Allosteric perspective on the mutability and druggability of the SARS-CoV-2 Spike protein
| Autor: | Firdaus Samsudin, Wei-Ven Tee, Igor N. Berezovsky, Peter J. Bond, Enrico Guarnera, Zhen Wah Tan |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
2019-20 coronavirus outbreak
drug design Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Allosteric regulation Druggability Computational biology Biology Spike protein allosteric effects of mutations Article Structural Biology Humans Molecular Biology Pandemics Endemic disease allostery Distal locations SARS-CoV-2 mutability RNA Spike Protein COVID-19 Drug Treatment allosteric drugs Mutation Spike Glycoprotein Coronavirus druggability |
| Zdroj: | Structure (London, England : 1993) |
| ISSN: | 1878-4186 0969-2126 |
| Popis: | Recent developments in the SARS-CoV-2 pandemic point to its inevitable transformation into an endemic disease, urging both refinement of diagnostics for emerging variants of concern (VOCs) and design of variant-specific drugs in addition to vaccine adjustments. Exploring the structure and dynamics of the SARS-CoV-2 Spike protein, we argue that the high-mutability characteristic of RNA viruses coupled with the remarkable flexibility and dynamics of viral proteins result in a substantial involvement of allosteric mechanisms. While allosteric effects of mutations should be considered in predictions and diagnostics of new VOCs, allosteric drugs advantageously avoid escape mutations via non-competitive inhibition originating from alternative distal locations. The exhaustive allosteric signaling and probing maps presented herein provide a comprehensive picture of allostery in the spike protein, making it possible to locate potential mutations that could work as new VOC “drivers” and to determine binding patches that may be targeted by newly developed allosteric drugs. Graphical abstract Tan et al. characterize the dynamics of the SARS-CoV-2 Spike protein and derive allosteric signaling maps for the spike protein, which is of interest for drug development. The analysis of allosteric effects of spike protein mutations allows the prediction of potential drivers in emerging variants of concern. |
| Databáze: | OpenAIRE |
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