# Structure-Guided Temporin L Analogs Development to Inhibit the Main Protease of SARS-CoV‑2

## TL;DR

Scientists designed new Temporin L analogs to inhibit the main protease of SARS-CoV-2, showing promise as potential antiviral agents.

## Contribution

The study introduces novel Temporin L analogs with improved stability and inhibitory activity against SARS-CoV-2's main protease.

## Key findings

- TLP analogs showed enhanced inhibitory activity against SARS-CoV-2 Mpro in FRET assays.
- MD simulations revealed improved stability and interactions of TLPs with Mpro.
- Structural analysis showed mutations altered peptide conformation for better Mpro binding.

## 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 in vivo investigations, thereby contributing
to the progress of peptide-based therapeutic approaches targeting
SARS-CoV-2.