Computational Study on the Function of Palmitoylation on the Envelope Protein in SARS-CoV-2

Abstract

SARS-CoV-2 that caused COVID-19 has spread since the end of 2019. Its major effects resulted in over four million deaths around the whole world by August 2021. Therefore, understanding virulence mechanisms is important to prevent future outbreaks and for COVID-19 drug development. The envelope (E) protein is an important structural protein, affecting virus assembly and budding. The E protein pentamer is a viroporin, serving as an ion transferring channel in cells. In this work, we applied molecular dynamic simulations and topological and electrostatic analyses to study the effects of palmitoylation on the E protein pentamer. The results indicate that the cation transferring direction is more from the lumen to the cytosol. The structure of the palmitoylated E protein pentamer is more stable while the loss of palmitoylation caused the pore radius to reduce and even collapse. The electrostatic forces on the two sides of the palmitoylated E protein pentamer are more beneficial to attract cations in the lumen and to release cations into the cytosol. The results indicate the importance of palmitoylation, which can help the drug design for the treatment of COVID-19.

Structure and dynamics of the SARS‐CoV‐2 envelope protein monomer

“…Root mean square deviations of the TM helix heavy atom positions between the available NMR models is above 6 Å 51,57 . Simulations performed by other laboratories reveal low stability of the pentameric models and frequent collapses of the pore 76,86–88 . Thus, behavior of the pentameric envelope protein deserves a very careful consideration.…”

“…51,57 Simulations performed by other laboratories reveal low stability of the pentameric models and frequent collapses of the pore. 76,[86][87][88] Thus, behavior of the pentameric envelope protein deserves a very careful consideration. Perhaps, simulation of the pentamer assembly process starting from monomers or oligomers 89 would prove helpful in arriving at a satisfactory model.…”

Viroporins: Structure, function, and their role in the life cycle of SARS-CoV-2

“…Surprisingly, in E and N protein co-expression experiments, palmitoylation of SARS-CoV E protein had no effect on its association with N protein or subsequent VLP production, and thus is not required for SARS-CoV assembly, and the contribution of E protein palmitoylation to virus packaging and VLP production appear independent form each other ( Tseng, Wang et al 2014 ). Molecular dynamics simulations of SARS CoV-2 E protein indicate that the stability of the palmitoylated E protein structure is increased, while loss of palmitoylation causes reduction of the pore radius, and even collapse of the pore.”( Sun, Karki et al 2021 ).…”

Methodology-Centered Review of Molecular Modeling, Simulation, and Prediction of SARS-CoV-2

“…Their results indicated that the structure of the palmitoylated E protein pentamer was more stable while the loss of palmitoylation caused the pore radius reduced and even collapsed, which might help the drug design for the treatment of COVID-19. 169 …”