
      the B-ring, a carbonyl group of the C-ring, was more active against IN-LEDGF/p75 
      interaction, through competitive inhibition. Moreover, the binding modes of 
      representative compounds, including myricetin, luteolin, dihydrorobinetin, 
      naringenin, epicatechin, genistein and helichrysetin, were analyzedanalysed by 
      molecular docking. Biolayer interferometry assay confirmed that these 
      representative compounds disrupted the PPI by binding to IN with KD values 
      ranging from 1.0 to 3.6 microM.Conclusion: This study presents the first to 
      quantitative comparation of the effect of flavonoids with different structural 
      subclasses on IN-LEDGF/p75 interaction. Our findings provide new insights into 
      the development of inhibitors targeting IN-LEDGF/p75 interaction using 
      flavonoids. Key MessagesHIV-1 integrase (IN)-LEDGF/p75 interaction is an 
      attractive target for antiviral drug development.For the first time, the 
      structure-activity relationship of flavonoids belonging to seven flavonoidic 
      subclasses on IN-LEDGF/p75 interaction was determined.This study comprehends an 
      HTRF-based screening system, biolayer interferometry and an in silico molecular 
      docking analysis.
FAU - Yin, Zhi-Hui
AU  - Yin ZH
AD  - First Hospital of Shanxi Medical University, Taiyuan, China.
FAU - Yan, Hao-Li
AU  - Yan HL
AD  - Center for Food and Drug Evaluation & Inspection of Henan, Zhengzhou, China.
FAU - Pan, Yu
AU  - Pan Y
AD  - School of Computer Engineering, Jiangsu University of Technology, Changzhou, 
      China.
FAU - Zhang, Da-Wei
AU  - Zhang DW
AUID- ORCID: 0000-0001-5938-2603
AD  - Institute of Bioinformatics and Medical Engineering, School of Electrical and 
      Information Engineering, Jiangsu University of Technology, Changzhou, China.
FAU - Yan, Xin
AU  - Yan X
AD  - First Hospital of Shanxi Medical University, Taiyuan, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Ann Med
JT  - Annals of medicine
JID - 8906388
RN  - 0 (Flavonoids)
RN  - 0 (HIV Integrase Inhibitors)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (lens epithelium-derived growth factor)
RN  - EC 2.7.7.- (HIV Integrase)
RN  - YY6481J2FF (p31 integrase protein, Human immunodeficiency virus 1)
SB  - IM
MH  - Flavonoids/pharmacology
MH  - *HIV Infections
MH  - *HIV Integrase/chemistry/metabolism
MH  - *HIV Integrase Inhibitors/chemistry/pharmacology
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins
MH  - Molecular Docking Simulation
MH  - Structure-Activity Relationship
PMC - PMC9176681
OTO - NOTNLM
OT  - Flavonoid
OT  - HIV-1
OT  - integrase
OT  - integrase-LEDGF interaction
COIS- The authors declare no competing interests.
EDAT- 2022/06/07 06:00
MHDA- 2022/06/09 06:00
PMCR- 2022/06/06
CRDT- 2022/06/06 09:51
PHST- 2022/06/06 09:51 [entrez]
PHST- 2022/06/07 06:00 [pubmed]
PHST- 2022/06/09 06:00 [medline]
PHST- 2022/06/06 00:00 [pmc-release]
AID - 2081869 [pii]
AID - 10.1080/07853890.2022.2081869 [doi]
PST - ppublish
SO  - Ann Med. 2022 Dec;54(1):1590-1600. doi: 10.1080/07853890.2022.2081869.