SARS-CoV-2 Spike Mutations, L452R, T478K, E484Q and P681R, in the Second Wave of COVID-19 in Maharashtra, India.

Sarah Cherian,Nic Team,Mousumi Das,Partha Rakshit,Sujeet Singh,Samiran Panda,Santosh Jadhav,Pragya Yadav,Priya Abraham,Nivedita Gupta,Varsha Potdar

doi:10.3390/microorganisms9071542

Abstract

As the global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic expands, genomic epidemiology and whole genome sequencing are being used to investigate its transmission and evolution. Against the backdrop of the global emergence of “variants of concern” (VOCs) during December 2020 and an upsurge in a state in the western part of India since January 2021, whole genome sequencing and analysis of spike protein mutations using sequence and structural approaches were undertaken to identify possible new variants and gauge the fitness of the current circulating strains. Phylogenetic analysis revealed that newly identified lineages B.1.617.1 and B.1.617.2 were predominantly circulating. The signature mutations possessed by these strains were L452R, T478K, E484Q, D614G and P681R in the spike protein, including within the receptor-binding domain (RBD). Of these, the mutations at residue positions 452, 484 and 681 have been reported in other globally circulating lineages. The structural analysis of RBD mutations L452R, T478K and E484Q revealed that these may possibly result in increased ACE2 binding while P681R in the furin cleavage site could increase the rate of S1-S2 cleavage, resulting in better transmissibility. The two RBD mutations, L452R and E484Q, indicated decreased binding to select monoclonal antibodies (mAbs) and may affect their neutralization potential. Further in vitro/in vivo studies would help confirm the phenotypic changes of the mutant strains. Overall, the study revealed that the newly emerged variants were responsible for the second wave of COVID-19 in Maharashtra. Lineage B.1.617.2 has been designated as a VOC delta and B.1.617.1 as a variant of interest kappa, and they are being widely reported in the rest of the country as well as globally. Continuous monitoring of these and emerging variants in India is essential.

Highlights

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surface spike (S) protein mediates entry into host cells by binding to the host receptor angiotensinconverting enzyme 2 (ACE2) via its receptor-binding domain (RBD)
Among the new B.1.617 lineages, B.1.617.1 included the majority of the strains from eastern part of Maharashtra while B.1.617.2 included sequences from major cities like Pune, Thane and Mumbai in the western part of the state
A synonymous mutation D111D was observed to be co-occurring with the RBD mutations L452R and E484Q in lineage B.1.617.1

Summary

Introduction

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surface spike (S) protein mediates entry into host cells by binding to the host receptor angiotensinconverting enzyme 2 (ACE2) via its receptor-binding domain (RBD). Crystal structures of SARS-CoV-2 S protein or its RBD complexed with ACE2 from different hosts reveal that the RBD contains a core and a receptor-binding motif (RBM) which forms contacts with. A number of naturally selected mutations in the RBM have been shown to affect infectivity, human-to-human transmission, pathogenesis and immune escape [2]. As the global SARS-CoV-2 pandemic expands, genomic epidemiology and whole genome sequencing are being used to investigate the transmission and evolution. Clades G/GH/GR/GV/GRY as per the Global Initiative on Sharing All Influenza Data (GISAID) database

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Conclusion