Stabilization of the Dimeric State of SARS-CoV-2 Main Protease by GC376 and Nirmatrelvir

Article Biochemical Research Methods

Characterization of the non-covalent interaction between the PF-07321332 inhibitor and the SARS-CoV-2 main protease

Marina Macchiagodena et al.

Summary: The study examined the non-covalent interaction between PF-07321332 and the SARS-CoV-2 main protease using computational methods. It found that the binding is likely to be stronger when the catalytic dyad is in a neutral state.

JOURNAL OF MOLECULAR GRAPHICS & MODELLING (2022)

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Letter Cell Biology

Crystal structure of SARS-CoV-2 main protease in complex with protease inhibitor PF-07321332

Yao Zhao et al.

PROTEIN & CELL (2022)

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Editorial Material Chemistry, Multidisciplinary

The Path to Paxlovid

Bethany Halford

ACS CENTRAL SCIENCE (2022)

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Article Biology

Modulation of the monomer-dimer equilibrium and catalytic activity of SARS-CoV-2 main protease by a transition-state analog inhibitor

Nashaat T. Nashed et al.

Summary: This study assesses the impact of dimer formation on the catalytic activity of SARS-CoV-2 main protease. The results show that the addition of an inhibitor can increase the catalytic activity, but too high concentrations can decrease the activity. These findings reveal the correlation between dimer formation and enzymatic activity, providing a strategy for designing new drugs.

COMMUNICATIONS BIOLOGY (2022)

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Article Chemistry, Medicinal

Targeting SARS-CoV-2 Main Protease for Treatment of COVID-19: Covalent Inhibitors Structure-Activity Relationship Insights and Evolution Perspectives

Gabriele La Monica et al.

Summary: This perspective analyzes the current research status of covalent SARS-CoV-2 MPRO inhibitors, including different categories of drugs, their mechanisms, and the roles of pharmacophoric moieties and chiral carbons. The provided analyses of noncovalent and covalent in vitro protocols are helpful for the scientific community to discover more efficient inhibitors.

JOURNAL OF MEDICINAL CHEMISTRY (2022)

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Article Biophysics

The Molecular Mechanism of Domain Swapping of the C-Terminal Domain of the SARS-Coronavirus Main Protease

Vishram L. Terse et al.

Summary: Domain swapping is crucial for increasing structural complexity or functional avidity in viral proteins, including the main protease of SARS coronavirus. Understanding the mechanism of domain swapping may offer insights into anti-viral drug design.

BIOPHYSICAL JOURNAL (2021)

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Article Biochemistry & Molecular Biology

Allosteric Regulation of 3CL Protease of SARS-CoV-2 and SARS-CoV Observed in the Crystal Structure Ensemble

Akinori Kidera et al.

Summary: This study highlights the potential therapeutic target of SARS-CoV-2 3CL(pro) for COVID-19 and analyzes its dynamic regulation. By examining the crystal structure ensemble, the motion characteristics of loops like C-loop and ligand binding sites were identified, as well as the impact of the T285A mutation on conformation.

JOURNAL OF MOLECULAR BIOLOGY (2021)

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Article Multidisciplinary Sciences

An oral SARS-CoV-2 Mpro inhibitor clinical candidate for the treatment of COVID-19

Dafydd R. Owen et al.

Summary: PF-07321332, an orally bioavailable SARS-CoV-2 main protease inhibitor, has been discovered with in vitro pan-human coronavirus antiviral activity and excellent off-target selectivity and in vivo safety profiles. This new drug has shown promise in countering the threat of COVID-19 with its oral activity and safety in clinical trials.

SCIENCE (2021)

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Article Multidisciplinary Sciences

The dimer-monomer equilibrium of SARS-CoV-2 main protease is affected by small molecule inhibitors

Lucia Silvestrini et al.

Summary: The study investigated the structural features and thermodynamics of the SARS-CoV-2 M-pro protein using Small Angle X-ray Scattering (SAXS), providing key information for therapeutic intervention. It was found that small molecule inhibitors can affect dimerization and enzymatic activity of M-pro to varying extents, potentially serving as leads for antiviral drug development.

SCIENTIFIC REPORTS (2021)

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Article Biochemistry & Molecular Biology

N-Terminal Finger Stabilizes the S1 Pocket for the Reversible Feline Drug GC376 in the SARS-CoV-2 Mpro Dimer

Elena Arutyunova et al.

Summary: The main protease of SARS-CoV-2 is a high priority drug target, and GC376 has been shown to effectively inhibit it. GC376 also demonstrates reversible binding and broad specificity, making it suitable for clinical trials. The stability and thermodynamic parameters of the protease were studied, revealing insights into the physical chemical properties of viral enzymes.

JOURNAL OF MOLECULAR BIOLOGY (2021)

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Article Biochemistry & Molecular Biology

Repurposing the HCV NS3-4A protease drug boceprevir as COVID-19 therapeutics

Rick Oerlemans et al.

Summary: The rapid growth of COVID-19 cases leads to increasing deaths and economic paralysis. Drug repurposing is a potential short-term solution, while vaccination is a middle-term solution. Research suggests that the HCV drug boceprevir may be repurposed for COVID-19 and other coronaviral infections.

RSC MEDICINAL CHEMISTRY (2021)

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Editorial Material Microbiology