Meet-EU 2023

“Meet-EU” is an international team-based course organised by five 4EU+ member universities (Heidelberg, Milan, Paris, Prague, Warsaw) as part of the 4EU+ joint educational offer during the academic year 2023/2021. Meet-EU has been designed to promote interdisciplinary training through research and welcomes students from different disciplines, from computer science, physics and mathematics to chemistry, biology and biotechnologies.

Students are asked to address and solve a specific research problem under the supervision of tutors at each university. Students organize themselves in small groups of 4-5 students each. Each group works independently to propose a solution to the question.

At mid-course, a face-to-face meeting will be held, the activities completed by each group will be discussed and the groups will be paired to implement a joint second step of the project. Paired teams should be preferably belong to different countries.

At a final meeting, each group will present its results, which will be evaluated by a panel of experts in the field.

The official language of the course is English.

The course is based on team work and each team will conduct independent research activities delivering a presentation. Essays will be presented at a face-to-face conference in February 2024 in Prague. ECTS recognition is done at the home university and faculty.

This year’s topic is the same as the last year. The focus is on structural bioinformatics and involves docking simulations and virtual screening campaigns on the Sars-Cov-2 helicase protein (Nsp-13). Each group will develop an original computational procedure for the identification of potential Nsp-13 inhibitors. Starting from a set of resolved enzyme structures, the project will include refinement of the protein structures, analysis of their binding sites, selection of the most suitable pockets, preliminary docking studies by using known inhibitors, developing of predictive models to be applied in the following virtual screening campaigns. Hence, the project will involve computational techniques such as molecular dynamics and docking simulations as well as pocket searching and structural analysis. These techniques could be combined with artificial intelligence algorithms to enhance the predictive power of the performed simulations.

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• Raubenolt BA, Islam NN, Summa CM, Rick SW. Molecular dynamics simulations of the flexibility and inhibition of SARS-CoV-2 NSP 13 helicase. J Mol Graph Model. 2022;112:108122. doi:10.1016/j.jmgm.2022.108122
• Tolbatov I, Storchi L, Marrone A. Structural Reshaping of the Zinc-Finger Domain of the SARS-CoV-2 nsp13 Protein Using Bismuth(III) Ions: A Multilevel Computational Study. Inorg Chem. 2022;61(39):15664-15677. doi:10.1021/acs.inorgchem.2c02685
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• Ricci F, Gitto R, Pitasi G, De Luca L. In Silico Insights towards the Identification of SARS-CoV-2 NSP13 Helicase Druggable Pockets. Biomolecules. 2022;12(4):482. Published 2022 Mar 22. doi:10.3390/biom12040482
• El Hassab MA, Eldehna WM, Al-Rashood ST, et al. Multi-stage structure-based virtual screening approach towards identification of potential SARS-CoV-2 NSP13 helicase inhibitors. J Enzyme Inhib Med Chem. 2022;37(1):563-572. doi:10.1080/14756366.2021.2022659
• Berta D, Badaoui M, Martino SA, et al. Modelling the active SARS-CoV-2 helicase complex as a basis for structure-based inhibitor design. Chem Sci. 2021;12(40):13492-13505. Published 2021 Sep 6. doi:10.1039/d1sc02775a

• Newman JA, Douangamath A, Yadzani S, et al. Structure, mechanism and crystallographic fragment screening of the SARS-CoV-2 NSP13 helicase. Nat Commun. 2021;12(1):4848.doi:10.1038/s41467-021-25166-6
• Chen J, Wang Q, Malone B, et al. Ensemble cryo-EM reveals conformational states of the nsp13 helicase in the SARS-CoV-2 helicase replication-transcription complex. Nat Struct Mol Biol. 2022;29(3):250-260. doi:10.1038/s41594-022-00734-6

• Zeng J, Weissmann F, Bertolin AP, et al. Identifying SARS-CoV-2 antiviral compounds by screening for small molecule inhibitors of nsp13 helicase. Biochem J. 2021;478(13):2405-2423
• Lu L, Peng Y, Yao H, et al. Punicalagin as an allosteric NSP13 helicase inhibitor potently suppresses SARS-CoV-2 replication in vitro. Antiviral Res. 2022;206:105389. doi:10.1016/j.antiviral.2022.105389
• Yazdi AK, Pakarian P, Perveen S, et al. Kinetic Characterization of SARS-CoV-2 nsp13 ATPase Activity and Discovery of Small-Molecule Inhibitors. ACS Infect Dis. 2022;8(8):1533-1542. doi:10.1021/acsinfecdis.2c00165
• Corona A, Wycisk K, Talarico C, et al. Natural Compounds Inhibit SARS-CoV-2 nsp13 Unwinding and ATPase Enzyme Activities. ACS Pharmacol Transl Sci. 2022;5(4):226-239. Published 2022 Apr 1. doi:10.1021/acsptsci.1c00253
• Perez-Lemus GR, Menéndez CA, Alvarado W, Byléhn F, de Pablo JJ. Toward wide-spectrum antivirals against coronaviruses: Molecular characterization of SARS-CoV-2 NSP13 helicase inhibitors. Sci Adv. 2022;8(1):eabj4526. doi:10.1126/sciadv.abj4526

• 6ZSL – Crystal structure of the SARS-CoV-2 helicase at 1.94 Angstrom resolution
• 7NIO Crystal structure of the SARS-CoV-2 helicase APO form
• 7NNO Crystal structure of the SARS-CoV-2 helicase in complex with AMP-PNP
• 7RDX – SARS-CoV-2 replication-transcription complex bound to nsp13 helicase – nsp13(2)-RTC – apo class
• 7RDZ – SARS-CoV-2 replication-transcription complex bound to nsp13 helicase – nsp13(2)-RTC – open class