scholarly journals Potential Role of Colchicine in Combating COVID-19 Cytokine Storm and Its Ability to Inhibit Protease Enzyme of SARS-CoV-2 as Conferred by Molecular Docking Analysis

Medicina ◽  
2021 ◽  
Vol 58 (1) ◽  
pp. 20
Author(s):  
Noha A. Kamel ◽  
Nasser S. M. Ismail ◽  
Ibrahim S. Yahia ◽  
Khaled M. Aboshanab
Keyword(s):  
Molecular Docking ◽  
Hydrophobic Interactions ◽  
Cytokine Storm ◽  
Destructive Effect ◽  
Health Crisis ◽  
Docking Analysis ◽  
Global Pandemic ◽  
Protease Enzyme ◽  
Anti Inflammatory ◽  
Molecular Docking Analysis

Despite the advance in the management of Coronavirus disease 2019 (COVID-19), the global pandemic is still ongoing with a massive health crisis. COVID-19 manifestations may range from mild symptoms to severe life threatening ones. The hallmark of the disease severity is related to the overproduction of pro-inflammatory cytokines manifested as a cytokine storm. Based on its anti-inflammatory activity through interfering with several pro and anti-inflammatory pathways, colchicine had been proposed to reduce the cytokine storm and subsequently improve clinical outcomes. Molecular docking analysis of colchicine against RNA-dependent RNA polymerase (RdRp) and protease enzymes of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) revealed that colchicine provided a grid-based molecular docking method, C-DOCKER interaction energy 64.26 and 47.53 (Kcal/mol) with protease and RdRp, respectively. This finding indicated higher binding stability for colchicine–protease complexes than the colchicine–RdRp complex with the involvement of seven hydrogen bonds, six hydrogen acceptors with Asn142, Gly143, Ser144, and Glu166 and one hydrogen-bond donors with Cys145 of the protease enzyme. This is in addition to three hydrophobic interactions with His172, Glu166, and Arg188. A good alignment with the reference compound, Boceprevir, indicated high probability of binding to the protease enzyme of SARS-CoV-2. In conclusion, colchicine can ameliorate the destructive effect of the COVID-19 cytokine storm with a strong evidence of antiviral activity by inhibiting the protease enzyme of SARS-CoV-2.

scholarly journals Discovery of 2-Substituted 3-Arylquinoline Derivatives as Potential Anti-Inflammatory Agents Through Inhibition of LPS-Induced Inflammatory Responses in Macrophages

Molecules ◽  
2019 ◽  
Vol 24 (6) ◽  
pp. 1162 ◽  
Author(s):  
Cheng-Yao Yang ◽  
Yung-Li Hung ◽  
Kai-Wei Tang ◽  
Shu-Chi Wang ◽  
Chih-Hua Tseng ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Inflammatory Cytokines ◽  
Inflammatory Responses ◽  
Hydrophobic Interactions ◽  
Activated Macrophages ◽  
Docking Analysis ◽  
Lead Compounds ◽  
Anti Inflammatory ◽  
Molecular Docking Analysis ◽  
Pro Inflammatory Cytokines

We describe herein the preparation of certain 2-substituted 3-arylquinoline derivatives and the evaluation of their anti-inflammatory effects in LPS-activated murine J774A.1 macrophage cells. Among these newly synthesized 2-substituted 3-arylquinoline derivatives, 2-(4-methoxy- benzoyl)-3-(3,4,5-trimethoxyphenyl)quinoline (18a) and 2-(4-fluorobenzoyl)-3-(3,4,5-trimethoxy- phenyl)quinoline (18b) are two of the most active compounds which can inhibit the production of NO at non-cytotoxic concentrations. Our results have also indicated that compounds 18a and 18b significantly decrease the secretion of pro-inflammatory cytokines (TNF-á and IL-6), inhibit the expression of iNOS, suppress the phosphorylation of MAPKs, and attenuate the activity of NF-êB by LPS-activated macrophages. Through molecular docking analysis, we found that 18b could fit into the middle of the TNF-á dimer and form hydrophobic interactions with Leu55, Leu57 chain A and B, Tyr59, Val123 chain B and D, Ile 155. These results suggest that both 18a and 18b are potential lead compounds in inhibiting LPS-induced inflammatory responses. Further structural optimization to discover novel anti-inflammatory agents is ongoing.

scholarly journals Conserved in 186 countries the RBD fraction of SARS CoV-2 S-protein with in-silicoT500S mutation strongly blocks ACE2 rejecting the viral spike; A Molecular-docking analysis.

