The history of mankind is marked with life-threatening epidemics and pandemics. For the last several hundred years, deadly strains of influenza virus have circled the globe every year and taken the lives of millions. Approximately three outbreaks each century are classified as pandemics, some more lethal than others. The Spanish flu, raging between 1918 and 1920, surpassed the deadliness of both the First and Second World Wars combined. Research on pandemic outbreaks aims to answer several basic questions: the cause, spread, prevention and treatment. The path to the answers is complex and requires an interdisciplinary approach, including mathematical modeling, structural biology, drug and vaccine development, as well as insights in human behavior and economics. Despite impressive findings and accumulated know-how, the world was poorly prepared for the current coronavirus outbreak. Why?
Figure 1. Schematic representation of a coronavirus.
Viruses are bags of genetic material, capable of reproducing when exposed to a favorable environment. Errors during reproduction cause random mutations, which can lead to two unfavorable scenarios: a human virus can become more dangerous, or a highly dangerous virus jumps from an animal host to a human. This latter scenario is what happened with SARS-CoV-2, the virus causing the current pandemic. The ancestor of this virus is native to bats. After ill-fated genetic changes, the new virus found an accommodating home in humans whose immune system is poorly prepared for the intruder. The virus spreads fast, aided by a high reproduction number and a globalized world. There is currently neither a cure nor a vaccine.
One of the steps towards the cure and vaccine involves knowing the genetic information of a virus and the atomic structures of the proteins involved in its cell entry, reproduction and exit. This information can help answer three crucial questions: how a virus can be detected, how it attaches to a human cell and how this interaction can be blocked, and what drugs decrease its reproduction and exit from the cell. Many research groups worldwide are working on these questions with great urgency.
Macromolecular crystallography and cryo-electron microscopy (cryo-EM) are used for examining viral proteins down to the atomic level. This information shortens the drug development, as it identifies the sites of interaction between the virus and the host cell or the catalytic sites of enzymes involved in the life cycle of the virus. Analysis of the genetic material of a virus makes it easier to prepare protein samples for structural work. It is also essential for establishing test kits for the virus. These are usually based on detecting viral sequences in human cells.
Although virus outbreaks are driven by random processes, there are tools that can improve the way we predict the outbreaks. Examples include the observation of viruses circulating in animals, particularly in birds and bats, but also mathematical simulations of viral spread. As these mathematical approaches are based on understanding of the movements of people and their interactions, their accuracy relates to the quality of collected data. In a recent citizen-science experiment, Dr. Hannah Fry from the University College London recruited almost 30 000 participants and monitored their interactions using a phone app. The experiment was broadcast as a documentary film in 2018, while the mathematical model behind the film was published in the journal of Epidemics.
The World Health Organization is closely monitoring the progress on the research of the coronavirus disease, and it summarizes the newest scientific findings in a curated database. The database is updated daily, and it feeds from bibliographic resources, tables of contents of relevant journals, and the addition of other relevant scientific articles. Elsevier is taking similar steps, and it offers an open access online platform that contains expert information for the research and health community on novel coronavirus. Although there are no officially approved drugs against the disease, pharmaceutical companies are working on several candidates that have entered in clinical trials to treat and prevent COVID-19 in a shorter term.
Figure 2. A surface representation of SARS-CoV-2 protease shows the deep active site where a peptidyl inhibitor (shown in green sticks) binds.
During this pandemic, both X-ray crystallography and cryo-electron microscopy (cryo-EM) have demonstrated their merit. In only a few months, these techniques have yielded accurate structures of a series of SARS-CoV-2 proteins. This unprecedented speed relied on technological progess. RNA sequencing combined with gene synthesis dramatically decreased the time until a protein could be produced for structural studies. Data collection protocols have been improved, sample throughput has increased, and data processing software has become more powerful. One of the largest European synchrotron sources, Diamond Light Source (DLS), is dedicating a great portion of their resources to push research on SARS-CoV-2 forward. DLS’ official coronavisrus-dedicated website explains the role of structural biology in the research of human health in a series of texts suitable for scientists, the public and the media.
Tests for viruses usually rely on detecting the genetic material within the virus using the Polymerase Chain Reaction (PRC). In the case of SARS-CoV-2, the test starts by turning its genome, which is made of single-stranded RNA, into DNA using an enzyme reverse transcriptase. The tiny amounts of new DNA are then multiplied and exposed to a fluorescent dye that glows in the presence of DNA. Although commonly used, this method suffers one drawback: it requires the virus to be present in the host organism.
Serological tests can be used to look for specific antibodies that the body has produced to fight the virus, even after the immune system has cleared the virus. Although many labs are racing to develop antibody tests, these need to be carefully validated to be sure they react reliably, but only to antibodies against the novel virus. According to Science magazine, Singapore is currently testing an experimental antibody test against SARS-CoV-2.
Considering that the use of isolation and quarantine to prevent pandemic crisis date back to 1377 (Dubrovnik, Croatia), one could imagine that mankind has mastered the skills of a lockdown. However, as the modern world is witnessing research facilities being shut down and infrastructure being reduced to essential needs, our (complex) daily lives are facing many challenges: lack or delay in technical support, distance learning, constant worry, or combining home office with childcare. At DECTRIS, we are facing similar problems, and although we cannot provide a ready-made solution, we are dedicated to collecting tips and advice from our colleagues and beyond.
Whether you are looking for information or are willing to convey your knowledge to those in need, consider online platforms for communication. Here we present a few ideas.
The platform Skype a scientist gathers enthusiastic scientists willing to share their expertise and knowledge-seeking students. The main point: this program allows us to reach students from all over the world without having to leave the lab!
Carefully curated scientific blogs can be an excellent source of information, including video tutorials, open access papers and answers to frequently asked questions. For example, all those interested in small angle X-ray scattering (SAXS) techniques may benefit from Looking at nothing, a blog kept by Dr. Brian Pauw. He is a SAXS expert who develops advanced applied methodologies for small-angle scattering, and he works as a researcher at the Bundesanstalt für Materialforschung und -prüfung BAM in Germany.
International Centre for Diffraction Data is the place to start. Since 1999, ICDD has hosted 16 Pharmaceutical Powder X-ray Diffraction meetings. The abstracts from symposia are publicly available as well as the presentations, except for the most recent event.
To assist the many students, faculty, and researchers who are working and studying remotely during the COVID-19 pandemic, Annual Reviews have made their journals freely available until Thursday April 30, 2020.
Not many of us are experts in the home office field, particularly when exposed to extreme conditions such as a viral pandemic. At DECTRIS, we are committed to exploring and utilizing digital technologies to keep the communications and knowledge-sharing processes working. Our tips and strategies include advice on how to make the home office work and a suggestion for a podcast tackling an uncomfortable topic: isolation.
More helpful links:
Figure 3. Isolation during the Great Plague in the year 1665: Isaac Newton’s annus mirabilis has yielded scientific findings in the fields of calculus, gravity and optics. To our knowledge, contributions to teaching, homework or childcare have not been published.
Our team of scientists has been preparing application- and technology-specific content for a while now. Application notes, white papers and webinars address the use and performance of HPC detectors in powder X-ray diffraction, macromolecular crystallography and Laue diffraction.
Whether you have a technical question about your HPC detector, or you would like to discuss your application, our team of scientists and technical staff are here to support you. Feel free to contact our support at firstname.lastname@example.org. Most importantly, take care! We are looking forward to seeing you in person soon.