Understanding the virus that causes COVID-19
Dr. Liang asks two questions in his funding proposal: how did coronaviruses transmit from animals into humans and what makes SARS-CoV-2 so pathogenic and lethal?
He points to two recent diseases with global impact that were also caused by a spillover of animal coronaviruses into the human population: severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). Both had high fatality rates of 11% and 35% respectively. In comparison, COVID-19 has a lower fatality rate but a higher rate of infection.
“If we do not understand how this has happened, we will never be able to prevent this type of crisis, which surely will happen again in the future,” states Dr. Liang.
One direction he and his team are pursuing is to understand how SARS-CoV-2 can suppress our interferon response. Interferons are cytokines that are part of the body’s natural defenses and keep viruses that enter the body from multiplying. If a virus can somehow suppress interferon production, it can replicate very fast and cause damage to the body’s organs and tissues.
Another aspect they are investigating is how the signature spike-shaped proteins located on the surface of the SARS-CoV-2 particle, bind to a cell surface protein called angiotensin converting enzyme 2 (ACE2). When the spike protein binds with the human ACE2, SARS-CoV-2 can enter cells and then start replicating. Dr. Liang’s team is trying to understand how this spike protein recognizes ACE2 proteins and are developing methods to monitor this interaction. Their primary goal is to then screen for a drug compound that can block this interaction.
When SARS-CoV-2 infects humans, antibodies produced by our immune system recognize and target the spike protein in order to kill the virus. Dr. Liang’s team will use their findings to look at serum samples from COVID-19 patients and see which among them have a high level of these neutralizing antibodies. “The important thing is that if we identify the serum or plasma that has a high level of SARS-CoV-2 neutralizing antibodies, then those plasma can be used to treat COVID-19 patients who are very, very ill. This has been shown effective in some studies and is quite exciting.”
Until researchers develop a vaccine and effective treatments, Dr. Liang stresses that self-isolation remains the best way to prevent the spread of the virus. “We must continue to do what we're doing now to slow down the transmission so that those people who are very, very ill can be treated and won’t die, and so that the hospitals won't be overwhelmed.”
Dr. Liang hopes to generate data from his research project as soon as possible, potentially within the next six months. Looking to the future, he states, “When we have a drug that can cure patients, things will change, people won't be so worried anymore, like any other illness.”