FIGHTING DISEASE THREATS
STOPPING A GLOBAL KILLER
Researchers in the Institute for Biomedical Sciences are teaming up to defeat a menacing disease that has taken a deadly toll across the globe – COVID-19.
People have long wondered what the next dangerous pathogen would be.
While humans have encountered some deadly viruses over the centuries such as influenza, Ebola, smallpox, SARS, MERS and HIV, there are inevitably new, life-threatening diseases out there waiting to emerge. Experts have agreed that it wasn’t a question of if – but when – another lethal infectious agent would occur and speculated if the world would be ready to fight it. Sadly, the answer is no.
As the new year began, coronavirus disease 2019 (COVID-19), a novel, highly contagious disease that was first reported in Wuhan, China, caught the world off guard, rapidly spreading across the globe and causing an unprecedented public health crisis. In only months, COVID-19, which is caused by a new virus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), infected millions of people worldwide and killed nearly 205,000 (as of April 29, 2020).
The ominous disease was declared a pandemic by the World Health Organization because of its alarming levels of spread, severity and infection, and the United States soon had the highest number of confirmed cases and deaths in the world. But the threat isn’t over. COVID-19 is still lurking and waiting to infect new victims, and there are no approved therapeutics and vaccines in sight.
There’s an urgent need to prevent and treat COVID-19, and six scientists in the Institute for Biomedical Sciences have teamed up to develop effective therapeutics and vaccines, combining their expertise in life-threatening, infectious diseases and inflammatory diseases to get the crucial task done.
The scientific SWAT team – with experts on Ebola virus, influenza viruses, respiratory syncytial viruses and other infectious and inflammatory diseases – is working around the clock to conquer one of the most treacherous diseases in human history.
“We’re taking advantage of the strategies we have developed in the past studying other life-threatening viruses and using the lessons we have learned to develop effective therapeutics for fighting COVID-19,” said Jian-Dong Li, director of the Institute for Biomedical Sciences and a Georgia Research Alliance Eminent Scholar in Inflammation and Immunity at Georgia State. “Also, while developing therapeutics is urgently needed, vaccines are absolutely required for preventing people from getting this disease. Because of the time that vaccine development takes, our scientists have already started to take action to develop effective vaccines. Our strengths, experience and past lessons put us in a better position to solve this global crisis.”
Although the work of the institute’s scientists has focused on understanding and developing therapeutics for other pathogens, their approaches are likely applicable to COVID-19. Three researchers are working to develop treatments for COVID-19.
Christopher Basler, professor and director of the Center for Microbial Pathogenesis, and also a Georgia Research Alliance Eminent Scholar in Microbial Pathogenesis, is seeking to identify candidate therapeutics that inhibit viral genome replication of SARS-CoV-2. He will apply lessons and strategies learned from his work with Ebola virus to inhibit SARS-CoV-2 using a variety of approaches. Basler is also collaborating with clinical investigators to better understand the progression of COVID-19 in human patients.
In previous work, the world-renowned virologist found that a small molecule compound that inhibits Ebola virus also had activity in cell culture against Middle Eastern respiratory syndrome (MERS), which is similar to COVID-19 and caused sporadic disease in the Middle East for several years.
“We prevented growth of the virus outside the context of an animal,” Basler said. “You would expect that what combats and inhibits one coronavirus may act against another coronavirus.”
For his laboratory studies, Basler will collaborate with scientists at Sanford Burnham Prebys Medical Discovery Institute in California and several other leading institutions.
Richard Plemper, a Distinguished University Professor, has previously developed effective therapeutics to control influenza by inducing genetic error catastrophe in the virus, leading to the virus’ death. A compound developed in collaboration with Emory Institute for Drug Development has been chosen as a therapeutic candidate for clinical testing against COVID-19. Plemper now applies his ferret and human airway epithelium organoid infection models to SARS-CoV-2 and will conduct drug screening studies to determine dosing and efficacy.
“The work from Dr. Basler and Dr. Plemper’s laboratories certainly holds some promise,” Li said.
Still, traditional drug development is time-consuming and expensive. In contrast, drug repurposing, which finds new uses for existing drugs, has been encouraging for treating difficult diseases because it’s safe, takes a shorter amount of time and costs less money.
Li will use the drug repurposing strategy to develop anti-inflammatory agents for controlling overactive inflammation in COVID-19 patients.
“Overactive inflammation is the hallmark of COVID-19 that is responsible for a patient’s death,” Li said. “Proper inflammation is critical for host defense and virus clearance, but if it’s uncontrolled, it will lead to tissue damage and ultimately lead to respiratory failure and death. Anti-inflammatory drugs that have been developed using the traditional strategy turn out to be less rewarding because while these drugs do have some therapeutic effect, they also have some significant side effects that prevent them from being used in the clinic. The advantage of drug repurposing is that it’s already a drug. It’s safe and available.”
To effectively treat COVID-19, therapeutics are needed that both suppress the virus and reduce inflammation the virus has caused. A combination therapy of antiviral and anti-inflammatory drugs would be ideal. Li’s goal is to identify an existing anti-inflammatory drug that can be paired with antiviral therapeutics developed by his colleagues.
“This would be a tremendous cocktail for fighting COVID-19,” Li said. “This combination therapy would satisfy both essential needs.”
For long-term success against COVID-19, vaccines are critical for blocking new viral infections. Two researchers in the institute are working to create vaccines to protect against SARS-CoV-2.
Dr. JoAnn Tufariello, an infectious diseases physician scientist in the Center for Microbial Pathogenesis, will develop a vaccine with the goal of inducing rapid immunity against SARS-CoV-2, a critical need. This work builds upon a previously developed vaccine platform that proved to induce rapid protection against the Ebola virus.
In addition, limited viral strains have been reported to be responsible for COVID-19 diseases, but it’s unclear whether new strains will occur. A universal vaccine is needed to protect against all strains of the virus.
Baozhong Wang, associate professor, will develop a universal vaccine for SARS-CoV-2 using an innovative strategy he has created for universal flu vaccines. Wang has already developed a powerful research strategy for an effective, universal influenza vaccine with double-layered protein nanoparticles. He will use this layered nanoparticle vaccine platform to develop a universal vaccine for SARS-CoV-2.
“Scientists do not know if SARS-CoV-2 will disappear soon like SARS-CoV or MERS-CoV or will evolve into a yearly visiting disease like seasonal influenza,” Wang said. “However, no matter what it may evolve into, an effective vaccine can be the terminal countermeasure to hurdle this infectious disease.”
It’s unclear why some people are more susceptible to COVID-19 than others.
Andrew Gewirtz, a Distinguished University Professor, plans to investigate the observation that gastrointestinal symptoms are an early predictor of severe, life-threatening disease in response to COVID-19 infection. He will study if such intestinal symptoms
of COVID-19 infection are influenced by the gut microbiome, which is the collection of microorganisms that live in the digestive tract.
“There is evidence that the intestine is important for disease severity and spread of the virus, so we hope to learn if microbiota influences it,” Gewirtz said.
He will analyze the microbiome in fecal samples from suspected and confirmed COVID-19 patients, including those with severe, mild or long-lasting disease. This will allow him to determine the role of gut microbiota in mediating susceptibility and the severity of disease and predicting the clinical outcomes of disease.