Exploration of P1 and P4 modifications of nirmatrelvir: Design, synthesis, biological evaluation, and X-ray structural studies of SARS-CoV-2 Mpro inhibitors

Affiliations

• 1 Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, IN, 47907, USA; Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN, 47907, USA. Electronic address: akghosh@purdue.edu.
• 2 Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, IN, 47907, USA.
• 3 Department of Biochemistry, Purdue University, West Lafayette, IN, 47907, USA.
• 4 Department of Biological Sciences, Purdue University, West Lafayette, IN, 47907, USA.
• 5 Department of Refractory Viral Diseases, National Center for Global Health and Medicine, Shinjuku, Tokyo, 162-8655, Japan.
• 6 Department of Clinical Retrovirology, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto, 860-0811, Japan.
• 7 Department of Refractory Viral Diseases, National Center for Global Health and Medicine, Shinjuku, Tokyo, 162-8655, Japan; Department of Infectious Diseases, Kumamoto University School of Medicine, Kumamoto, 860-8556, Japan; Experimental Retrovirology Section, HIV and AIDS Malignancy Branch National Cancer Institute, Bethesda, MD, 20892, USA.
• 8 Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, IN, 47907, USA; Department of Biochemistry, Purdue University, West Lafayette, IN, 47907, USA; Department of Biological Sciences, Purdue University, West Lafayette, IN, 47907, USA.