Inflammatory cascades of the dysregulated inflammatory pathways in COVID-19 can cause excessive production of pro-inflammatory cytokines and chemokines leading to cytokine storm syndrome (CSS). The molecular cascades involved in the pathways may be targeted for discovery of new anti-inflammatory agents. Many plant extracts have been used clinically in the management of COVID-19, however, their immunosuppressive activities were mainly investigated based on in silico activity. Dietary flavonoids of the extracts such as quercetin, luteolin, kaempferol, naringenin, isorhamnetin, baicalein, wogonin, and rutin were commonly identified as responsible for their inhibitory effects. The present review critically analyzes the anti-inflammatory effects and mechanisms of phytochemicals, including dietary compounds against cytokine storm (CS) and hyperinflammation via inhibition of the altered inflammatory pathways triggered by SARS-CoV-2, published since the emergence of COVID-19 in December 2019. Only a few phytochemicals, mainly dietary compounds such as nanocurcumin, melatonin, quercetin, 6-shagoal, kaempferol, resveratrol, andrographolide, and colchicine have been investigated either in in silico or preliminary clinical studies to evaluate their anti-inflammatory effects against COVID-19. Sufficient pre-clinical studies on safety and efficacy of anti-inflammatory effects of the phytochemicals must be performed prior to proper clinical studies to develop them into therapeutic adjuvants in the prevention and treatmemt of COVID-19 symptoms.
Proteins of the DUF866 superfamily are exclusively found in eukaryotic cells. A member of the DUF866 superfamily, C1ORF123, is a human protein found in the open reading frame 123 of chromosome 1. The physiological role of C1ORF123 is yet to be determined. The only available protein structure of the DUF866 family shares just 26% sequence similarity and does not contain a zinc binding motif. Here, we present the crystal structure of the recombinant human C1ORF123 protein (rC1ORF123). The structure has a 2-fold internal symmetry dividing the monomeric protein into two mirrored halves that comprise of distinct electrostatic potential. The N-terminal half of rC1ORF123 includes a zinc-binding domain interacting with a zinc ion near to a potential ligand binding cavity. Functional studies of human C1ORF123 and its homologue in the fission yeast Schizosaccharomyces pombe (SpEss1) point to a role of DUF866 protein in mitochondrial oxidative phosphorylation.
Shrimp aquaculture contributes significantly to global economic growth, and the whiteleg shrimp, Penaeus vannamei, is a leading species in this industry. However, Vibrio parahaemolyticus infection poses a major challenge in ensuring the success of P. vannamei aquaculture. Despite its significance in this industry, the biological knowledge of its pathogenesis remains unclear. Hence, this study was conducted to identify the interaction sites and binding affinity between several immune-related proteins of P. vannamei with V. parahaemolyticus proteins associated with virulence factors. Potential interaction sites and the binding affinity between host and pathogen proteins were identified using molecular docking and dynamics (MD) simulation. The P. vannamei-V. parahaemolyticus protein-protein interaction of Complex 1 (Ferritin-HrpE/YscL family type III secretion apparatus protein), Complex 2 (Protein kinase domain-containing protein-Chemotaxis CheY protein), and Complex 3 (GPCR-Chemotaxis CheY protein) was found to interact with -4319.76, -5271.39, and -4725.57 of the docked score and the formation of intermolecular bonds at several interacting residues. The docked scores of Complex 1, Complex 2, and Complex 3 were validated using MD simulation analysis, which revealed these complexes greatly contribute to the interactions between P. vannamei and V. parahaemolyticus proteins, with binding free energies of -22.50 kJ/mol, -30.20 kJ/mol, and -26.27 kJ/mol, respectively. This finding illustrates the capability of computational approaches to search for molecular binding sites between host and pathogen, which could increase the knowledge of Vibrio spp. infection on shrimps, which then can be used to assist in the development of effective treatment.