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Summer 2020

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Colorized scanning electron micrograph of an apoptotic cell (green) heavily infected with SARS-COV-2 virus particles (purple), isolated from a patient sample. Image captured and color-enhanced at the National Institute of Allergy and Infectious Diseases (NIAID) Integrated Research Facility (IRF) in Fort Detrick, Maryland. Photo courtesy NIAID

 

  1. Coronaviruses come from a large family. It includes four genera and many species that infect a variety of mammals and birds — and sometimes reptiles. There are seven coronaviruses known to infect humans. Four of these cause very mild respiratory symptoms. The other three — SARS-CoV, MERS-CoV, and SARS-CoV-2 — can create a more severe respiratory illness. SARS-CoV emerged in 2002 and was quickly contained. In contrast, MERS-CoV, which emerged in 2012, continues to cause human infections due to repeated animal-to-human transmissions. SARS-CoV-2, also commonly referred to as the novel coronavirus, causes the disease called COVID-19 and is at the heart of the current global pandemic. It emerged in December 2019, and most of the initial cases were associated with people who had visited a live animal market in Wuhan, China.
  2. Coronaviruses sometimes jump between host species. Coronaviruses usually circulate among a single type of animal, such as cats, pigs, and dogs. These relatively common coronavirus infections are not known to spread to humans. However, some coronaviruses — those with the ability to recognize similar host proteins on cell surfaces — can infect multiple hosts. This sometimes leads to spillover events. SARS-CoV, MERS-CoV, and SARS-CoV-2 all likely originated in bats. SARS-CoV and MERS-CoV made the leap to intermediate host species, such as Asian palm civets and dromedary camels, which then transmitted the viruses to humans. It remains unknown whether SARS-CoV-2 passed through an intermediate host.
  3. The genomes of the three coronaviruses known to cause severe illness in people have all been sequenced. In other words, scientists have figured out the order of the basic molecules, called nucleotides, that make up the RNA (ribonucleic acid) genome of each virus. SARS-CoV-2 was sequenced in January 2020. This is important because the genetic data give scientists an idea of the virus’s origin, how it jumped from animals to humans, and how it might evolve. It also helped scientists develop the test that identifies infected patients.
  4. SARS-CoV-2 has spread faster than SARS-CoV. Whether the virus gains entry into cells depends on the interaction between two proteins, one human (ACE2) and one viral (Spike). Once the virus enters the human body, Spike helps it dock on the outer surface of a human cell, and this connection point is where ACE2, a receptor protein, lies. The two proteins form a bridge that allows the virus to enter and infect the human cell. This bridge, or bond, is much stronger in SARS-CoV-2 than it is in SARS-CoV, which may allow the virus to recognize human cells more easily.
  5. Close contact with an infected individual poses the greatest risk for coronavirus infection and developing COVID-19. Infection with SARS-CoV-2 (as well as SARS-CoV and MERS-CoV) strongly resembles infection with other respiratory viruses, including influenza. As with most respiratory viruses, the people with the highest risk of contracting the novel coronavirus are those who provide care for individuals who are already sick. This includes close family members and especially health care workers.
  6. Most people fully recover from COVID-19. The vast majority of people who become infected with the SARS-CoV-2 virus and subsequently develop COVID-19 will experience mild to moderate symptoms such as fever, cough, congestion, muscle aches, and headache. A portion of those infected will develop a more severe and sometimes life-threatening respiratory disease. The elderly and people who have underlying health conditions, such as heart disease, diabetes, or a compromised immune system, are the most at risk for this complication. Severe cases of COVID-19 have occurred in people who do not fall into these high-risk groups, but the reasons remain unclear.
  7. There are no approved drugs or vaccines for fighting human coronavirus infection. Unlike antibiotic drugs that can be used to treat a broad spectrum of bacterial infections, antiviral drugs tend to be highly specific for particular virus families. Coronaviruses are RNA viruses, a large group that includes influenza virus, hepatitis C virus, human immunodeficiency virus (HIV-1), rhinovirus, and Ebola virus. Viruses in this group carry their genomes as RNA rather than DNA. Certain broad-spectrum antiviral drugs can target a wider range of RNA viruses, but coronaviruses have natural resistance to many of them. Vaccines, on the other hand, are usually specific not only to a virus family but also to a species or distinct variations within a species. Though a vaccine can be effective at preventing virus infection, scientists must know what specific virus to make a vaccine for. This is a difficult challenge for viruses that are crossing into humans for the first time.
  8. Drugs and vaccines are under development. SARS-CoV effectively went extinct in 2004, shortly after it was contained, so there are no active vaccine research programs for that virus. Development of a MERS vaccine, however, is still underway. At UW–Madison, virologists are working on a vaccine for SARS-CoV-2, and in my lab, we are making progress toward therapeutics through close study of coronavirus proteins. The goal is to identify protein sites shared among different strains of coronaviruses, figure out how they work, and use those as targets to develop antiviral drugs.

Robert Kirchdoerfer is assistant professor in the Department of Biochemistry and the UW Institute for Molecular Virology.

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