Prison for viruses
Hepatitis B virus locked in a DNA cell
Alexander Dubov, N+1
With the help of DNA origami, chemists have made capsules in which you can lock and neutralize the virus. These capsules are shells with octahedral or icosahedral geometry, the size and shape of the capsules can be selected depending on the type of virus. As scientists write in Nature Materials (Sigl et al. Programmable icosahedral shell system for virus trapping), they managed to show the effectiveness of the approach on hepatitis B virus and adenoassociated virus.
One of the promising universal ways to combat viral diseases is to lock and neutralize viral particles in capsules made of biopolymers. In order for this approach to work, the capsule, firstly, must be large enough (the necessary virus must fit in it), and secondly, there must be chemical groups on its inner surface that bind to the functional groups of the virus itself (and it is better to have several of them for a firm fixation). Most often, such capsules are made similar to protein viral capsids. However, macromolecular cells made of protein usually do not exceed one hundred nanometers in size, so they cannot be used for large viral particles and they are not suitable as a universal means of neutralizing viruses.
American and German chemists led by Hendrik Dietz from the Technical University of Munich proposed using shells made of DNA molecules instead of protein capsules to bind viruses. Thanks to DNA origami technology, it is possible to assemble rather large structures from nucleic acids, and change their geometry and the location of functional groups with high accuracy.
The authors of the work proposed to assemble capsules for viruses from triangular elements. As a prototype of such a shell, scientists used icosahedral viral capsids. Capsids are made up of capsomers – identical protein elements that are folded into pentagonal and hexagonal structures, and those, in turn, into a polyhedron with icosahedral symmetry. Depending on the size of the DNA molecule that makes up the virus, the number of capsomers in the capsid will also differ.
In order to use a similar geometric motif to create artificial capsules, scientists first assembled several types of pseudosymmetric triangles from DNA molecules. These elements can be bonded to each other on the selected sides, and polyhedra of various sizes and shapes can be assembled from them: from an octahedral shell with a size of 90 nanometers to a complex capsule with icosahedral symmetry, very close in shape to a sphere with a size of 300 nanometers. (The size of the cavity inside the largest capsule is 280 nanometers.) The shell of the minimum size consists of eight triangular elements, the maximum of 180. Their molecular weight, respectively, varies from 43 to 925 megadaltons. To increase the stability of the capsules under physiological conditions, after assembly they were additionally irradiated with ultraviolet light, resulting in the formation of additional covalent bonds between the faces.
Hepatitis B virus in octahedral and icosahedral DNA cells. Three–dimensional images d and e were obtained from cryo-electron microscopy data, f - from transmission electron microscopy data. Figure from the article by Sigl et al.
The possibility of binding viruses in these capsules was tested by scientists on particles of hepatitis B virus and adenoassociated virus. To lock the virus inside such a capsule, antibodies specific to the desired virus were attached to the desired areas of its inner surface. As a result, the virus bound to several elements of the capsule, as a result of which the cell actually slammed shut around it. Thanks to this, it was possible to inhibit the interaction of hepatitis B virus with the surface in vitro and neutralize the adenoassociated virus in human cells.
According to scientists, modern biotechnologies make it possible to produce such capsules quickly and in large quantities. These shells do not interact with protein and must be non-toxic, in addition, other functional groups can be attached to their surface using DNA origami.
The process of assembling icosahedral and spiral capsids in vivo can be observed using transmission electron microscopy. For example, American scientists have discovered that around the center of viral RNA, the capsid nucleus is first slowly built, after which the rest of the proteins are attached to it. Because of this, "multi-headed" particles and "overgrown" capsids are sometimes formed.
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