Abstract
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.
Keywords: SARS-CoV-2; Spike protein; allosteric drugs; allosteric effects of mutations; allostery; drug design; druggability; mutability.
【저자키워드】 SARS-CoV-2, drug design, druggability, Spike protein, Allostery, allosteric drugs, allosteric effects of mutations, mutability., 【초록키워드】 Vaccine, pandemic, Mutation, spike, drug design, VoC, variants of concern, drugs, Viral proteins, drug, druggability, diagnostics, Spike protein, Protein, RNA viruses, SARS-CoV-2 spike protein, VOCs, mutability, mechanisms, characteristic, disease, escape mutation, binding, Signaling, Endemic, Endemic disease, Viral protein, while, recent, allosteric effects, addition, RNA virus, determine, the spike protein, allosteric effect, distal, the SARS-CoV-2, 【제목키워드】 spike, Protein, Perspective, the SARS-CoV-2,