ArticleInternational journal of molecular sciences2020
Structural and Evolutionary Analysis Indicate That the SARS-CoV-2 Mpro Is a Challenging Target for Small-Molecule Inhibitor Design.
Article in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.
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Who cites it
94 citing papers in PubMed.
- Heat Shock Protein Inhibitor Tanespimycin (17AAG) Suppresses SARS-CoV-2 Main Protease Activity and Is More Potent Than Clinically Approved Antiviral Nirmatrelvir.Chembiochem : a European journal of chemical biology · 2026Article
- Differential Impact of Substrate Peptides on Interdomain Interactions in Severe Acute Respiratory Syndrome Coronavirus 2 Main Protease.Computational and structural biotechnology journal · 2026Article
- Chromene-Thiazole Derivatives as Potential SARS-CoV‑2 MACS omega · 2025Article
- Exploring covalent inhibitors of SARS-CoV-2 main protease: from peptidomimetics to novel scaffolds.Journal of enzyme inhibition and medicinal chemistry · 2025Review
- Unlocking the potential of phytochemicals in inhibiting SARS-CoV-2 MScientific reports · 2025Article
- Aptamer-engaged nanotherapeutics against SARS-CoV-2.Discover nano · 2025Review
- Molecular docking and molecular dynamics simulation studies of thiazole-coumarin and thiazole-triazole conjugates against MIn silico pharmacology · 2025Article
- Insights into SARS-CoV-2: Small-Molecule Hybrids for COVID-19 Treatment.Molecules (Basel, Switzerland) · 2024Review
- Article
- Breaking the Chain: Protease Inhibitors as Game Changers in Respiratory Viruses Management.International journal of molecular sciences · 2024Review
- Role of marine natural products in the development of antiviral agents against SARS-CoV-2: potential and prospects.Marine life science & technology · 2024Review
- Identification of compounds from natural Peruvian sources as potential inhibitors of SARS-CoV-2 Mpro mutations by virtual screening and computational simulations.F1000Research · 2024Article
- Unsupervised deep learning for molecular dynamics simulations: a novel analysis of protein-ligand interactions in SARS-CoV-2 MRSC advances · 2023Article
- Recent Advances in SARS-CoV-2 Main Protease Inhibitors: From Nirmatrelvir to Future Perspectives.Biomolecules · 2023Review
- Dock-able linear and homodetic di, tri, tetra and pentapeptide library from canonical amino acids: SARS-CoV-2 Mpro as a case study.Journal of pharmaceutical analysis · 2023Article
- Structural analysis of the coronavirus main protease for the design of pan-variant inhibitors.Scientific reports · 2023Article
- Review
- Antitarget, Anti-SARS-CoV-2 Leads, Drugs, and the Drug Discovery-Genetics Alliance Perspective.Journal of medicinal chemistry · 2023Review
- SARS-CoV-2 and its new variants: a comprehensive review on nanotechnological application insights into potential approaches.Applied nanoscience · 2023Review
- Geometry-Based versus Small-Molecule Tracking Method for Tunnel Identification: Benefits and Pitfalls.Journal of chemical information and modeling · 2022Article
34 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors.
Funding
Abstract
The novel coronavirus whose outbreak took place in December 2019 continues to spread at a rapid rate worldwide. In the absence of an effective vaccine, inhibitor repurposing or de novo drug design may offer a longer-term strategy to combat this and future infections due to similar viruses. Here, we report on detailed classical and mixed-solvent molecular dynamics simulations of the main protease (Mpro) enriched by evolutionary and stability analysis of the protein. The results were compared with those for a highly similar severe acute respiratory syndrome (SARS) Mpro protein. In spite of a high level of sequence similarity, the active sites in both proteins showed major differences in both shape and size, indicating that repurposing SARS drugs for COVID-19 may be futile. Furthermore, analysis of the binding site's conformational changes during the simulation time indicated its flexibility and plasticity, which dashes hopes for rapid and reliable drug design. Conversely, structural stability of the protein with respect to flexible loop mutations indicated that the virus' mutability will pose a further challenge to the rational design of small-molecule inhibitors. However, few residues contribute significantly to the protein stability and thus can be considered as key anchoring residues for Mpro inhibitor design.
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Registered trials
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