Structural Basis of the Main Proteases of Coronavirus Bound to Drug Candidate PF-07321332
Jian Li, Cheng‐Wen Lin, Xuelan Zhou, Fanglin Zhong, Pei Zeng, Yang Yang, Yuting Zhang, Bo Yu, Xiaona Fan, Peter J. McCormick, Rui Fu, Yang Fu, Haihai Jiang, Jin Zhang
Abstract
The current pandemic of multiple variants has created an urgent need for effective inhibitors of SARS-CoV-2 to complement vaccine strategies. PF-07321332, developed by Pfizer, is the first orally administered coronavirus-specific main protease inhibitor approved by the FDA. We solved the crystal structures of the main protease of SARS-CoV-2, SARS-CoV, and MERS-CoV that bound to the PF-07321332, suggesting PF-07321332 is a broad-spectrum inhibitor for coronaviruses. Structures of the main protease inhibitor complexes present an opportunity to discover safer and more effective inhibitors for COVID-19.