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Basic Characteristics of Mutations
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Mutation Site
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T487K |
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Mutation Site Sentence
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L452 and T487 which are mutated to L452R in Delta and T487K in both variants showed the highest energy for the Delta variant with the value of -10.76 kcal/mol (L452R) and -10.38 kcal/mol (T487K) by mediating a consistent hydrogen bond. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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Standardized Encoding Gene
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Genotype/Subtype
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Delta |
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Viral Reference
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EPI ISL 8240498;EPI ISL 7542798
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Functional Impact and Mechanisms
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Disease
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-
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Immune
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- |
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Target Gene
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-
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
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- |
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Location
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Pakistan |
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Literature Information
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PMID
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35755247
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Title
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Deciphering the Impact of Mutations on the Binding Efficacy of SARS-CoV-2 Omicron and Delta Variants With Human ACE2 Receptor
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Author
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Khan A,Khan SA,Zia K,Altowyan MS,Barakat A,Ul-Haq Z
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Journal
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Frontiers in chemistry
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Journal Info
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2022 Jun 8;10:892093
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Abstract
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The pandemic of COVID-19, caused by SARS-CoV-2, has globally affected the human health and economy. Since the emergence of the novel coronavirus SARS-CoV-2, the life-threatening virus continues to mutate and evolve. Irrespective of acquired natural immunity and vaccine-induced immunity, the emerging multiple variants are growing exponentially, crossing the territorial barriers of the modern world. The rapid emergence of SARS-CoV-2 multiple variants challenges global researchers regarding the efficacy of available vaccines and variant transmissibility. SARS-CoV-2 surface-anchored S-protein recognizes and interacts with the host-cell ACE2, facilitating viral adherence and entrance into the cell. Understanding the interfacial interactions between the spike protein of SARS-CoV-2 variants and human ACE2 receptor is important for the design and development of antiviral therapeutics against SARS-CoV-2 emerging variants. Despite extensive research, the crucial determinants related to the molecular interactions between the spike protein of SARS-CoV-2 variants and host receptors are poorly understood. Thus, in this study, we explore the comparative interfacial binding pattern of SARS-CoV-2 spike RBD of wild type, Delta, and Omicron with the human ACE2 receptor to determine the crucial determinants at the atomistic level, using MD simulation and MM/GBSA energy calculations. Based on our findings, the substitution of Q493R, G496S, Q498R, and Y505H induced internal conformational changes in Omicron spike RBD, which leads to higher binding affinity than Delta spike RBD with the human ACE2 receptor, eventually contributing to higher transmission and infectivity. Taken together, these results could be used for the structure-based design of effective antiviral therapeutics against SARS-CoV-2 variants.
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Sequence Data
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-
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