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NMR 1H,19F-based screening of the four stem-looped structure 5_SL1-SL4 located in the 5'-untranslated region of SARS-CoV 2 RNA.

Publication ,  Journal Article
Hymon, D; Martins, J; Richter, C; Sreeramulu, S; Wacker, A; Ferner, J; Patwardhan, NN; Hargrove, AE; Schwalbe, H
Published in: RSC medicinal chemistry
January 2024

Development of new antiviral medication against the beta-coronavirus SARS-CoV-2 (SCoV2) is actively being pursued. Both NMR spectroscopy and crystallography as structural screening technologies have been utilised to screen the viral proteome for binding to fragment libraries. Here, we report on NMR screening of elements of the viral RNA genome with two different ligand libraries using 1H-NMR-screening experiments and 1H and 19F NMR-screening experiments for fluorinated compounds. We screened against the 5'-terminal 119 nucleotides located in the 5'-untranslated region of the RNA genome of SCoV2 and further dissected the four stem-loops into its constituent RNA elements to test specificity of binding of ligands to shorter and longer viral RNA stretches. The first library (DRTL-F library) is enriched in ligands binding to RNA motifs, while the second library (DSI-poised library) represents a fragment library originally designed for protein screening. Conducting screens with two different libraries allows us to compare different NMR screening methodologies, describe NMR screening workflows, validate the two different fragment libraries, and derive initial leads for further downstream medicinal chemistry optimisation.

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Published In

RSC medicinal chemistry

DOI

EISSN

2632-8682

ISSN

2632-8682

Publication Date

January 2024

Volume

15

Issue

1

Start / End Page

165 / 177
 

Citation

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Hymon, D., Martins, J., Richter, C., Sreeramulu, S., Wacker, A., Ferner, J., … Schwalbe, H. (2024). NMR 1H,19F-based screening of the four stem-looped structure 5_SL1-SL4 located in the 5'-untranslated region of SARS-CoV 2 RNA. RSC Medicinal Chemistry, 15(1), 165–177. https://doi.org/10.1039/d3md00322a
Hymon, Daniel, Jason Martins, Christian Richter, Sridhar Sreeramulu, Anna Wacker, Jan Ferner, Neeraj N. Patwardhan, Amanda E. Hargrove, and Harald Schwalbe. “NMR 1H,19F-based screening of the four stem-looped structure 5_SL1-SL4 located in the 5'-untranslated region of SARS-CoV 2 RNA.RSC Medicinal Chemistry 15, no. 1 (January 2024): 165–77. https://doi.org/10.1039/d3md00322a.
Hymon D, Martins J, Richter C, Sreeramulu S, Wacker A, Ferner J, et al. NMR 1H,19F-based screening of the four stem-looped structure 5_SL1-SL4 located in the 5'-untranslated region of SARS-CoV 2 RNA. RSC medicinal chemistry. 2024 Jan;15(1):165–77.
Hymon, Daniel, et al. “NMR 1H,19F-based screening of the four stem-looped structure 5_SL1-SL4 located in the 5'-untranslated region of SARS-CoV 2 RNA.RSC Medicinal Chemistry, vol. 15, no. 1, Jan. 2024, pp. 165–77. Epmc, doi:10.1039/d3md00322a.
Hymon D, Martins J, Richter C, Sreeramulu S, Wacker A, Ferner J, Patwardhan NN, Hargrove AE, Schwalbe H. NMR 1H,19F-based screening of the four stem-looped structure 5_SL1-SL4 located in the 5'-untranslated region of SARS-CoV 2 RNA. RSC medicinal chemistry. 2024 Jan;15(1):165–177.

Published In

RSC medicinal chemistry

DOI

EISSN

2632-8682

ISSN

2632-8682

Publication Date

January 2024

Volume

15

Issue

1

Start / End Page

165 / 177