In a new study published in the journal Science, researchers outline their work that could be considered a major step towards the development of a viable vaccine for the 2019 novel coronavirus. The work was deemed so pertinent that the journal Science expedited its review process for the study manuscript.
The team of scientists from The University of Texas (UT) at Austin and the National Institutes of Health, led by Jason McLellan, Associate Professor at UT Austin, have studied other coronaviruses in the past, including both the SARS-CoV and the MERS-CoV.
The fungi, bacteria and parasites that constantly invade the human body all express individual proteins that are required to create infection and effectively "dodge" the human immune system.
McLellan's lab explores the concept of structure-based vaccine design by studying these proteins. Their work is summarized eloquently on the UT Austin site: "We seek to obtain structural information on [these] proteins and their interactions with host macromolecules and translate this knowledge into the rational development of therapeutic interventions such as small-molecule inhibitors, protective antibodies and stabilized vaccine immunogens."
The novel coronavirus (2019-nCoV), first reported from Wuhan, China, on 31 December, has been a global focus over recent weeks as it was declared a global emergency by the World Health Organization.
You can learn more about the virus and what we know so far by watching the video below:
Taken from the World Health Organization.
Initially, the virus was deemed to be severe cases of pneumonia; however, it soon became clear that it is in fact a coronavirus. Having worked with coronaviruses extensively, this information immediately sparked McLellan and team's attention: "As soon as we knew this was a coronavirus, we felt we had to jump at it," McLellan said.
Coronavirus spike proteins
McLellan and team's previous research has revolved around developing analytical methods to study coronavirus spike proteins. This spike protein is a "multifunctional molecular machine" that facilitates coronavirus entry into the cells of the host. Understanding more about this molecular machinery can enhance vaccine and anti-viral drug development efforts.
The scientists were successful in locking the coronavirus spike proteins into a specific shape that enabled their analysis. In the latest study published in Science, they created the first 3D atomic scale map of the 2019-nCov spike protein using cryogenic electron microscopy (cryo-EM).
No time to waste – expediting review processes
Nianshuang Wang, research associate, and other lab members work in the lab. Monday Feb. 17, 2020 at The University of Texas at Austin.
After receiving the genome sequence of the virus, the scientists, including the study's co-first authors, Ph.D. student Daniel Wrapp and research associate Nianshuang Wang, both at UT Austin, had designed and created samples of the stabilized spike protein.
Another 12 days or so later and the molecular structure of the spike protein was established, and a manuscript presented to Science.
The journal Science accelerated the peer review process based on the time-sensitive nature of the study and the continual spread of 2019-nCov.
Small spike, mighty vaccine?
The scientists attribute their successful (and speedy!) feat to the use of the cryo-EM technology made available to them via the Sauer Laboratory for Structural Biology: "We ended up being the first ones in part due to the infrastructure at the Sauer Lab," McLellan said. "It highlights the importance of funding basic research facilities."
Cryo-EM is certainly making a name for itself as a rising, if not already established, star in the structural biologist's toolbox after winning the 2017 Nobel Prize for Chemistry.
Using this methodology, McLellan et al obtained a structure of the extracellular portion of the spike protein of the 2019-nCov. It's small, but it's mighty – enough to provoke an immune response in a host, and therefore potentially function as a vaccine.
Their next step is to use the molecule as a "probe" of sorts to collect and isolate antibodies that are produced by previously infected patients that are now recovered. It's possible that such antibodies could be utilized in patient's that have been recently exposed to the virus, such as health care and other professionals on the front-line of the infection management.
You can learn more about the cryo-EM technique and the 2019-nCov below:
Reference: Wrapp et al. (2020). Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. DOI: 10.1126/science.abb2507