Bioactive phytoconstituents as potent inhibitors of casein kinase-2: dual implications in cancer and COVID-19 therapeutics. Issue 13 (10th March 2022)

• Record Type: Journal Article
• Authors: Anjum, Farah; Sulaimani, Md Nayab; Shafie, Alaa; Mohammad, Taj; Ashraf, Ghulam Md.; Bilgrami, Anwar L.; Alhumaydhi, Fahad A.; Alsagaby, Suliman A.; Yadav, Dharmendra Kumar; Hassan, Md. Imtaiyaz
• Is Part Of: RSC advances. Volume 12:Issue 13(2022)
• Page Start: 7872
• Page End: 7882
• Publication Date: 2022-03-10
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/d1ra09339h
• Languages: English
• ISSNs: 2046-2069

Abstract

Abstract : Showing protein–ligands interactions, electrostatic potential of CK2 bound to selected compounds, free energy landscapes of CK2-stylopine, and CK2-dehydroevodiamines complexes. Abstract : Casein kinase 2 (CK2) is a conserved serine/threonine-protein kinase involved in hematopoietic cell survival, cell cycle control, DNA repair, and other cellular processes. It plays a significant role in cancer progression and viral infection. CK2 is considered a potential drug target in cancers and COVID-19 therapy. In this study, we have performed a virtual screening of phytoconstituents from the IMPPAT database to identify some potential inhibitors of CK2. The initial filter was the physicochemical properties of the molecules following the Lipinski rule of five. Then binding affinity calculation, PAINS filter, ADMET, and PASS analyses followed by interaction analysis were carried out to discover nontoxic and better hits. Finally, two compounds, stylopine and dehydroevodiamines with appreciable affinity and specific interaction towards CK2, were identified. Their time-evolution analyses were carried out using all-atom molecular dynamics simulation, principal component analysis and free energy landscape. Altogether, we propose that stylopine and dehydroevodiamines can be further explored in in vitro and in vivo settings to develop anticancer and antiviral therapeutics.