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<\/figure>PC27 – Maria Rosaria Paravati<\/strong><\/p>\n\n\n\n University Magna Graecia of Catanzaro, Italy<\/p>\n\n\n\n LinkedIn<\/a><\/strong> –<\/strong> ORCID<\/a><\/strong> <\/p>\n","protected":false},"excerpt":{"rendered":" PC27 – Maria Rosaria Paravati University Magna Graecia of Catanzaro, Italy LinkedIn – ORCIDmrparavati@unicz.it From Viral Proteins to Host Targets: Unveiling Casein Kinase 2 as the Antiviral Mechanism of the [4,7]-Phenanthroline Scaffold Paravati Maria Rosaria1, Romeo […]<\/p>\n","protected":false},"author":10371,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1],"tags":[],"class_list":["post-2174","post","type-post","status-publish","format-standard","hentry","category-senza-categoria"],"_links":{"self":[{"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/posts\/2174","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/users\/10371"}],"replies":[{"embeddable":true,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/comments?post=2174"}],"version-history":[{"count":4,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/posts\/2174\/revisions"}],"predecessor-version":[{"id":2454,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/posts\/2174\/revisions\/2454"}],"wp:attachment":[{"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/media?parent=2174"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/categories?post=2174"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/tags?post=2174"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}
mrparavati@unicz.it<\/strong><\/p>\n<\/div><\/div>\n\n\n\nFrom Viral Proteins to Host Targets: Unveiling Casein Kinase 2 as the Antiviral Mechanism of the [4,7]-Phenanthroline Scaffold<\/strong><\/strong><\/td><\/tr> Paravati Maria Rosaria1<\/sup>, Romeo Isabella 1<\/sup>, Carta Antonio 2<\/sup>, Deiana Andrea 2<\/sup>, Murineddu Gabriele 2<\/sup> and Alcaro Stefano 1<\/sup><\/em>
1<\/sup><\/em> Dipartimento di Scienze della Salute, Universit\u00e0 \u201cMagna Gr\u00e6cia\u201d di Catanzaro, Campus \u201cS. Venuta\u201d, Viale Europa, 88100 Catanzaro, Italy
2<\/sup><\/em> Department of Medicine, Surgery and Pharmacy, University of Sassari, Via Muroni 23a, Sassari, Italy<\/td><\/tr>Abstract<\/strong>
The [4,7]-phenanthroline compound PS1100 exhibits broad-spectrum activity against several viruses, including SARS-CoV-2 and Zika, making it a compelling scaffold for pan-viral drug discovery [1]. Initially, a computational target fishing study was performed on the key non-structural proteins (NSPs) of SARS-CoV-2 (NSP3, 5, 12, 13, 14, 15, and 16) [2]. However, molecular docking and Molecular Mechanics Generalized Born Surface Area (MM\/GBSA) analyses indicated poor affinity for these viral enzymes, a finding corroborated by in vivo<\/em> assays showing no direct antiviral enzymatic inhibition [3]. This negative outcome prompted a shift toward host-directed therapy, hypothesizing that PS1100 targets cellular factors exploited by viruses, such as Casein Kinase 2 (CK2) [4]. CK2 is a ubiquitous Ser\/Thr kinase essential for the replication of numerous viruses. It exists as a heterotetramer with two catalytic (\u03b1 or \u03b1\u2019) and two regulatory (\u03b2) subunits, featuring a conserved ATP-binding site and a specific \u03b1D pocket [5]. Given its structural similarity to silmitasertib, we investigated PS1100 as a CK2 inhibitor. Our in silico<\/em> studies showed binding affinities comparable or superior to silmitasertib for the \u03b1 and \u03b1\u2019 subunits, respectively [3]. Thermal Shift Assay (TSA) demonstrated a modest binding affinity, while X-ray crystallography definitively confirmed that PS1100 occupies the CK2 binding pocket. Subsequently, building on these results, a library of 1,945 phenanthroline derivatives was designed, identifying four lead candidates currently under in vitro<\/em> evaluation. These were used to develop a second library of 266 bivalent molecules, designed to simultaneously target the ATP site and the \u03b1D pocket via 5-8 carbon alkyl linkers, inspired by the inhibitor KN2. Ongoing in silico<\/em> studies are evaluating their binding modes, supporting PS1100 derivatives as promising agents for host-directed, broad-spectrum antiviral strategies.<\/td><\/tr>References <\/strong>
[1] Carta, A.; Loriga, M.; Paglietti, G.; Ferrone, M.; Fermeglia, M.; Pricl, S.; Sanna, T.; Ibba, C.; La Colla, P.; Loddo, R. Design, synthesis, and preliminary in vitro and in silico antiviral activity of [4,7]phenantrolines and 1-oxo-1,4-dihydro-[4,7]phenantrolines against single-stranded positive-sense RNA genome viruses. Bioorg Med Chem.<\/em> 2007<\/strong>, 15<\/em>:1914-27.
[2] Kim, D.; Lee, J.Y.; Yang, J.S.; Kim, J.W.; Kim, V.N.; Chang, H. The Architecture of SARS-CoV-2 Transcriptome. Cell.<\/em> 2020<\/strong>, 181<\/em>:914-921
[3] Schr\u00f6dinger, LLC, New York, NY, 2018<\/strong>.
[4] Quezada Meza, C.P.; Ruzzene, M. Protein Kinase CK2 and SARS-CoV-2: An Expected Interplay Story. Kinases and Phosphatases<\/em>. 2023<\/strong>, 1<\/em>:141-150.
[5] Zonta, F.; Borgo, C.; Quezada Meza, C.P.; Masgras, I.; Rasola, A.; Salvi, M.; Pinna, L.A.; Ruzzene M. Contribution of the CK2 Catalytic Isoforms \u03b1 and \u03b1’ to the Glycolytic Phenotype of Tumor Cells. Cells<\/em>. 2021<\/strong>, 10<\/em>:181.<\/td><\/tr><\/tbody><\/table><\/div><\/figure>\n\n\n\n