Just 10 months ago most of us had never heard of Covid-19 – now it is a term we refer to several times a day as we learn to live and work alongside this pandemic. Six months ago, when we entered our first lockdowns, little was known about this particular virus, how it worked to infect us and how it spreads. However, in just over six months scientists all over the globe, often working in collaboration with the UK’s Synchrotron, Diamond Light Source, have made huge progress in understanding how Covid-19 operates and as a result, they have opened the doors to real possibilities of solutions and therapies.
A new video animation has been released showing how the SARS-CoV-2 (or Covid-19) virus infection mechanism works at the cellular level. The intention is to inform and share with the public the knowledge that scientists working with Diamond have uncovered how the virus replicates itself. The genome replication, assembly and egress of the virus is a multistage process that is critically important as it bears the means of medical intervention to stop infection.
This is the first time the virus has been depicted in this way, showing in detail how the virus infection mechanism operates based on our understanding so far. The animation is entirely based on the work achieved at Diamond using both Cryo-EM and X-ray Crystallography:
Professor David Stuart, Life Sciences Director at Diamond and Joint head of Structural Biology at the University of Oxford, said: At the beginning of the pandemic we didn’t know exactly what the virus looked like but in record time, it has been dissected in great detail. This is really important because by understanding how it works and mapping out the infection mechanism, we are much further closer to our goal of finding therapies. Our hope is that this animation will help articulate achievements so far.
The animation was created by combining a set of images achieved via various scientific imaging techniques from synchrotron-based crystallography and imaging to high resolution Cryo-electron microscopy to depict the entire SARS-CoV-2 infected cell. This unique approach gives a holistic view of SARS-CoV-2 infection, from the whole cell to individual molecules, revealing unseen pathways of the virus assembly and egress, and the cellular structural changes caused by the virus. Further development in the area of labelling individual viral and relevant host proteins involved in the process will be essential to allow a correlative structural analysis at the molecular level.
Prof. Stuart added that in response to the outbreak of Covid-19 efforts from scientists around the world have yielded a great deal of knowledge on the etiological agent. "Structural understanding of the viral components is key to the discovery of therapeutics and so far work has concentrated on virial spikes, main protease, RNA polymerase and other non-structure proteins, as well as spike interactions with host receptor ACE2 and neutralising antibodies, using a range of tools from synchrotron based X-ray crystallography to cryoEM and cryoET. These latter two techniques are essential for in vitro and in situ study in the context a virion. However, all these techniques will be important in tackling the challenges that lie ahead with the remaining viral components, which are small, flexible and heterogeneous, and some are even membrane bound, but they are pivotal in understanding the entire virus architecture and its genome organisation."
The many Covid-19 related research projects that Diamond is working on are a great demonstration of the powerful synergy between Diamond and its neighbouring research institutes, the Research Complex at Harwell and the Rosalind Franklin Institute. Diamond is working with its valued users and many partners to look at the fundamental interactions of the virus, from which it is hoped new therapies can be developed. It is also enabling the study of how existing drugs, that have already been tested and approved for other diseases, can be repurposed and used to treat patients. The array of specialised tools and instruments at Diamond, along with the scientific and technical expertise of its staff, allow for many different techniques to be used, from looking at the structure of the virus and fitting drugs into it, like a tiny jigsaw puzzle, to taking direct images of the virus without its infectious component, making it possible to see how it interacts with drugs.