Dr. Melanie Koehler

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10Years (2017-Present)

(Calculated once Scilit publication data is synced: current year − year of first publication + 1)

Representative Publications

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11 September 2020 in Nature Communications

Journal Article

Molecular interaction and inhibition of SARS-CoV-2 binding to the ACE2 receptor

Jinsung Yang

Simon J. L. Petitjean

Melanie Koehler

Qingrong Zhang

Andra C. Dumitru

David Alsteens

Study of the interactions established between the viral glycoproteins and their host receptors is of critical importance for a better understanding of virus entry into cells. The novel coronavirus SARS-CoV-2 entry into host cells is mediated by its spike glycoprotein (S-glycoprotein), and the angiotensin-converting enzyme 2 (ACE2) has been identified as a cellular receptor. Here, we use atomic force microscopy to investigate the mechanisms by which the S-glycoprotein binds to the ACE2 receptor. We demonstrate, both on model surfaces and on living cells, that the receptor binding domain (RBD) serves as the binding interface within the S-glycoprotein with the ACE2 receptor and extract the kinetic and thermodynamic properties of this binding pocket. Altogether, these results provide a picture of the established interaction on living cells. Finally, we test several binding inhibitor peptides targeting the virus early attachment stages, offering new perspectives in the treatment of the SARS-CoV-2 infection.

17 August 2018 in Science

Journal Article

A molecular mechanism for Wnt ligand-specific signaling

Marie Eubelen

Naguissa Bostaille

Pauline Cabochette

Anne Gauquier

Patricia Tebabi

Benoit Vanhollebeke

How Wnt ligands achieve specificity: Wnt signaling is essential for development, tissue homeostasis, and disease. The 19 members of the Wnt family interact promiscuously with the 10 Frizzled receptors, raising the question of how ligand-specific discrimination is achieved in a biological context. Eubelen et al. used experiments in zebrafish to show that cells are equipped with decoding modules that bind Wnt with high specificity and trigger signal amplification via their recruitment into higher-order Frizzled signalosomes (see the Perspective by Kim and Goentoro). Thus, distinct Wnt ligand-receptor pairs can be targeted specifically for therapeutic purposes. Science , this issue p. eaat1178 ; see also p. 643

30 November 2021 in Nature Communications

Journal Article

Molecular insights into receptor binding energetics and neutralization of SARS-CoV-2 variants

Melanie Koehler

Ankita Ray

Rodrigo Azevedo Moreira da Silva

Blinera Juniku

Adolfo B. Poma

David Alsteens

Despite an unprecedented global gain in knowledge since the emergence of SARS-CoV-2, almost all mechanistic knowledge related to the molecular and cellular details of viral replication, pathology and virulence has been generated using early prototypic isolates of SARS-CoV-2. Here, using atomic force microscopy and molecular dynamics, we investigated how these mutations quantitatively affected the kinetic, thermodynamic and structural properties of RBD—ACE2 complex formation. We observed for several variants of concern a significant increase in the RBD—ACE2 complex stability. While the N501Y and E484Q mutations are particularly important for the greater stability, the N501Y mutation is unlikely to significantly affect antibody neutralization. This work provides unprecedented atomistic detail on the binding of SARS-CoV-2 variants and provides insight into the impact of viral mutations on infection-induced immunity.

10 May 2022 in Nature Communications

Journal Article

Multivalent 9-O-Acetylated-sialic acid glycoclusters as potent inhibitors for SARS-CoV-2 infection

Simon J. L. Petitjean

Wenzhang Chen

Melanie Koehler

Ravikumar Jimmidi

Jinsung Yang

David Alsteens

The recent emergence of highly transmissible SARS-CoV-2 variants illustrates the urgent need to better understand the molecular details of the virus binding to its host cell and to develop anti-viral strategies. While many studies focused on the role of the angiotensin-converting enzyme 2 receptor in the infection, others suggest the important role of cell attachment factors such as glycans. Here, we use atomic force microscopy to study these early binding events with the focus on the role of sialic acids (SA). We show that SARS-CoV-2 binds specifically to 9-O-acetylated-SA with a moderate affinity, supporting its role as an attachment factor during virus landing to cell host surfaces. For therapeutic purposes and based on this finding, we have designed novel blocking molecules with various topologies and carrying a controlled number of SA residues, enhancing affinity through a multivalent effect. Inhibition assays show that the AcSA-derived glycoclusters are potent inhibitors of cell binding and infectivity, offering new perspectives in the treatment of SARS-CoV-2 infection.

1 October 2019 in Nature Communications

Journal Article

Glycan-mediated enhancement of reovirus receptor binding

Melanie Koehler

Pavithra Aravamudhan

Camila Guzman-Cardozo

Andra C. Dumitru

Jinsung Yang

David Alsteens

Viral infection is an intricate process that requires the concerted action of both viral and host cell components. Entry of viruses into cells is initiated by interactions between viral proteins and their cell surface receptors. Despite recent progress, the molecular mechanisms underlying the multistep reovirus entry process are poorly understood. Using atomic force microscopy, we investigated how the reovirus σ1 attachment protein binds to both α-linked sialic acid (α-SA) and JAM-A cell-surface receptors. We discovered that initial σ1 binding to α-SA favors a strong multivalent anchorage to JAM-A. The enhanced JAM-A binding by virions following α-SA engagement is comparable to JAM-A binding by infectious subvirion particles (ISVPs) in the absence of α-SA. Since ISVPs have an extended σ1 conformer, this finding suggests that α-SA binding triggers a conformational change in σ1. These results provide new insights into the function of viral attachment proteins in the initiation of infection and open new avenues for the use of reoviruses as oncolytic agents.

5 October 2017 in Nature Protocols

Journal Article

Combining confocal and atomic force microscopy to quantify single-virus binding to mammalian cell surfaces

Richard Newton

Martin Delguste

About Me

Dr. Melanie Koehler received her PhD in Biophysics from the Johannes Kepler University Linz in the laboratory of Prof. Dr. Peter Hinterdorfer. At the end of 2016, she moved to UCLouvain in Belgium, where she worked as a postdoctoral researcher in the nanobiophysics lab of Prof. Dr. David Alsteens. There, she investigated the molecular mechanisms behind virus binding to cell surface receptors. In 2022, she received funding from the Leibniz Association to establish an independent junior research group at the Leibniz Institute of Food Systems Biology at the Technical University of Munich (LSB), where she is now the head of the "Mechanoreceptors" group. Her interdisciplinary research group aims to combine experimental biophysics (mainly atomic force microscopy) with methods from food chemistry and biology to establish a new experimental research platform for food-related research. Her current work aims to unravel the molecular basis of mechanoreceptor-mediated oral texture perception, i.e. mouthfeel. She received the Nestlé Award for Excellence in Flavor Science at the 13th Wartburg Symposium on Flavor Chemistry and Biology.

Dr. Melanie Koehler

Dr. Melanie Koehler

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Representative Publications

About Me