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Article

Possible Link between Higher Transmissibility of Alpha, Kappa and Delta Variants of SARS-CoV-2 and Increased Structural Stability of Its Spike Protein and hACE2 Affinity

1
Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology (IIT) Delhi, New Delhi 110016, India
2
Department of Life Science, School of Basic Sciences and Research, Sharda University, Greater Noida 201301, India
*
Authors to whom correspondence should be addressed.
Academic Editors: Istvan Simon and Csaba Magyar
Int. J. Mol. Sci. 2021, 22(17), 9131; https://doi.org/10.3390/ijms22179131
Received: 13 July 2021 / Revised: 20 August 2021 / Accepted: 22 August 2021 / Published: 24 August 2021
(This article belongs to the Special Issue Frontiers in Protein Structure Research)
The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) outbreak in December 2019 has caused a global pandemic. The rapid mutation rate in the virus has created alarming situations worldwide and is being attributed to the false negativity in RT-PCR tests. It has also increased the chances of reinfection and immune escape. Recently various lineages namely, B.1.1.7 (Alpha), B.1.617.1 (Kappa), B.1.617.2 (Delta) and B.1.617.3 have caused rapid infection around the globe. To understand the biophysical perspective, we have performed molecular dynamic simulations of four different spikes (receptor binding domain)-hACE2 complexes, namely wildtype (WT), Alpha variant (N501Y spike mutant), Kappa (L452R, E484Q) and Delta (L452R, T478K), and compared their dynamics, binding energy and molecular interactions. Our results show that mutation has caused significant increase in the binding energy between the spike and hACE2 in Alpha and Kappa variants. In the case of Kappa and Delta variants, the mutations at L452R, T478K and E484Q increased the stability and intra-chain interactions in the spike protein, which may change the interaction ability of neutralizing antibodies to these spike variants. Further, we found that the Alpha variant had increased hydrogen interaction with Lys353 of hACE2 and more binding affinity in comparison to WT. The current study provides the biophysical basis for understanding the molecular mechanism and rationale behind the increase in the transmissivity and infectivity of the mutants compared to wild-type SARS-CoV-2. View Full-Text
Keywords: B.1.1.7; B.1.617.2; COVID-19; E484Q; T478K and L452R mutation; N501Y mutation; spike protein B.1.1.7; B.1.617.2; COVID-19; E484Q; T478K and L452R mutation; N501Y mutation; spike protein
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MDPI and ACS Style

Kumar, V.; Singh, J.; Hasnain, S.E.; Sundar, D. Possible Link between Higher Transmissibility of Alpha, Kappa and Delta Variants of SARS-CoV-2 and Increased Structural Stability of Its Spike Protein and hACE2 Affinity. Int. J. Mol. Sci. 2021, 22, 9131. https://doi.org/10.3390/ijms22179131

AMA Style

Kumar V, Singh J, Hasnain SE, Sundar D. Possible Link between Higher Transmissibility of Alpha, Kappa and Delta Variants of SARS-CoV-2 and Increased Structural Stability of Its Spike Protein and hACE2 Affinity. International Journal of Molecular Sciences. 2021; 22(17):9131. https://doi.org/10.3390/ijms22179131

Chicago/Turabian Style

Kumar, Vipul, Jasdeep Singh, Seyed E. Hasnain, and Durai Sundar. 2021. "Possible Link between Higher Transmissibility of Alpha, Kappa and Delta Variants of SARS-CoV-2 and Increased Structural Stability of Its Spike Protein and hACE2 Affinity" International Journal of Molecular Sciences 22, no. 17: 9131. https://doi.org/10.3390/ijms22179131

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