Westlake University Develops High-Throughput Platform for Covalent Protein Therapies
Researchers at Westlake University in China have developed a high-throughput platform for engineering fast-acting covalent protein therapeutics. This platform aims to address the kinetic mismatch in covalent protein drugs, which are typically cleared rapidly in vivo while forming slow covalent bonds. The new system combines yeast surface display with chemoselective protein modification, allowing for rapid and irreversible target engagement. The platform has been used to develop a covalent antagonist targeting PD-L1, named IB101, which shows strong antitumor activity in mouse models. Additionally, it has been applied to cytokine engineering, resulting in a covalent IL-18 variant, IB201, which enhances signaling strength and duration. The platform also demonstrated versatility by developing a covalent inhibitor targeting the receptor-binding domain of SARS-CoV-2, showing durable viral neutralization. 
