Whether it’s SARS, MERS, Ebola, or this new coronavirus, these viruses have led to outbreaks that have caught humans off guard and caused tremendous pain. Although the outbreak is not yet over, laboratories are under construction to predict the next large-scale outbreak.
Since the outbreak of SARS in 2003, scientists have begun to pay more and more attention to coronaviruses, which are of a large variety of viruses and can be transmitted across different species – searching for “coronaviruses” on GenBank, a public genome library, resulting in more than 35,000 results, including from alpacas, hedgehogs, Coronaviruses in species such as beluga whales;
Bats receive the most attention among all possible hosts because they have evolved a unique ability to coexist with viruses, including those that are particularly likely to be transmitted to humans. THE SARS VIRUS, MERS VIRUS, MARBURG VIRUS, NIPA VIRUS, EBOLA VIRUS, AND THIS NEW CORONAVIRUS ARE MOST LIKELY CAUSED BY BATS.
Michael Letko has sequenced samples from bats since he was a Ph.D., and most of the genomes he collected are related to coronaviruses.
In 2007, Chinese researchers took blood samples from bats and discovered a virus called HKU4-Cov, which exploded in Saudi Arabia five years later, and when scientists sequenced the MERS virus, it found that the protein sequence of the virus was almost identical to that of HKU4-Cov. Michael Letko says:
If the data had been available before the MERS outbreak, scientists would have known in time how the MERS virus spreads and what treatments might be effective.
Michael Letko added that he wanted to try to provide such data and decided to set up a platform for experimental testing of the coronavirus genome collected around the world. He believes that if people want to figure out where the next large-scale outbreak will come from, coronaviruses are a good starting point because they are ubiquitous and can infect humans across species barriers. If people can understand the differences between these viruses, they can create a predictive engine to predict which viruses are most likely to appear in the population.
Electric mirror photos of the new coronavirus, pictured from the China Center for Disease Control and Prevention
Michael Letko’s idea seems to be an important help to people in outbreak prevention and control, but the plan is difficult to implement.
First, it is difficult to isolate the virus from a sample in the wild. The cells cultured in the lab, unlike those in the wild animals, often fail to get the material needed for virus growth from nature. In other words, scientists can’t keep the virus alive long enough to experiment. Second, it is expensive to reverse-engineer viruses from sequences, and coronaviruses have the largest number of genomes of any RNA virus, costing $15,000 to do just one.
Coronary viruses are so named because the protrusion proteins on their surface appear to look like crowns when enlarged. These protrusion proteins help the virus enter the host cell and then replicate and spread it in the host cell. The nuances of the shape of the protrusion determine what kind of cells the virus can infect — that’s what Michael Letko’s research is focused on.
Throughout 2018, Michael Letko is committed to building a synthetic virus particle system. Through this system, he can replace the virus’s RBD (receptor binding domain) and then learn which RBD sequences can access the receptor and enter the cell through the hamster experiment. In January 2019, Michael Letko began further experiments in which he would be able to copy and paste sequences into hamster cells into synthetic virus particles, expose them to human receptor cells, and sort infection potential.
In addition to known coronaviruses, such as SARS, Michael Letko also collected unknown strains from Chinese horseshoe bats. But testing and validating results will take time, and he expects the system to be perfected in a few months – by the end of 2019, he will be able to extract a sequence from a gene bank and get experimental data on the virus in a week’ time, such as whether it can infect human cells and what cells it can infect. and to what extent it can penetrate cells.
In December 2019, Michael Letko began printing out the results of the past two years of labor and is preparing to submit these reports to a journal for peer review. Subsequently, the outbreak of New Coronary Pneumonia in Wuhan, a new type of coronavirus, has never been found in humans before.
Researchers isolate new coronavirus
On January 10th Chinese scientists published the genome of the virus. Michael Letko downloaded the genome and located the RBD sequence. Through experiments, he found that the new coronavirus is very similar to the SARS virus, both through the receptor ACE2 infection of human cells, which is common in lung cells. Mild cases can show symptoms of coughing, and severely can cause breathing difficulties.
The time taken from the sequence release to Michael Letko’s identification of the virus’s attack location is 7 days. In response, Kristian G. Andersen, an infectious disease geneticist at the Scripps Research Institute, said, “It’s incredibly fast.” “
Kristian G. Andersen himself was not involved in the study, but his lab used DNA data to track the evolution of the Ebola virus, the Zika virus and the new coronavirus outbreak. Michael Letko’s efforts could be very helpful at the moment of the outbreak, he added.
Because vaccines and new treatments are months away from human trials, much of the hope of fighting the virus rests largely on existing drugs. Through Michael Letko’s experiment, scientists were able to understand how the virus binds to human cells, and thus figure out how to prevent the virus from entering the cells.
Although the outbreak has not subsided, Michael Letko is already preparing for the next possible outbreak — he wants to gather more information about animal-induced viral infections and find out which viruses can infect humans. “With this data, we can predict what will be a great threat to the future of humanity,” says Michael Letko. “
In the coming months, Michael Letko will set up his own lab at Washington State University. There, he plans to expand the project’s research beyond different coronaviruses, but also proteins that are key to the virus entering cells and avoiding the human immune system.
Based on the results of these experiments, Michael Letko will build a coronavirus profiling system, as well as an information database of protein interactions, that scientists can use to quickly label new viruses that may have pandemic potential.
Michael Letko says:
In order to collect and generate all this data, we need to spend a lot of manpower and effort. But it’s worth it.