Description: The public health has declared an international state of emergency due to the spread of a new coronavirus (SARS-CoV-2) representing a real pandemic threat so that to find potential therapeutic agents is a dire need.
Since any traditional drug discovery program is a time-consuming and costly process requiring decades to be completed, in silico repurposing of existing drugs should be the preferred way for rapidly selecting compounds.
The aim of this recent research line is to develop a combined experimental-computational platform for repurposing drugs against different protein targets involved in SARS-CoV-2 infection.
In this context, we focused not only on some already characterized targets for SARS-CoV-2 i.e. the main protease (MPro) and the papain-like protease, but also on two further emerging targets in the Spike protein sequence besides ACE2 interaction site: a new type of ganglioside-binding domain (GBD), which seems to reside exactly in the galectin-like domain and a RGD sequence, generated by evolutionary mutation, recognized by the membrane receptor integrins.
Moreover, our idea is that ligands modulating the interaction with integrins or, at the same level, with a sugar through the galectin-domain, could represent a suitable therapeutic application.
These indications open a new scenario for the future COVID-19 treatment where a multi-targeting therapy could be applied considering ACE2, integrin and galectin domain inhibitors. To this aim bioinformatics, biochemical, biophysical and cellular methodologies will be used.
Figures:
Selected papers: Pirone L, Del Gatto A, Di Gaetano S, Saviano M, Capasso D, Zaccaro L, Pedone A Multi-Targeting Approach to Fight SARS-CoV-2 Attachment.E.Front Mol Biosci. 2020 Aug 3;7:186. doi: 10.3389/fmolb.2020.00186. eCollection 2020.
Fantini et al. Leveraging coronavirus binding to gangliosides for innovative vaccine and therapeutic strategies against COVID-19 B.B.R.C in press 2020
Delre P, Caporuscio F, Saviano M, Mangiatordi GF Repurposing Known Drugs as Covalent and Non-covalent Inhibitors of the SARS-CoV-2 Papain-Like Protease Front. Chem., 16 November 2020 | doi.org/10.3389/fchem.2020.594009
Petraglia F, Singh AA, Carafa V, Nebbioso A, Conte M, Scisciola L, Valente S, Baldi A, Mandoli A, Petrizzi VB, Ingenito C, De Falco S, Cicatiello V, Apicella I, Janssen-megens EM, Kim B, Yi G, Logie C, Heath S, Ruvo M, Wierenga ATJ, Flicek P, Yaspo ML, Della Valle V, Bernard O, Tomassi S, Novellino E, Feoli A, Sbardella G, Gut I, Vellenga E, Stunnenberg HG, Mai A, Martens JHA, Altucci L * Combined HAT/EZH2 modulation leads to cancer-selective cell death(350 views) Oncotarget (ISSN: 1949-2553electronic, 1949-2553linking), 2018 May 22; 9(39): 25630-25646. Impact Factor:5.008 ViewExport to BibTeXExport to EndNote
Kim YH, Shin SW, Pellicano R, Fagoonee S, Choi IJ, Kim YI, Park B, Choi JM, Kim SG, Choi J, Park JY, Oh S, Yang HJ, Lim JH, Im JP, Kim JS, Jung HC, Ponzetto A, Figura N, Malfertheiner P, Choi IJ, Kook MC, Kim YI, Cho SJ, Lee JY, Kim CG, Park B, Nam BH, Bae SE, Choi KD, Choe J, Kim SO, Na HK, Choi JY, Ahn JY, Jung KW, Lee J, Kim DH, Chang HS, Song HJ, Lee GH, Jung HY, Seta T, Takahashi Y, Noguchi Y, Shikata S, Sakai T, Sakai K, Yamashita Y, Nakayama T, Leja M, Park JY, Murillo R, Liepniece-karele I, Isajevs S, Kikuste I, Rudzite D, Krike P, Parshutin S, Polaka I, Kirsners A, Santare D, Folkmanis V, Daugule I, Plummer M, Herrero R, Tsukamoto T, Nakagawa M, Kiriyama Y, Toyoda T, Cao X, Corral JE, Mera R, Dye CW, Morgan DR, Lee YC, Lin JT, Garcia Martin R, Matia Cubillo A, Lee SH, Park JM, Han YM, Ko WJ, Hahm KB, Leontiadis GI, Ford AC, Ichinose M, Sugano K, Jeong M, Park JM, Han YM, Park KY, Lee DH, Yoo JH, Cho JY, Hahm KB, Bang CS, Baik GH, Shin IS, Kim JB, Suk KT, Yoon JH, Kim YS, Kim DJ * Helicobacter pylori Eradication for Prevention of Metachronous Recurrence after Endoscopic Resection of Early Gastric Cancer(414 views) N Engl J Med (ISSN: 0028-4793, 0028-4793linking, 1533-4406electronic), 2015 Jun; 30642104201566393291: 749-756. Impact Factor:59.558 ViewExport to BibTeXExport to EndNote