ABSTRACT
One of the most common causes of mortality in COVID-19 patients is cytokine release syndrome (CRS). Though several cytokines are involved in CRS, the role of Interleukin 6 is significant. Considering the importance of IL-6 inhibition and the drawbacks of the existing monoclonal antibodies, the present study develops new flavonoid metal complexes as immune boosters targeting IL-6 for SARS-CoV-2 treatment. To identify the potential flavonoids from 152 secondary plant metabolites, PyRx 0.9 tool has been used. The top scorer quercetin was converted into quercetin-oxime. Seven metal complexes (QM-1 to QM-7) were made from quercetin-oxime by utilizing divalent metals such as zinc, copper, magnesium, cobalt, barium, and cadmium. It was assumed that all compounds were moderately soluble and would not penetrate the BBB through in silico ADME studies. However, the in vitro heamolytic research revealed a modest heamolytic effect in all seven complexes. To know the IL-6 inhibitory potential preliminary level, the complexes were screened for cytotoxicity in cell lines MCF-7 which predominantly expresses the IL-6 level. The cytotoxic effects of all complexes were considerable relative to the marketable Nutridac formulation. The complexes quercetin-Zinc (QM1) and quercetin-Zinc-Ascorbic acid (QM7) showed significant cytotoxicity on MCF-7 compared to Nutridac and no cytotoxic toward the normal cell lines. © 2022, National Institute of Science Communication and Policy Research. All rights reserved.
ABSTRACT
It is observed that cytokine release syndrome (CRS) is one of the major causes of the death of several COVID-19 patients. Though several cytokines are involved in CRS, IL-6 modulation plays a major role. We aim to develop new flavonoid metal complexes as immune boosters targeting IL-6 for SARS-CoV-2 treatment. To find potential flavonoids, PyRx 0.9 tool has been used to dock 152 secondary plant metabolites against IL-6 (PDB ID: 1ALU). The top scorer flavonoid (quercetin) was made into quercetin zinc ascorbic acid metal complex (QM-1). The in-vitro hemolytic research revealed a modest hemolytic effect in the QM1 metal complex. To control the IL-6 inhibitory potential, the QM1 complex was screened for cytotoxicity in cell lines MCF-7 which predominantly expresses the IL-6 level. The cytotoxic effects of the QM1 complex were considered relative to the marketable Nutridac formulation. The complex quercetin-Zinc-Ascorbic acid (QM1) significantly affected MCF-7 cells in concentrations 48.54 μg/mL, respectively. © The Electrochemical Society