Abstract
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.
Highlights
IntroductionThe Severe Acute Respiratory Syndrome—Coronavirus-2 (SARS-CoV-2), first detected in December 2019 in the Wuhan province of China, has caused the COVID-19 pandemic
While in this study we have focused on the mutations within the receptor binding domain (RBD) of spike protein, the D614G mutation has already been reported to increase the binding affinity with hACE2 and is susceptible to neutralization by antibodies [26]
We have aimed to investigate the thermodynamic effects of the mutations in the RBD region of the spike glycoprotein interacting with hACE2 and compare that with the wildtype
Summary
The Severe Acute Respiratory Syndrome—Coronavirus-2 (SARS-CoV-2), first detected in December 2019 in the Wuhan province of China, has caused the COVID-19 pandemic. As of August 18, 2021, there are more than 208,470,375 confirmed cases, and 4,377,979 people have lost their lives (https://covid19.who.int/) (accessed on 18 August 2021). The SARSCoV-2 belongs to the family of beta corona virus, the same class of viruses responsible for previous pandemics caused by SARS-CoV and MERS [1,2,3]. SARS-CoV-2 possesses a large single-stranded RNA as genetic material and has four main structural components, namely, Envelope protein, spike protein, membrane protein and nucleocapsid [4,5,6]. The main structural element that enables this virus to attach to the host receptor is the spike glycoprotein, and it gives the crown-like appearance to the virus, it is named Coronavirus [7,8,9]
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