9BVU

NMR structure of TLP-2 in solution

Summary for 9BVU

• Entry DOI: 10.2210/pdb9bvu/pdb
• NMR Information: BMRB: 31174
• Descriptor: Temporin-1Tl (1 entity in total)
• Functional Keywords: antiviral protein
• Biological source: Rana temporaria (common frog)
• Total number of polymer chains: 1
• Total formula weight: 1904.22

Authors

Jia, R.,McShan, A.C.,Stewart, J.,Halim, M. (deposition date: 2024-05-20, release date: 2024-06-05, Last modification date: 2025-10-29)

Primary citation

Stewart, J.,Jia, R.,Ali, M.A.,Williams, B.,Stone, K.,Faddis, R.,Hossain, M.S.,McShan, A.C.,Hossain, M.A.,Halim, M.A.
Structure-Guided Temporin L Analogs Development to Inhibit the Main Protease of SARS-CoV‐2.
Acs Med.Chem.Lett., 16:1963-1970, 2025

PubMed Abstract: Peptide-based inhibitors exhibit considerable potential as antiviral agents targeting SARS-CoV-2. In this study, we designed analogs (TLP-1, TLP-2, and TLP-3) of Temporin L (TL) peptide with the specific objective of selectively interacting with and targeting the main protease (Mpro) of SARS-CoV-2. The synthesis and characterization of TLPs were employed using solid-phase peptide synthesis and LC-MS respectively. CD and solution NMR spectroscopy elucidated the overall structure of the TLPs relative to TL, revealing folded peptides where introduced mutations alter the peptide conformation for binding to Mpro. MD simulations highlighted improvements in TLP's stability and interactions with Mpro. FRET based protease activity assays provided evidence that TLPs exhibited enhanced inhibitory activity against Mpro. The results of our study reveal the promising prospects of TLPs as attractive candidates for investigations, thereby contributing to the progress of peptide-based therapeutic approaches targeting SARS-CoV-2.

PubMed: 41089481
DOI: 10.1021/acsmedchemlett.5c00370

Experimental method

SOLUTION NMR