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. 2022 Dec 27;17(12):e0276538.
doi: 10.1371/journal.pone.0276538. eCollection 2022.

Carotenoids as potential inhibitors of TNFα in COVID-19 treatment

Farzaneh Taghipour  1 , Nasrin Motamed  1 , Mohammad Ali Amoozegar  2 , Maryam Shahhoseini  1   3   4 , Soodeh Mahdian  3   5
Affiliations

Carotenoids as potential inhibitors of TNFα in COVID-19 treatment

Farzaneh Taghipour et al. PLoS One. .

Abstract

Tumor necrosis factor-alpha (TNF-α) is a multifunctional pro-inflammatory cytokine, responsible for autoimmune and inflammatory disorders. In COVID-19 patients, increased TNF-α 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, TNFα 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-α-hTNFR1 (human TNF receptor 1) interaction. In this regards, TNF-α-inhibiting capacity of natural carotenoids was investigated in terms of blocking TNF-α-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 ΔG 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-α inhibitor. In conclusion, the present study could serve to expand possibilities to develop new therapeutic small molecules against TNF-α.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. mTNFα-hTNFR1 interaction with Orobanchol.
a. 3D shape of mTNFα-hTNFR1 interaction with Orobanchol. b. Illustration of hydrophobic bond formation between Orobanchol and the mTNFα-hTNFR1 complex. Orobanchol forms 2 hydrogen bonds with LYS112 of mTNFα.
Fig 2
Fig 2. mTNFα-hTNFR1 interaction with Strigol.
a.3D shape of mTNFα-hTNFR1 interaction with Strigol. b. Illustration of hydrophobic bond formation between Strigol and the mTNFα-hTNFR1 complex. Strigol forms 3 hydrogen bonds with ASN116, ASN134, and TYR103, and 1 π-sigma bond with PHE115 of hTNFR1.
Fig 3
Fig 3. mTNFα-hTNFR1 interaction with Sorgomol.
a.3D shape of mTNFα-hTNFR1 interaction with Sorgomol. b. Illustration of hydrophobic bond formation between Sorgomol with the mTNFα-hTNFR1 complex. Sorgomol forms 3 hydrogen bonds with GLN102, ASN116, and TYR103, and 1 π-sigma bond with PHE115 of hTNFR1. It also forms 1 hydrogen bond with GLN68, and 1 π-sigma bond with PRO113 of mTNFα.
Fig 4
Fig 4. Root mean square deviation (RMSD) of c-alpha for the protein in interaction with Sorgomol, Orobanchol and Strigol during 100 ns simulation.
Fig 5
Fig 5. Root mean square fluctuation (RMSF) of c-alpha for the protein in interaction with Sorgomol, Orobanchol and Strigol during 100 ns simulation.
See this image and copyright information in PMC

References

    1. Duret P-M, Sebbag E, Mallick A, Gravier S, Spielmann L, Messer L. Recovery from COVID-19 in a patient with spondyloarthritis treated with TNF-alpha inhibitor etanercept. Annals of the rheumatic diseases. 2020;79(9):1251–2. doi: 10.1136/annrheumdis-2020-217362 - DOI - PMC - PubMed
    1. Henderson LA, Canna SW, Schulert GS, Volpi S, Lee PY, Kernan KF, et al.. On the alert for cytokine storm: immunopathology in COVID‐19. Arthritis & Rheumatology. 2020;72(7):1059–63. doi: 10.1002/art.41285 - DOI - PMC - PubMed
    1. Jamilloux Y, Henry T, Belot A, Viel S, Fauter M, El Jammal T, et al.. Should we stimulate or suppress immune responses in COVID-19? Cytokine and anti-cytokine interventions. Autoimmunity reviews. 2020:102567. doi: 10.1016/j.autrev.2020.102567 - DOI - PMC - PubMed
    1. Robinson PC, Liew DF, Liew JW, Monaco C, Richards D, Shivakumar S, et al.. The Potential for Repurposing Anti-TNF as a Therapy for the Treatment of COVID-19. Med. 2020. doi: 10.1016/j.medj.2020.11.005 - DOI - PMC - PubMed
    1. Feldmann M, Maini RN, Woody JN, Holgate ST, Winter G, Rowland M, et al.. Trials of anti-tumour necrosis factor therapy for COVID-19 are urgently needed. The Lancet. 2020;395(10234):1407–9. doi: 10.1016/S0140-6736(20)30858-8 - DOI - PMC - PubMed

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