Characterization of mutations modulating enhanced transmissibility of SARS-CoV-2 B.1.617+ (Delta) variant using In Silico tools.
Gene Rep
; 27: 101636, 2022 Jun.
Article
in English
| MEDLINE | ID: covidwho-1885776
ABSTRACT
Since the beginning of the of SARS-CoV-2 (Covid-19) pandemic, variants of concern (VOC) have emerged taxing health systems worldwide. In October 2020, a new variant of SARS-CoV-2 (B.1.617+/Delta variant) emerged in India, triggering a deadly wave of Covid-19. Epidemiological data strongly suggests that B.1.617+ is more transmissible and previous reports have revealed that B.1.617+ has numerous mutations compared to wild type (WT), including several changes in the spike protein (SP). The main goal of this study was to use In Silico (computer simulation) techniques to examine mutations in the SP, specifically L452R and E484Q (part of the receptor binding domain (RBD) for human angiotensin-converting enzyme 2 (hACE2)) and P681R (upstream of the Furin cleavage motif), for effects in modulating the transmissibility of the B.1.617+ variant. Using computational models, the binding free energy (BFE) and H-bond lengths were calculated for SP-hACE2 and SP-Furin complexes. Comparison of the SP-hACE2 complex in the WT and B.1.617+ revealed both complexes have identical receptor-binding modes but the total BFE of B.1.617+ binding was more favorable for complex formation than WT, suggesting L452R and E484Q have a moderate impact on binding affinity. In contrast, the SP-Furin complex of B.1.617+ substantially lowered the BFE and revealed changes in molecular interactions compared to the WT complex, implying stronger complex formation between the variant and Furin. This study provides an insight into mutations that modulate transmissibility of the B.1.617+ variant, specifically the P681R mutation which appears to enhance transmissibility of the B.1.617+ variant by rendering it more receptive to Furin.
B.1.617+; BFE, total binding free energy; Binding affinity; Cleavage; Delta variant; MM/GBSA, Molecular Mechanics with Generalized Born and Surface Area; Molecular interface; PPI, protein-protein interaction; Protein structure; RBD, receptor-binding domain; RMSD, root mean square deviation; SARS-CoV-2; VOC, variants of concern; WT, wild type; hACE2, human angiotensin-converting enzyme 2; Å, Angstrom
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Topics:
Variants
Language:
English
Journal:
Gene Rep
Year:
2022
Document Type:
Article
Affiliation country:
J.genrep.2022.101636
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