PMID- 36574379
OWN - NLM
STAT- MEDLINE
DCOM- 20221230
LR  - 20230109
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 17
IP  - 12
DP  - 2022
TI  - Carotenoids as potential inhibitors of TNFalpha in COVID-19 treatment.
PG  - e0276538
LID - 10.1371/journal.pone.0276538 [doi]
LID - e0276538
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a multifunctional pro-inflammatory 
      cytokine, responsible for autoimmune and inflammatory disorders. In COVID-19 
      patients, increased TNF-alpha concentration may provoke inflammatory cascade and 
      induce the initiation of cytokine storm that may result in fatal pneumonia and 
      acute respiratory distress syndrome (ADRS). Hence, TNFalpha is assumed to be a 
      promising drug target against cytokine storm in COVID-19 patients. In the present 
      study, we focused on finding novel small molecules that can directly block 
      TNF-alpha-hTNFR1 (human TNF receptor 1) interaction. In this regards, 
      TNF-alpha-inhibiting capacity of natural carotenoids was investigated in terms of 
      blocking TNF-alpha-hTNFR1 interaction in COVID-19 patients with the help of a 
      combination of in silico approaches, based on virtual screening, molecular 
      docking, and molecular dynamics (MD) simulation. A total of 125 carotenoids were 
      selected out of 1204 natural molecules, based on their pharmacokinetics 
      properties and they all met Lipinski's rule of five. Among them, Sorgomol, 
      Strigol and Orobanchol had the most favorable DeltaG with the best ADME (absorption, 
      distribution, metabolism, excretion) properties, and were selected for MD 
      simulation studies, which explored the complex stability and the impact of 
      ligands on protein conformation. Our results showed that Sorgomol formed the most 
      hydrogen bonds, resulting in the highest binding energy with lowest RMSD and 
      RMSF, which made it the most appropriate candidate as TNF-alpha inhibitor. In 
      conclusion, the present study could serve to expand possibilities to develop new 
      therapeutic small molecules against TNF-alpha.
CI  - Copyright: (c) 2022 Taghipour et al. This is an open access article distributed 
      under the terms of the Creative Commons Attribution License, which permits 
      unrestricted use, distribution, and reproduction in any medium, provided the 
      original author and source are credited.
FAU - Taghipour, Farzaneh
AU  - Taghipour F
AD  - Department of Cellular and Molecular Biology, School of Biology, College of 
      Science, University of Tehran, Tehran, Iran.
FAU - Motamed, Nasrin
AU  - Motamed N
AUID- ORCID: 0000-0002-6892-423X
AD  - Department of Cellular and Molecular Biology, School of Biology, College of 
      Science, University of Tehran, Tehran, Iran.
FAU - Amoozegar, Mohammad Ali
AU  - Amoozegar MA
AD  - Department of Microbiology, School of Biology, College of Science, University of 
      Tehran, Tehran, Iran.
FAU - Shahhoseini, Maryam
AU  - Shahhoseini M
AD  - Department of Cellular and Molecular Biology, School of Biology, College of 
      Science, University of Tehran, Tehran, Iran.
AD  - Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute 
      for Reproductive Biomedicine, ACECR, Tehran, Iran.
AD  - Reproductive Epidemiology Research Center, Royan Institute for Reproductive 
      Biomedicine, ACECR, Tehran, Iran.
FAU - Mahdian, Soodeh
AU  - Mahdian S
AD  - Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute 
      for Reproductive Biomedicine, ACECR, Tehran, Iran.
AD  - Department of Cellular and Molecular Biology, Faculty of Biological Sciences, 
      North Tehran Branch, Islamic Azad University, Tehran, Iran.
LA  - eng
PT  - Journal Article
DEP - 20221227
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (sorgomol)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 36-88-4 (Carotenoids)
SB  - IM
MH  - Humans
MH  - *COVID-19
MH  - COVID-19 Drug Treatment
MH  - Cytokine Release Syndrome
MH  - Molecular Docking Simulation
MH  - Molecular Dynamics Simulation
MH  - *Tumor Necrosis Factor-alpha/antagonists & inhibitors
MH  - *Carotenoids/pharmacology
PMC - PMC9794061
COIS- The authors have declared that no competing interests exist.
EDAT- 2022/12/28 06:00
MHDA- 2022/12/30 06:00
PMCR- 2022/12/27
CRDT- 2022/12/27 13:33
PHST- 2022/02/13 00:00 [received]
PHST- 2022/10/08 00:00 [accepted]
PHST- 2022/12/27 13:33 [entrez]
PHST- 2022/12/28 06:00 [pubmed]
PHST- 2022/12/30 06:00 [medline]
PHST- 2022/12/27 00:00 [pmc-release]
AID - PONE-D-22-04402 [pii]
AID - 10.1371/journal.pone.0276538 [doi]
PST - epublish
SO  - PLoS One. 2022 Dec 27;17(12):e0276538. doi: 10.1371/journal.pone.0276538. 
      eCollection 2022.