SKM 2021 – scientific programme

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SYCO: Symposium The Physics of CoViD Infections

SYCO 1: The Physics of CoViD Infections

SYCO 1.2: Invited Talk

Monday, September 27, 2021, 14:00–14:30, Audimax 1

From molecular simulations towards antiviral therapeutics against COVID-19 — •Rebecca Wade — Heidelberg Institute for Theoretical Studies — ZMBH, Heidelberg University, Germany

Despite advancing vaccination campaigns against COVID-19, the emergence of new variants of SARS-CoV-2 and the difficulties of achieving high vaccination levels demonstrate the importance of developing antiviral therapeutics. During the pandemic, the international computational molecular biophysics community has worked towards this goal by applying simulation techniques to study viral infection and to discover new antiviral agents. One of the challenges for such studies is the highly dynamic nature of virus protein drug targets, such as the main protease and the spike glycoprotein.

To identify inhibitors of the main protease, we applied our TRAPP toolbox (1) to analyze the druggability of ca. 30000 protein conformations and found that small structural variations in the binding site dramatically impact ligand binding (2). Virtual screening against selected conformations led to the prediction and experimental validation of novel inhibitors.

Heparin is used to prevent thrombosis in COVID-19 patients but also has antiviral activity. We are carrying out simulations to investigate how heparin polysaccharide binds to the spike and to design of new heparin derivatives for antiviral therapy. Our results reveal three mechanisms by which heparin can exert its antiviral effects (3).

(1) https://trapp.h-its.org/ (2) Gossen et al., ACS Pharmacol. Transl. Sci. 2021, 4, 1079 - 1095. (3) Paiardi et al., arXiv:2103.07722