Abstract
The outbreak of COVID-19 across the world has posed unprecedented and global challenges on multiple fronts. Most of the vaccine and drug development has focused on the spike proteins and viral RNA-polymerases and main protease for viral replication. Using the bioinformatics and structural modelling approach, we modelled the structure of the envelope (E)-protein of novel SARS-CoV-2. The E-protein of this virus shares sequence similarity with that of SARS- CoV-1, and is highly conserved in the N-terminus regions. Incidentally, compared to spike proteins, E proteins demonstrate lower disparity and mutability among the isolated sequences. Using homology modelling, we found that the most favorable structure could function as a gated ion channel conducting H+ ions. Combining pocket estimation and docking with water, we determined that GLU 8 and ASN 15 in the N-terminal region were in close proximity to form H-bonds which was further validated by insertion of the E protein in an ERGIC-mimic membrane. Additionally, two distinct "core" structures were visible, the hydrophobic core and the central core, which may regulate the opening/closing of the channel. We propose this as a mechanism of viral ion channeling activity which plays a critical role in viral infection and pathogenesis. In addition, it provides a structural basis and additional avenues for vaccine development and generating therapeutic interventions against the virus.
Highlights
The COVID-19 (CoronaVIrus Disease 2019) is a severe acute respiratory syndrome (SARS) caused by a novel coronavirus, SARS-CoV-2, and has taken the form of a worldwide pandemic in the last few months [1]
We found that leucine (LEU, 0.189 ± 0.132), valine (VAL, 0.25 ± 0.13) and serine (SER, 0.461 ± 0.091) (Fig 1E; indicated by $$) of the E proteins have lower than 50% chance of mutability compared to spike proteins (LEU (0.626 ± 0.004), VAL (0.652 ± 0.004) and SER (0.632 ± 0.006)) (Fig 1E)
Structural determination of proteins using Nuclear magnetic resonance (NMR) spectroscopy provided a set of models of the E protein from SARS-Co-1 (Pdb id: 5X29) having the lower energies (S6A, side view, Fig 6A-ii, top view)
Summary
The COVID-19 (CoronaVIrus Disease 2019) is a severe acute respiratory syndrome (SARS) caused by a novel coronavirus, SARS-CoV-2, and has taken the form of a worldwide pandemic in the last few months [1]. To date (as in 9 July, 2020), this disease has affected nearly 12 million people, resulting in nearly 550 thousand deaths disrupting social and economic structures of nearly 190 nations across the globe with numbers still on the rise [2, 3]. Coronavirus is a positive-sense single-stranded RNA virus belonging to the class of β-coronaviruses of the family Coronaviridae, and affected humans causing different forms of mild. Structural insight into the role of novel SARS-CoV-2 E protein account: https://www.github.com/ SohamSahaNeuroscience/Covid-19_Eprotein_ models
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