A Deep Look into the Biology and Evolution of COVID-19

UCTV roundtable explores the biological roots and spread of the global SARS-CoV-2 virus

Of the hundreds of coronaviruses known to exist, many are relatively harmless. Coronaviruses infect your nose, sinuses and upper throat but often result in nothing more than a common cold (see Know Your Coronaviruses).

So what makes the new SARS-CoV-2, the virus that has caused a global pandemic, such a society-altering threat?

Probing the biological basis of the novel virus and evolutionary spread of the COVID-19 disease it causes, a panel of UC San Diego biologists gathered for a special roundtable analysis hosted by UCTV. The program is available here: A Deep Look into the Biology and Evolution of COVID-19.

Roundtable moderator Suresh Subramani, distinguished professor emeritus in the Division of Biological Sciences and director of the Tata Institute for Genetics and Society, framed the program by highlighting three major areas of concern surrounding the pandemic and how it impacts our daily lives: the rapid spread of the virus over the past three months; the ominous morbidity and mortality rates of the disease, which threaten to overwhelm global health care systems; and the immense reservoir of carriers of the disease.

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“It is estimated that there may be tenfold more asymptomatic carriers of the disease, which means that there could be over seven-and-a-half million carriers worldwide,” said Subramani. “This is a disease that is spreading very rapidly across the globe, so these faculty are here to share their knowledge regarding the biology of the virus and why this pandemic has brought the world to its knees.”

Emily Troemel, a professor who studies host-pathogen interactions in the Section of Cell and Developmental Biology, kicked off the discussion by describing basic biological aspects of coronaviruses, including how health workers test for the presence of SARS-CoV-2 infection and facets scientists have learned about the virus’ genome.

Coronaviruses, as Troemel noted, feature RNA-based genomes, unlike most of life on the planet, which feature DNA genomes. RNA genomes in coronaviruses are positive-sense, which are similar to the cell’s own messenger RNA and allows these viruses to immediately hijack the protein synthesis machinery of host cells. This feature enables these viruses to quickly and effectively take over host cells and rapidly expand.

“Knowing that it has RNA in its genome helps us understand how we test for the presence of coronavirus,” said Troemel. “In addition, we are able to look at changes in the sequence in the viral genome and that’s enabling us to track the spread of this virus around the globe…. We can learn about how the biology of the virus is changing and how it may be altering the way it interacts with host cells, and also potentially different ways that we could treat it. It’s part of an amazing open science effort with an unprecedented level of information acquisition and information sharing among researchers.”

Matt Daugherty, an assistant professor in the Section of Molecular Biology, studies the evolutionary arms race that pits the immune systems of hosts on one hand and pathogens on the other. He covered aspects such as how SARS-CoV-2 and other viruses enter the human population and become pandemics; how SARS-CoV-2 relates to past and present epidemic viruses in the human population; and, based on what scientists have learned from other viruses, what we can expect in terms of long-term immunity and co-existence with SARS-CoV-2.

“We as a species are always being exposed to viruses,” Daugherty noted.

Since SARS-CoV-2 is so new, there are many key unknowns related to human immune defenses against it, Daugherty said. Even with coronaviruses that cause common colds, it’s unclear whether humans develop long-term immunity to these viruses or need to continually develop new immunities.

“One thing I take comfort in with all of these other viruses is knowing that we aren’t constantly dealing with influenza pandemics and other pandemic viruses, and that’s because of the largely effective role of our immune system in dealing with these viruses once the immune system has been prepared,” said Daugherty.

For a virus that originated in an animal species to successfully infect humans, it needs to adapt to a range of genetic differences between the original host species and humans. But effective vaccines can ultimately thwart such pathogens.

“We have really good ways of making effective vaccines, and the hope is that this will hold for SARS-CoV-2 as well,” said Daugherty. “I take some comfort in knowing that these types of pandemics do pass and we will get through this.”

Justin Meyer, an assistant professor in the Section of Ecology, Behavior and Evolution, discussed concepts related to science and society’s ability to predict future pandemics. These include variables that contribute to the spread of pathogens; the increased likelihood of future pandemics; and predictions for where the next pandemic is likely to occur.

Factors that boost the risk of pandemics include human exposure to pathogens through meat consumption and contact with wild animals, increased human encroachment in wild areas and the exotic animal trade. Increased urbanization—more people living in close proximity means more opportunities for viruses to spread—and the rising consequences of climate change, also increase pandemic risks.

“We’re augmenting the temperature of the earth and environments in a way that we’re making ourselves more susceptible to diseases,” said Meyer. “When we warm the earth, we create more habitats for mosquitoes that carry vectors like malaria by increasing their range. They can spread to new human populations..... By increasing temperatures, we’re increasing flooding and there are many pathogens that are waterborne, such as cholera, which we will be exposing more and more people to.”

During the roundtable discussion, Subramani prompted the scientists with a handful of questions, including: Since many coronaviruses are relatively harmless, what makes SARS-CoV-2 so damaging to the lungs? What is the appropriate vaccine target for SARS-CoV-2 and in what time frame—from validation to FDA approval—is a vaccine likely? Can we look to drug targets where vaccines have been developed for related viruses and would that timeline be the same? Is there any evidence that SARS-CoV-2 has a mutation rate that is extraordinarily high?