Delving into the Latest Updates on CTSL inhibitors(The University of Sydney) with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms-

Target

CTSL

Action

inhibitors

Mechanism

CTSL inhibitors(Cathepsin L inhibitors)

Therapeutic Areas

Infectious DiseasesRespiratory Diseases

Active Indication

COVID-19

Inactive Indication-

Originator Organization

The University of Sydney

Active Organization

The University of Sydney

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Author: Tang, Arthur H. ; Stoye, Alexander ; Meek, Thomas D. ; Hook, Vivian ; McKerrow, James H. ; Fajtová, Pavla ; Payne, Richard J. ; Larance, Mark ; Aggarwal, Anupriya ; O’Donoghue, Anthony J. ; Gerwick, William H. ; Beretta, Laura ; Yoon, Michael C. ; Bedding, Max J. ; Pwee, Dustin ; Drelich, Aleksandra ; Ashhurst, Anneliese S. ; Tseng, Chien-Te ; Turville, Stuart ; Skinner, Danielle ; Li, Linfeng

Cathepsin L is a key host cysteine protease utilized by coronaviruses for cell entry and is a promising drug target for novel antivirals against SARS-CoV-2. The marine natural product gallinamide A and several synthetic analogues were identified as potent inhibitors of cathepsin L with IC₅₀ values in the picomolar range. Lead molecules possessed selectivity over other cathepsins and alternative host proteases involved in viral entry. Gallinamide A directly interacted with cathepsin L in cells and, together with two lead analogues, potently inhibited SARS-CoV-2 infection in vitro, with EC₅₀ values in the nanomolar range. Reduced antiviral activity was observed in cells overexpressing transmembrane protease, serine 2 (TMPRSS2); however, a synergistic improvement in antiviral activity was achieved when combined with a TMPRSS2 inhibitor. These data highlight the potential of cathepsin L as a COVID-19 drug target as well as the likely need to inhibit multiple routes of viral entry to achieve efficacy.

100 Deals associated with CTSL inhibitors(The University of Sydney)

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