In the race to develop a treatment for the rapidly spreading illness Covid-19, dozens of drugs are being tested around the world. It’s an urgent mission because the latest data suggests that some 20 percent of people infected have serious illness, and around 1 percent may die.
Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, told Congress on Wednesday that Covid-19 is 10 times more lethal than the seasonal flu.
The danger stems from the pathogen itself: a virus called SARS-CoV-2.
Teeny tiny viruses are one of the biggest threats that humanity has ever faced. They are behind some of the most devastating pandemics ever known. Even with all of modern medicine, we have only eradicated one virus, smallpox, which required a decades-long global mass vaccination effort.
SARS-CoV-2, the brand new foe, is spreading fast even as entire countries, like Italy, are locking down to prevent its transmission. Estimates of its potential impact vary, but Brian Monahan, the attending physician of the US Congress, told lawmakers Wednesday he expects between 70 million and 150 million people in the US to get infected with the virus over time.
Right now, doctors are using general treatment measures to control the symptoms of Covid-19, but there’s not yet a specific vaccine or cure.
Several factors make viruses like SARS-CoV-2 a particularly pernicious threat to humans. The good news is scientists have learned more about how they attack. They’ve also come up with ways to keep some of the deadliest of these tiny germs in check and are slowly inching toward cures. The question now is whether that research will bear fruit in time to blunt the blow of the Covid-19 pandemic and help us get ahead of the next outbreak.
Why viruses are such a tricky target for medicine
Viruses are the most bizarre germs. Using just a handful of molecules, they assemble into all kinds of tiny shapes, and with just a small set of instructions, they can wreak havoc across entire ecosystems and threaten crop harvests. They can travel between hosts through the air, water, soil, and droplets. They mutate rapidly. And they are truly everywhere, from the oceans to the skies.
Compared to infectious agents like bacteria and fungi, viruses are much smaller and simpler. In fact, viruses can even make other germs sick. Yet they’re so simple that most scientists don’t even consider them to be living organisms.
For instance, the poliovirus is just 30 nanometers wide. The SARS-CoV-2 virus behind Covid-19 is about 120 nanometers. Meanwhile, the E. coli bacterium is more than 16 times larger than SARS-CoV-2, and the human red blood cell is 64 times larger. A human cell uses 20,000 different types of proteins. HIV uses just 15. SARS-CoV-2 uses 33.
With all that extra space, larger pathogens like bacteria store the molecular tools they need to make copies of themselves and to fight off infections of their own. These tools are also what make bacteria vulnerable to antibiotics, drugs that interfere with molecular mechanisms in bacteria but not those of human cells, so they have a targeted effect.
But antibiotics don’t work on viruses. That’s because viruses don’t reproduce on their own. Rather, they invade cells and hijack their host’s machinery to make copies of themselves.
“Bacteria are very different from us, so there’s a lot of different targets for drugs. Viruses replicate in cells, so they use a lot of the same mechanisms that our cells do,” said Diane Griffin, a professor of microbiology and immunology at the Bloomberg School of Public Health at Johns Hopkins University. “So it’s been harder to find drugs that target the virus but don’t damage the cell as well.”
There’s also a huge variety of viruses, and they mutate quickly, so tailored treatments and vaccines against a virus can lose effectiveness over time.
Another factor that makes viruses so difficult to treat is how our bodies respond to them. Once the immune system detects a virus, it makes antibodies. These are proteins that attach to a virus or a virus-infected cell, marking it for destruction or preventing it from infecting new cells.
The problem is that a virus can cause a lot of damage and infect other people before the immune system readies its defenses. When those defenses kick in, they can cause other problems like fever and inflammation. And by the time these symptoms show up, the virus may already be in decline, or it may be too late to act.
“Often at the time that virus diseases present themselves, it’s fairly far into the replication of that virus in that person,” Griffin said. “Many symptoms of the virus disease are actually manifestations of the immune response to the disease, so often things are sort of starting to get better at the time that you actually even figure out somebody has a virus infection.”
How doctors and scientists currently fight viral infections
Researchers use two broad strategies to combat viral infections: slowing down the damage from the virus, and speeding up and strengthening the body’s countermeasures.
