Identifying crucial E-protein residues responsible for unusual stability of Zika virus envelope

Biophys J. 2021 Aug 11:S0006-3495(21)00657-3. doi: 10.1016/j.bpj.2021.08.011. Online ahead of print.ABSTRACTOutbreak of zika virus (ZIKV) infections in 2015-16 that caused microcephaly and other congenital abnormalities in newborns prompted intense research across the globe. These studies have suggested that ZIKV can sustain high temperatures and harsh physiological conditions, unlike the other flaviviruses such as dengue virus (DENV). In contrast, recent cryo-EM studies have shown very similar architecture of the ZIKV and DENV envelopes that constitute the primary level of viral protection. Encouraged by these findings, here we attempt to identify the crucial protein residues that make the ZIKV envelope so robust by employing coarse-grained and all-atomic molecular dynamics simulations, and computational mutagenesis studies. In accordance with more recent cryo-EM findings, our simulation results exhibited stable ZIKV envelope protein shell both at 29o and 40°C, while the DENV2 shell loosened up significantly at 40°C. Subsequently, we simulated a series of ZIKV variants to identify the specific domain and residues involved in maintaining the structural integrity of the viral protein shell at high temperatures. Our results suggest that the DIII domain, more specifically, the CD- and FG-loop residues of the ZIKV protein shell play a crucial role in making the virus envelope thermostable by inducing strong raft-raft interactions. These findings can accelerate the rational desi...
Source: Biophysical Journal - Category: Physics Authors: Source Type: research