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. Using the bioinformatics and structural modeling approach, we modeled 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-terminal regions. Incidentally, compared to spike proteins, E proteins demonstrate lower disparity and mutability among the isolated sequences. Using homology modeling, we found that the most favorable structure could function as a gated proton channel. 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. 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 proton channeling activity which may play a critical role in viral infection. In addition, it provides a structural basis and additional avenues for LAV development and generating therapeutic interventions against the virus. Significance Statement Structural modeling of the novel SARS-CoV-2 envelope protein (E-protein) demonstrating its possible proton channeling activity

Structural insight into the putative role of novel SARS CoV-2 E protein in viral infection: a potential target for LAV development and therapeutic strategies