PMID- 30886338
OWN - NLM
STAT- MEDLINE
DCOM- 20201014
LR  - 20231006
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 9
IP  - 1
DP  - 2019 Mar 18
TI  - Anti-HIV-1 integrase potency of methylgallate from Alchornea cordifolia using in 
      vitro and in silico approaches.
PG  - 4718
LID - 10.1038/s41598-019-41403-x [doi]
LID - 4718
AB  - According to the 2018 report of the United Nations Programme on HIV/AIDS 
      (UNAIDS), acquired immune deficiency syndrome (AIDS), a disease caused by the 
      human immunodeficiency virus (HIV), remains a significant public health problem. 
      The non-existence of a cure or effective vaccine for the disease and the 
      associated emergence of resistant viral strains imply an urgent need for the 
      discovery of novel anti-HIV drug candidates. The current study aimed to identify 
      potential anti-retroviral compounds from Alchornea cordifolia. Bioactive 
      compounds were identified using several chromatographic and spectroscopic 
      techniques and subsequently evaluated for cytotoxicity and anti-HIV properties. 
      Molecular modelling studies against HIV-1 integrase (HIV-1 IN) were performed to 
      decipher the mode of action of methylgallate, the most potent compound 
      (IC(50) = 3.7 nM) and its analogues from ZINC database. Cytotoxicity assays 
      showed that neither the isolated compounds nor the crude methanolic extract 
      displayed cytotoxicity effects on the HeLa cell line. A strong correlation 
      between the in vitro and in silico results was observed and important HIV-1 IN 
      residues interacting with the different compounds were identified. These current 
      results indicate that methylgallate is the main anti-HIV-1 compound in A. 
      cordifolia stem bark, and could be a potential platform for the development of 
      new HIV-1 IN inhibitors.
FAU - Siwe-Noundou, Xavier
AU  - Siwe-Noundou X
AUID- ORCID: 0000-0002-8667-8351
AD  - Department of Chemistry, Rhodes University, Grahamstown, 6140, South Africa. 
      xavsiw@gmail.com.
AD  - Department of Biochemistry and Microbiology, Rhodes University, Grahamstown, 
      6140, South Africa. xavsiw@gmail.com.
FAU - Musyoka, Thommas M
AU  - Musyoka TM
AD  - Research Unit in Bioinformatics (RUBi), Department of Biochemistry and 
      Microbiology, Rhodes University, Grahamstown, 6140, South Africa.
FAU - Moses, Vuyani
AU  - Moses V
AD  - Research Unit in Bioinformatics (RUBi), Department of Biochemistry and 
      Microbiology, Rhodes University, Grahamstown, 6140, South Africa.
FAU - Ndinteh, Derek T
AU  - Ndinteh DT
AD  - Department of Applied Chemistry, University of Johannesburg, Doornfontein, 
      Johannesburg, 2028, South Africa.
FAU - Mnkandhla, Dumisani
AU  - Mnkandhla D
AD  - Department of Biochemistry and Microbiology, Rhodes University, Grahamstown, 
      6140, South Africa.
FAU - Hoppe, Heinrich
AU  - Hoppe H
AD  - Department of Biochemistry and Microbiology, Rhodes University, Grahamstown, 
      6140, South Africa.
FAU - Tastan Bishop, Ozlem
AU  - Tastan Bishop O
AUID- ORCID: 0000-0001-6861-7849
AD  - Research Unit in Bioinformatics (RUBi), Department of Biochemistry and 
      Microbiology, Rhodes University, Grahamstown, 6140, South Africa. 
      O.TastanBishop@ru.ac.za.
FAU - Krause, Rui W M
AU  - Krause RWM
AD  - Department of Chemistry, Rhodes University, Grahamstown, 6140, South Africa. 
      r.krause@ru.ac.za.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190318
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (HIV Integrase Inhibitors)
RN  - 0 (Recombinant Proteins)
RN  - 623D3XG80C (methyl gallate)
RN  - 632XD903SP (Gallic Acid)
RN  - EC 2.7.7.- (HIV Integrase)
RN  - YY6481J2FF (p31 integrase protein, Human immunodeficiency virus 1)
SB  - IM
MH  - Acquired Immunodeficiency Syndrome/*drug therapy/virology
MH  - Drug Evaluation, Preclinical
MH  - Euphorbiaceae/*chemistry
MH  - Gallic Acid/*analogs & derivatives/chemistry/isolation & 
      purification/pharmacology/therapeutic use
MH  - HIV Integrase/*metabolism/ultrastructure
MH  - HIV Integrase Inhibitors/chemistry/isolation & 
      purification/*pharmacology/therapeutic use
MH  - HIV-1/drug effects/enzymology
MH  - HeLa Cells
MH  - Humans
MH  - Inhibitory Concentration 50
MH  - Molecular Docking Simulation
MH  - Molecular Dynamics Simulation
MH  - Plant Bark/chemistry
MH  - Plant Stems/chemistry
MH  - Protein Domains
MH  - Recombinant Proteins
MH  - Toxicity Tests
PMC - PMC6423119
COIS- The authors declare no competing interests.
EDAT- 2019/03/20 06:00
MHDA- 2020/10/21 06:00
PMCR- 2019/03/18
CRDT- 2019/03/20 06:00
PHST- 2018/10/16 00:00 [received]
PHST- 2019/03/05 00:00 [accepted]
PHST- 2019/03/20 06:00 [entrez]
PHST- 2019/03/20 06:00 [pubmed]
PHST- 2020/10/21 06:00 [medline]
PHST- 2019/03/18 00:00 [pmc-release]
AID - 10.1038/s41598-019-41403-x [pii]
AID - 41403 [pii]
AID - 10.1038/s41598-019-41403-x [doi]
PST - epublish
SO  - Sci Rep. 2019 Mar 18;9(1):4718. doi: 10.1038/s41598-019-41403-x.