A newfound furrow on the surface of some viruses may be key to their ability to trigger disease. That could make this furrow a prime target for drugs to treat colds and other illnesses.
Sarah Butcher and Johan Neyts led a team of scientists in a search for new antiviral drugs. Both are virologists (Vy-RAHL-uh-jizts), scientists who study viruses. At the University of Helsinki in Finland, Butcher focuses on the structure of viruses. Neyts works at the University of Leuven in Belgium. He is searching ways to treat viral infections.
The scientists tested how well various compounds fight viruses in cells being grown in the lab. One chemical in particular caught their attention. It prevented one kind of virus — an enterovirus — from making copies of itself. This prevented the virus from spreading from cell to cell.
The researchers next used a technique called cryo-electron microscopy, or cryo-EM. It flash freezes molecules in a very cold liquid. That allows a very fine-scale view of the molecules’ structures.
Using cryo-EM, the scientists took a close-up look at how the virus and potential drug interacted. It showed that the compound seems to jam a previously unknown pit, or pocket, in the virus’s shell.
The researchers described the pocket June 11 in PLOS Biology.
This may work in other viruses, too
The germ they had been working with belongs to a virus family called picornaviruses. So the team decided to look at other members of that family. Some are rhinoviruses, which cause the common cold. Some are other enteroviruses, ones that can cause more dangerous infections, including hand, foot and mouth disease. Many of the related viruses, they now report, seem to have a similar pocket.
No drugs yet exist to treat rhinoviruses or enteroviruses. But the new finding offers hope for making such drugs, says Susan Hafenstein. She studies viral structures at the Pennsylvania State University College of Medicine in Hershey. She did not work on the new study. But she calls the pocket “an excellent target” for making drugs that might work against many such viruses.
One challenge is that these viruses mutate — change — easily and often. That ability makes it “easier for them to escape a drug,” she says. The best bet? Target some process that the virus needs to use to survive, she says. That way, if a virus mutates to avoid the drug, it could die as a result.
A virus infects cells by injecting its genetic material inside them. That genetic material then takes over the host cell’s machinery and makes more viruses. In picornaviruses, a shell surrounds the virus’s inner core of genetic material. That shell, previous research suggests, changes shape as these viruses prepare to inject their genetic material into a new host cell.
That shell is also where Butcher and Neyts’ team found the new pocket. Their compound of interest nestles into the pocket and sticks. Once there, it seems to lock itself in place. That stops the shell from changing its shape and releasing its genetic material. “This locking prevents the virus from infecting cells,” explains Butcher.
The researchers tested several similar compounds, too. Some were able to block many picornaviruses. That suggests that the pocket is a key feature in this virus family, Butcher says. That means it likely that it plays an important role in the virus’s life cycle.
The team is now working to make those compounds even more effective against the viruses, Neyts says. That’s an early step toward turning them into drugs to treat disease.
antiviral A virus-killing substance prescribed as a medicine.
biology The study of living things. The scientists who study them are known as biologists.
cell The smallest structural and functional unit of an organism. Typically too small to see with the unaided eye, it consists of a watery fluid surrounded by a membrane or wall. Depending on their size, animals are made of anywhere from thousands to trillions of cells. Most organisms, such as yeasts, molds, bacteria and some algae, are composed of only one cell.
chemical A substance formed from two or more atoms that unite (bond) in a fixed proportion and structure. For example, water is a chemical made when two hydrogen atoms bond to one oxygen atom. Its chemical formula is H2O. Chemical also can be an adjective to describe properties of materials that are the result of various reactions between different compounds.
compound (often used as a synonym for chemical) A compound is a substance formed when two or more chemical elements unite (bond) in fixed proportions. For example, water is a compound made of two hydrogen atoms bonded to one oxygen atom. Its chemical symbol is H2O.
core Something — usually round-shaped — in the center of an object.
enterovirus A common family of viruses that can cause mild, cold-like symptoms or more severe illnesses.
genetic Having to do with chromosomes, DNA and the genes contained within DNA. The field of science dealing with these biological instructions is known as genetics. People who work in this field are geneticists.
germ Any one-celled microorganism, such as a bacterium or fungal species, or a virus particle. Some germs cause disease. Others can promote the health of more complex organisms, including birds and mammals. The health effects of most germs, however, remain unknown.
host (in biology and medicine) The organism (or environment) in which some other thing resides. Humans may be a temporary host for food-poisoning germs or other infective agents.
infect To spread a disease from one organism to another. This usually involves introducing some sort of disease-causing germ to an individual.
infection A disease that can spread from one organism to another. It’s usually caused by some type of germ.
jam (verb) To block a sound or interfere with the ability to interpret that sound. Or something that works like a jamming agent to interfere with the function of some system.
life cycle The succession of stages that occur as an organism grows, develops, reproduces — and then eventually ages and dies.
molecule An electrically neutral group of atoms that represents the smallest possible amount of a chemical compound. Molecules can be made of single types of atoms or of different types. For example, the oxygen in the air is made of two oxygen atoms (O2), but water is made of two hydrogen atoms and one oxygen atom (H2O).
shell The protective, hard outer covering of something.
virologist A researcher who studies viruses and the diseases they cause.
virus Tiny infectious particles consisting of RNA or DNA surrounded by protein. Viruses can reproduce only by injecting their genetic material into the cells of living creatures. Although scientists frequently refer to viruses as live or dead, in fact no virus is truly alive. It doesn’t eat like animals do, or make its own food the way plants do. It must hijack the cellular machinery of a living cell in order to survive.