Machine-learning a virus assembly fitness landscape

Two facts about simple viruses have been known for a long time. Firstly, that genetic economy leads to the use of symmetry, such that virus capsids aremostly icosahedral or helical. Secondly, packaging signals, that is secondary structure features in the viral RNA, are often required for encapsidation inviruses with single-stranded genomes. Examples are the origin of assembly sequence in Tobacco Mosaic virus, the psi element in HIV and the TR sequence in MS2. This is an evolutionary advantage, as it ensures vRNA-specific encapsidation and can increase assembly efficiency through a cooperative role of the RNA, which acts as a nucleation site. More recently, it has been shown that taken together, these two facts suggest that there could be more than one packaging signal, with multiple signalsin fact dispersed throughout the genome. This is because the capsid is symmetric, and the packaging signal mechanism functions via interaction betweenviral RNA and the coat protein (CP). In several cases, this RNA-CP interaction leads to a conformational change in the CP, which only then makes it assembly competent (e.g.