Computational modelling of flavivirus dynamics: The ins and outs

Abstract

Enveloped viruses such as the flaviviruses represent a significant burden to human health around the world, with hundreds of millions of people each year affected by dengue alone. In an effort to improve our understanding of the molecular basis for the infective mechanisms of these viruses, extensive computational modelling approaches have been applied to elucidate their conformational dynamics. Multiscale protocols have been developed to simulate flavivirus envelopes in close accordance with biophysical data, in particular derived from cryo-electron microscopy, enabling high-resolution refinement of their structures and elucidation of the conformational changes associated with adaptation both to host environments and to immunological factors such as antibodies. Likewise, integrative modelling efforts combining data from biophysical experiments and from genome sequencing with chemical modification are providing unparalleled insights into the architecture of the previously unresolved nucleocapsid complex. Collectively, this work provides the basis for the future rational design of new antiviral therapeutics and vaccine development strategies targeting enveloped viruses.

Keywords: Coronavirus; Dengue; Enveloped virus; Molecular simulations; Multiscale modelling; Structural genomics; Zika.