Antiviral drugs are one approach to slowing down viruses. Like antibiotics, these are drugs that hamper the virus without causing much collateral damage. “The majority of antivirals are targeting the viruses [themselves]. That means the components of the viruses, the viral enzymes, the surface proteins,” said Pei-Yong Shi, a biochemistry and molecular biology professor at the University of Texas Medical Branch. By attacking different parts of the virus, antiviral compounds can prevent a virus from entering cells or they can interfere with its reproduction.
For example, remdesivir, under development by Gilead Sciences, is being studied as a way to treat Covid-19. It works by blocking the SARS-CoV-2 virus from copying its genetic material, RNA, the instructions the virus uses to replicate itself. Remdesivir resembles a component of RNA, but when it’s taken up by the virus, it causes the copying process to stop. Crucially, remdesivir fools the virus, but not human cells.
Protease inhibitors are another class of antiviral drugs, like lopinavir and ritonavir used to treat HIV (the -vir suffix is used to denote an antiviral drug, similar to how -cillin denotes an antibiotic). These compounds block an enzyme in the virus that normally trims proteins down, allowing the virus to infect other cells. When the enzyme is blocked, the virus doesn’t mature properly, rendering it inert.
Researchers are also studying how to use antibodies to a given virus collected from engineered animals or from people previously infected with the same virus. By administering antibodies as a treatment, the recipient’s immune system can get a head start on identifying and eliminating the viral threat rather than waiting to build up its own antibodies.
There are also drugs like interferons that trigger a general immune response. These are a series of signaling molecules that make cells in the body more resistant to infection, inhibiting the spread of a virus while the rest of the immune system catches up. It’s mainly used to control persistent infections like hepatitis B.
But interferons can have severe side effects like inflammation, so it requires fine-tuning to treat a virus without doing more harm than good. Doctors have used interferon with other antiviral drugs to treat Covid-19 in China and researchers are investigating this approach as another potential therapy.
Doctors can also use a number of different therapies to limit the immune system’s response to viruses, like fever and inflammation, which can sometimes cause more damage to a patient than the virus itself. Anti-inflammatory drugs like corticosteroids and chloroquine are often used to lessen these symptoms.
And there are also vaccines for some viruses and efforts to develop new ones. These are treatments that coach the immune system to detect and fight off a virus before an infection takes place. These are powerful tools for controlling viruses across an entire population, but they’re tricky to optimize for a rapidly changing pathogen, and they require extensive, time-consuming testing to ensure they are safe for a wide segment of the population.
However, even if effective treatments enter the market, the virus will likely remain a threat. As we’ve learned with influenza (another respiratory disease caused by viruses), despite updated vaccines, new treatments, and a long history of public health responses, there are still between 12,000 and 60,000 flu deaths each year in the US. Covid-19 could remain a persistent threat, too.
The best way to fight a virus is to reduce the spread of infections
To be clear, the best way to fight a virus is to prevent infections in the first place. And that depends on public health measures during an outbreak, like quarantines and social distancing, as well as personal tactics like robust, 20-second hand-washing with soap.
While there is a large and growing body of research on drugs to control viruses, they are still few and far between. “We don’t have that many antiviral drugs for acute infections,” Griffin said. “You often don’t have any choice except to let it run its course.”
Developing new drugs can take years of testing, and by then, an outbreak may have faded, or another more threatening pathogen may have emerged. Even viruses for which we do have antiviral drugs, like influenza, the illness often isn’t detected in time to make it worth the treatment.
Other viruses like HIV can be controlled with drugs, but not eliminated, as hidden reservoirs of the virus remain in the body.
And within a population, there are always people who are more susceptible to infections, like people with depressed immune systems. For them, treatments and vaccines may not work, so they depend on the people around them to be immunized and to take proper infection control procedures.
All of which brings us back to prevention as the most effective way to combat viruses within a population. That means global coordinated action can be one of the best strategies to control the smallest pathogens. And simple tools like soap and water can be more effective at fighting a pandemic than the best drugs.