2021 ◽  
Author(s):  
Amrita Banerjee ◽  
Mehak Kanwar ◽  
Dipannita Santra ◽  
Smarajit Maiti
Keyword(s):  
Crystal Structure ◽  
Molecular Docking ◽  
Receptor Binding ◽  
Structural Alignment ◽  
Receptor Binding Domain ◽  
Wild Type ◽  
Docking Analysis ◽  
Global Pandemic ◽  
Complete Rejection ◽  
Molecular Docking Analysis

SARS-CoV-2 developed global-pandemic with millions of infections/deaths. Blocker/inhibitor of ACE2 and viral-spikes Receptor-Binding-Domain RBD-blockers are helpful. Here, conserved RBD (CUTs) from 186-countries were compared with WUHAN-Hu-1 wild-type by CLUSTAL-X2 and Structural-alignment using Pymol. The RBD of ACE2-bound nCOV2 crystal-structure (2.68)6VW1 was analyzed by Haddock-PatchDock. Extensive structural study/trial to introduce point/double/triple mutations in the following locations (Y489S/Y453S/T500S/T500Y)/(Y489S,Y453S/Y489S,T500S/Y489S,T500Y/Y453S,T500S/Y453S,T500Y)/ (Y489S,Y453S,T500S/Y489S,Y453S,T500Y) of CUT4 (most-effective) were tested with Swiss-Model-Expacy. Blind-docking of mutated-CUTs to ACE2 (6VW1) by Haddock-Hawkdock was performed and optimally complete-rejection of nCOV2 to ACE2 was noticed. Further, competitive-docking/binding-analyses were done by PRODIGY. Present results suggest that compared to the wild-spike, CUT4 showed extra LYS31-PHE490/GLN42-GLN498 bonding and lack of TYR41-THR500 interaction (in wild H-bond:2.639) with ACE2 RBD. Mutated-CUT4 strongly binds with the ACE2-RBD, promoting TYR41-T500S (H-bond: 2.0 and 1.8)/T500Y (H-bond:2.6) interaction and complete inhibition of ACE2 RBD-nCOV2. Mutant combinations T500S,Y489S,T500S and Y489S,Y453S,T500Y mostly blocked ACE2. Conclusively, CUT4-mutant rejects whole glycosylated-nCoV2 pre-dock/post-dock/competitive-docking conditions.

scholarly journals Molecular docking analysis and evaluation of the antibacterial and antioxidant activities of the constituents of Ocimum cufodontii

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Muhdin Aliye ◽  
Aman Dekebo ◽  
Hailemichael Tesso ◽  
Teshome Abdo ◽  
Rajalakshmanan Eswaramoorthy ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Essential Oil ◽  
Hydrophobic Interactions ◽  
Antioxidant Activities ◽  
Reducing Power ◽  
Principal Component ◽  
Inhibition Zone ◽  
Hexane Extract ◽  
Docking Analysis ◽  
Molecular Docking Analysis

AbstractOcimum cufodontii ((Lanza) A.J.Paton) has been traditionally used in Ethiopia against bacteria. The extracts of the leaves and roots of O. cufodontii after silica gel column chromatography furnished compounds 1–5, compounds 3 and 4 are new natural products. The oil from the hydro-distillation of the leaves, after analyzed with GC–MS, has led to the identification of β-caryophyllene as a principal component, suggesting the essential oil as medicine and spices to enhance the taste of food. The constituents of O. cufodontii were assessed for their antibacterial activity against E. coli, K. pneumonia, S. typhymurium and S. aureus. The best activity was displayed against S. aureus by the hexane extract of the roots, compound 4, and the essential oil with an inhibition zone of 17, 15, and 19 mm, respectively. Molecular docking analysis revealed that compound 1 has better docking efficiency and forms hydrophobic interactions with five amino acids (ARG192, PHE196, GLU185, GLU193, and LYS189). This suggests that the compounds may act as potential inhibitors of DNA gyrase. The constituents were also assessed for their antioxidant activities using DPPH, ferric thicyanate and ferric reducing power assay. The hexane extracts of the roots inhibited the DPPH radical and peroxide formation by 90.5 and 83%, respectively, suggesting the potential of the extract as an antioxidant. Furthermore, the hexane extract of the roots of O. cufodontii exhibited the maximum reducing power compared with the EtOAc and methanol extracts. Hence, the activity displayed herein indicated as the plant has great potential as a remedy for diseases caused by bacteria and radicals.

scholarly journals Molecular docking analysis of furfural and isoginkgetin with heme oxygenase I and PPARγ

2021 ◽  
Vol 17 (2) ◽  
pp. 356-362
Author(s):  
Preetha Santhakumar ◽  
Keyword(s):  
Molecular Docking ◽  
Cascade Process ◽  
Docking Analysis ◽  
Target Proteins ◽  
Hydrogen Bond Interactions ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Necrosis Factor ◽  
Molecular Docking Analysis

Inflammatory is cascade process triggered by pro-inflammatory cytokines and anti-inflammatory. In the present study anti-inflammatory activity of Stachydrine and Sakuranetin were studied against the inflammatory target proteins IL-6 and TNF-α by using molecular docking analysis. Both compounds showed the good binding with selected target proteins. Compared to Sakuranetin, the Stachydrine have lowest binding energy and good hydrogen bond interactions. Hence results of study indicated that Stachydrine possessed high and specific inhibitory activity on tumor necrosis factor-α and interleukin-6.

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