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How to disassemble a virus capsid: a computacional approach
Publication . Piedade, Claudio Alexandre; Ferreira, António Eduardo do Nascimento, 1964-
Viruses are one of the main subjects of study in science due to the amount of diseases and deaths they cause, not only in humans, but also in other organisms, such as plants, other mammals, insects and microorganisms. This raises the need to understand the mechanisms of host infection. Capsids surround the genetic information of viruses and many experimental and theoretical studies have been done to study the icosahedral virus capsid assembly, but very few have focused on the disassembly process. These rare studies point to the loss of a triangle-shaped trimer as the first step of disassembly, or to the loss of a pentagon-shaped pentadecamer (15-mer). Also, no study was found that approached the problem of disassembling virus through a 60-subunit model using combinatorial geometry and symmetry groups. In this work, we tried to predict the sequence of subunit loss from the virus capsids using a combinatorial and geometric approach, taking into account the equivalence of subunit configuration and using cyclical permutations of the Deltoidal Hexecontahedron symmetry group, applied on a binary vector. The aim of this study was to assess whether there was a similar process of capsid disassembly throughout different viruses’ families and, if not, try to find a pattern of disassembly characteristic of a given family. Using T = 1 viruses’ capsids, we analysed 51 known structures that were subdivided into 14 groups and predicted the sequence of the loss of up to 5 subunits. The energy of the different capsid configurations was estimated by three different heuristics, all based only on the number of weak inter-subunit contacts. Our results show a prevalence on the lost of a triangle-shaped trimer of subunits in several of the groups identified, mainly those comprising Parvoviruses, Circoviruses, Birnaviruses and Hepatitis E Viruses. Densoviruses (a parvovirus) also, in general, loose a square-shaped tetramer while Human Adenoviruses Pt-Dd loose a pentagon-shaped pentamer. All these viruses, except for Human Adenoviruses Pt-Dd, loose a right-trapezium or a scalene-trapezium-shaped pentamer, built by the lost of a triangular trimer and two adjacent subunits. This work shows that there is a main disassembly pathway, through the removal of a triangle trimer, although it can not be generalized to all icosahedral viruses. These predictions have a very low dependency on the heuristical measure of total energy used. This triangular trimer might be an interesting target for novel antiviral drugs, by interfering with the capsid disassembly.
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Fundação para a Ciência e a Tecnologia
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3599-PPCDT
Número da atribuição
RECI/BBB-BEP/0104/2012