Why viral infections are so hard to treat
By Amy Rogers, MD, PhD
Hopes for a miracle cure for COVID-19 spread almost as fast as SARS-CoV-2. But it’s extremely unlikely that a “cure” will be found. Almost a hundred years after the discovery of penicillin, we still have few drugs that are effective against viruses. Viruses exist in a gray zone between living and nonliving things, a status that protects them from our best pharmacologic interventions. Here’s why.
Viruses are a minimalist form of life. Imagine if Marie Kondo took a living cell and decluttered it of everything that was not absolutely essential — and then threw away a few more things that can be borrowed instead of owning. You would get a virus.
Single-celled life, such as bacteria, can do all kinds of things. They can eat, travel, defend themselves, communicate with other cells, produce waste, pass on information to their children, and they can make copies of themselves (reproduce). Viruses, on the other hand, are much smaller than cells. They are not cells. A virus is a tiny package of information (either RNA or DNA) wrapped inside a protective shell (a protein coat). A virus cannot eat, cannot move under its own power, does not produce waste, and is unable to reproduce on its own. Thinking like a science fiction writer, I imagine a virus as a small golden chest buried in the desert by an advanced, alien civilization. Inside the chest are blueprints for a doomsday device. Human explorers encounter the chest, open it, build the device, and blow themselves up. In the final scene of this little tale, another small golden chest drifts through space in search of a new planet to infect.
In a similar way, a virus is impotent until it encounters a living cell. When they come together, the virus inserts its information (RNA or DNA) into the cell and forces the cell to build a doomsday device (more viruses). The virus hijacks the machinery of the cell in order to reproduce itself according to the instructions coded in its own RNA or DNA. Eventually the cell either bursts or dies of exhaustion, releasing many new viruses to infect more cells.
This peculiar way of life is the reason why we have very few chemical treatments (drugs) against viral infections. The first really good drug to treat infectious diseases was penicillin. Penicillin works against some classes of bacteria. But neither penicillin nor any newer antibiotic can kill a virus or treat a viral infection. Why?
It’s pretty simple. The cells of bacteria are fundamentally different from human cells in a couple of ways. Those differences provide targets for chemical poisons that harm the bacteria, but don’t affect the cells of the human patient taking the drug. To illustrate, imagine if a poison could kill cells that contain chlorophyll (the photosynthesis chemical that makes plants green). A human could take this poison and be just fine. Same with antibiotics. They are poisons for bacteria but not for people because the bacteria possess some target molecule that we don’t.
In contrast, viruses present very few potential targets to distinguish them from humans. Seems counterintuitive, right? Viruses are more different from us than bacteria are, yet they have fewer unique features that we can target with drugs.
The answer to this riddle is in the life cycle I just described. Viruses have been thoroughly decluttered. Instead of having their own unique enzymes and systems and structures for metabolism and reproduction (like bacteria do), viruses use ours. We cannot design a drug to inhibit food consumption by viruses because our cells digest food for them. We cannot design a drug to block the assembly of viral proteins because our cells are doing the assembly for them.
Antiviral weapons are rare and difficult to invent because viruses use human shields.
For these reasons, the end of the COVID-19 pandemic is unlikely to come from a cure. There are a small number of good antiviral drugs in use today. Mostly they are used to manage or treat — not to cure — viral infections such as HIV, hepatitis B, herpesviruses, and influenza. One happy exception is hepatitis C , which can be cured by antiviral therapy. But these drugs are not as powerful or broadly useful as most antibiotics are.
We may stumble upon some already-existing pharmaceuticals that help the immune system fight off the coronavirus. Clinical trials are in progress testing favilavir, remdesivir, and chloroquine for effectiveness against SARS-CoV-2. Such drugs might increase patient survival, but they would not fundamentally change the course of the pandemic.
The coronavirus pandemic will end with herd immunity, not with a cure. We will acquire that immunity either the hard way or if all goes well, through vaccination.