[NMR paper] Repurposing of US-FDA approved drugs against SARS-CoV-2 main protease (Mpro) by using STD-NMR spectroscopy, in silico studies and antiviral assays
SARS-CoV-2 Main protease (M^(pro)) is a well-known drug target against SARS-CoV-2 infection. Identification of M^(pro) inhibitors is vigorously pursued due to its crucial role in viral replication. The present study was aimed to identify M^(pro) inhibitors via repurposing of US-FDA approved drugs by STD-NMR spectroscopy. In this study, 156 drugs and natural compounds were evaluated against M^(pro). Among them, 10 drugs were found to be interacting with M^(pro), including diltiazem HCl (1),...
[NMR paper] NMR Observation of Sulfhydryl Signals in SARS-CoV-2 Main Protease Aids Structural Studies
NMR Observation of Sulfhydryl Signals in SARS-CoV-2 Main Protease Aids Structural Studies
The 68-kDa homodimeric 3C-like protease of SARS-CoV-2, M pro (3CL pro /Nsp5), is a key antiviral drug target. NMR spectroscopy of this large system proved challenging and resonance assignments have remained incomplete. Here we present the near-complete (>97%) backbone assignments of a C145A variant of M pro (M pro C145A ) both with, and without, the N-terminal auto-cleavage substrate sequence, in its native homodimeric state. We also present SILLY, a simple yet effective pseudo-3D NMR experiment...
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[NMR paper] NMR spectroscopy of the main protease of SARS-CoV-2 and fragment-based screening identify three protein hotspots and an antiviral fragment
NMR spectroscopy of the main protease of SARS-CoV-2 and fragment-based screening identify three protein hotspots and an antiviral fragment
The main protease (3CLp) of the SARS-CoV-2, the causative agent for the COVID-19 pandemic, is one of the main targets for drug development. To be active, 3CLp relies on a complex interplay between dimerization, active site flexibility, and allosteric regulation. The deciphering of these mechanisms is a crucial step to enable the search for inhibitors. In this context, using NMR spectroscopy, we studied the conformation of dimeric 3CLp from the...
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09-29-2021 12:23 PM
A COVID moonshot: assessment of ligand binding to the SARS-CoV-2 main protease by saturation transfer difference NMR spectroscopy
A COVID moonshot: assessment of ligand binding to the SARS-CoV-2 main protease by saturation transfer difference NMR spectroscopy
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological cause of the coronavirus disease 2019, for which no effective antiviral therapeutics are available. The SARS-CoV-2 main protease (Mpro) is essential for viral replication and constitutes a promising therapeutic target. Many efforts aimed at deriving effective Mpro inhibitors are currently underway, including an international...
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04-15-2021 12:12 PM
[NMR paper] Intracellular binding/unbinding kinetics of approved drugs to carbonic anhydrase II observed by in-cell NMR.
Intracellular binding/unbinding kinetics of approved drugs to carbonic anhydrase II observed by in-cell NMR.
http://www.bionmr.com//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--pubs.acs.org-images-pubmed-acspubs.jpg Related Articles Intracellular binding/unbinding kinetics of approved drugs to carbonic anhydrase II observed by in-cell NMR.
ACS Chem Biol. 2020 Sep 21;:
Authors: Luchinat E, Barbieri L, Cremonini M, Nocentini A, Supuran CT, Banci L
Abstract
Candidate drugs rationally designed in vitro often fail due to low...
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09-24-2020 07:17 PM
[NMR paper] Discovery of Small-Molecule Inhibitors of Ubiquitin Specific Protease 7 (USP7) Using Integrated NMR and in Silico Techniques.
Discovery of Small-Molecule Inhibitors of Ubiquitin Specific Protease 7 (USP7) Using Integrated NMR and in Silico Techniques.
http://www.bionmr.com//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--pubs.acs.org-images-pubmed-acspubs.jpg Related Articles Discovery of Small-Molecule Inhibitors of Ubiquitin Specific Protease 7 (USP7) Using Integrated NMR and in Silico Techniques.
J Med Chem. 2017 12 28;60(24):10056-10070
Authors: Di Lello P, Pastor R, Murray JM, Blake RA, Cohen F, Crawford TD, Drobnick J, Drummond J, Kategaya L, Kleinheinz T, Maurer T,...
Repurposing of US-FDA approved drugs against SARS-CoV-2 main protease (Mpro) by using STD-NMR spectroscopy, in silico studies and antiviral assays
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