The severe acute respiratory syndrome (SARS) coronavirus 3CL protease is an attractive target for the development of anti-SARS drugs. In this paper, cinanserin (1) analogs were synthesized and tested for the inhibitory activities against SARS-coronavirus (CoV) 3CL protease by fluorescence resonance energy transfer (FRET) assay. Four analogs show significant activities, especially compound 26 with an IC(50) of 1.06 microM.
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http://dx.doi.org/10.1248/cpb.56.1400 | DOI Listing |
Nat Commun
January 2025
Department of Chemistry, Columbia University, New York, NY, USA.
Variants of SARS-CoV-2 have continued to emerge across the world and cause hundreds of deaths each week. Due to the limited efficacy of vaccines against SARS-CoV-2 and resistance to current therapies, additional anti-viral therapeutics with pan-coronavirus activity are of high interest. Here, we screen 2.
View Article and Find Full Text PDFJ Am Chem Soc
January 2025
Department of Biochemistry and Biophysics, Texas A&M University, 301 Old Main Drive, College Station, Texas 77845, United States.
SARS-CoV-2 3CL protease (Main protease) and human cathepsin L are proteases that play unique roles in the infection of human cells by SARS-CoV-2, the causative agent of COVID-19. Both proteases recognize leucine and other hydrophobic amino acids at the P position of a peptidomimetic inhibitor. At the P position, cathepsin L accepts many amino acid side chains, with a partial preference for phenylalanine, while 3CL-PR protease has a stringent specificity for glutamine or glutamine analogues.
View Article and Find Full Text PDFSci Rep
December 2024
Laboratory of Bioinorganic Chemistry, Department of Pharmacy and Biotechnology, University of Bologna, 40127, Bologna, Italy.
This manuscript details the application of Isothermal Titration Calorimetry (ITC) to characterize the kinetics of 3CL, the main protease from the Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2), and its inhibition by Ensitrelvir, a known non-covalent inhibitor. 3CL is essential for producing the proteins necessary for viral infection, which led to the COVID-19 pandemic. The ITC-based assay provided rapid and reliable measurements of 3CL activity, allowing for the direct derivation of the kinetic enzymatic constants K and k by monitoring the thermal power required to maintain a constant temperature as the substrate is consumed.
View Article and Find Full Text PDFACS Catal
December 2024
Departments of Biochemistry and Biophysics, Texas A&M University, College Station, Texas 77843, United States.
J Biomol Struct Dyn
December 2024
Department of Pharmacognosy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Alkharj, Saudi Arabia.
The COVID-19 pandemic caused by the novel coronavirus, SARS-CoV-2, has been a global threat affecting the entire world. It is a single-stranded RNA virus that belongs to the coronavirus family. In SARS-CoV2, the 3CL protease protein significantly contributes to viral replication and is responsible for viral polyprotein cleavage.
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