Perhaps one of the greatest failings of modern medicine is the lack of effective treatments for viral infections, especially for colds.
The depth of the failure is rather impressive.
We all have suffered grievously with colds, noses can really ache, throats can be searingly sore, lungs heave with the agonies of racking coughs, and what does medicine have to offer?
Take a decongestant and usually your nose remains just as runny and bothersome. Take a cough syrup and chances are excellent your cough will not diminish or decrease.
The need is enormous, and the options keep coming up short.
So when I read this week in The New England Journal of Medicine that a new drug has been tested to treat influenza virus infections, I was eager to find out, had the viral wall been dramatically breached?
The name of the drug is baloxivir marboxil, or just baloxivir. A good language hint when it comes to the names of drug, is that any chemical claiming to kill viruses or stop their infections, ends with the letters ivir. The more familiar Tamiflu’s official generic name is oseltamivir, and this new drug is baloxivir.
So what is the story with baloxivir, does it cure influenza viral infections?
The Challenge of Finding a “Viral Antibiotic”
Many people ask us, if amoxicillin cures ear infections and pneumonia, and it’s been around for 70 years, why hasn’t science come up with an antibiotic for viruses?
The answer lies in the nature of viruses. They are more different from bacteria than bacteria are from us. Both bacteria and people eat food to survive, and many bacteria take in oxygen, like us, to burn our fuel to perform life functions. Viruses don’t do any of these things. Viruses do not eat, they do not breathe, they create no or little waste.
If bacteria are single-celled versions of us, eating, breathing, secreting waste, reproducing, then viruses are an alien life form all together. Viruses are really just a string of DNA or RNA that serves one function- to act a code to force an infected cell to make more viruses. Surrounding the little strip of viral genes inside every virus is a coating of various proteins that trick the host cell into letting it in and guide its genes to the cell’s genetic apparatus.
The point is that viruses, to a very large degree, are more bits of replicating information, much more so than a form of life as we know and experience life. Another aspect of the reality of viruses is that they are not alive without living cells around. No living cells, no viral growth and replication, the virus simply sits there waiting for the right cell to come along.
This is why finding a viral antibiotic has been so very, very hard to accomplish. Regular antibiotics are chemicals that stop a living cell from performing a vital function. This whole idea works great for bacteria whose chemistry is different enough from ours that we can find chemicals that say stop them from forming cell walls. Our human cells have no cell walls, so such blockers don’t hurt us. That is exactly how amoxicillin works. Take amoxicillin, and susceptible bacteria stop being able to make cell walls, they die, they stop eating us, and the disease is cured. As noted, we don’t have cell walls so they don’t hurt our cells. Very nice.
One last challenge to mention is fascinating. There appears to be a difference in the damage done to our tissues from bacteria and viruses. Bacteria actually eat our tissue, just as we eat plant and animal material. They clump around a spot and munch away. If you kill them before they spread, there is sometimes not that much damage left over to heal. For example, with a bacterial ear infection, the pain comes from a growing ball of pus behind the eardrum, shrink that ball a bit and all the tension leaves the eardrum, and the pain suddenly ceases. Like leaving a tiny bit of air out of a tight balloon, it doesn’t take much air to be let out to leave the balloon very limp.
But viruses destroy whole linings of what they infect. Get a cold and the whole lining of your nose, then throat, then lung can be destroyed. It is like the lining gets burned. Not a deep burn, but still a burn. In this setting, kill the virus, and you still have a burn to heal. Imagine if you burned your hand with a mild burn, you would first remove the heat, say get your hand out of the scalding water. But even if you end the heat, in some ways “cure” the cause of the burn, you still have a burned hand. You won’t feel good until that burn heals, maybe 5 or more days later.
So, even if we invented a chemical to stop viruses from replicating, even if we got rid of one all together, it could be that if you give it after the lining of the nose, throat, and lungs are burned, you will still feel lousy.
Taking a viral antibiotic might change lab levels of virus in your nose, but your nose may still feel awful.
Two Past Attempts to Kill the Influenza Virus
In the past 2 types of drugs have been developed to kill the influenza virus.
The first keeps the influenza virus from reproducing. Remember, all that viruses can do is get into the cell (invade) and then force the cell to make a zillion copies of itself to repeat the cycle again (replicate).
The first set of anti-influenza drugs stopped the virus from replicating. But as of now, the influenza virus has mutated to not be bothered by these drugs, so we don’t use them or hear of them much anymore.
The second keeps the influenza virus from invading our cells. That’s the famous Tamiflu. There are two big problems with Tamiflu. It has been shown to have no or little impact if you take after 48 after the very first symptoms have occurred. This is a big problem since it usually takes a few days to be sure you have an illness and that it is miserable enough to need help. Even worse, the drug not only has little help to offer 48 hours after the first sneeze, it helps less as time goes on, from the first sneeze. The second problem is that in chidlren, Tamiflu is strangely associated with very disturbing mood and behavioral disturbances, including successful suicidal planning and action, particularly amongst adolescents and youth.
Given that one group of anti-influenza virus drugs increasingly no longer work against the influenza virus, and another group doesn’t work after 48 hours, and then in some young people can cause dangerous alterations in thinking and behaving, it was again welcome news that a new drug is on the horizon.
So, how does baloxivir do?
Let’s start with how it works. The influenza virus has a nifty way of taking a small snippet of our cell’s RNA and uses it to help copy its own DNA. Block that, and no viral replication. Baloxivir does just that.
The article looked at two groups.
One was 389 people ages 20-64 years old. They compared baloxivir to placebo and found that if you took the drug you saw symptoms improve for at least a day (21.5 hours to be exact) in about 50 hours. If you took placebo you got to that level of feeling better after 78 hours.
Curiously the use of baloxivir led to the emergence of some mutated forms of the influenza virus, some of which were no longer killed by the baloxivir.
The other was a group of 1366 patients, including 20-64 year olds, and 12-19 year olds. In the adults, use of baloxivir got to symptom relief in about 54 hours, and placebo in 80 hours, very similar result.
In the adolescents the difference was 36 hours, even more than in adults. A comparison with Tamiflu found the time to relief of symptoms was 54 hours.
For this group, time made a huge difference. Starting the baloxivir before one had 24 hours of symptoms created a 33 hour improvement in how fast you got better, but if you waited more than 24 hours after symptoms started, you might only see a 13 hour benefit in using the baloxivir.
In terms of resolving all fever, placebo took 42 hours for that to happen and baloxivir 24 hours. Return to normal health took an average of 129 hours for baloxivir and 169 hours for placebo to achieve.
- Viral infections are a totally different event than bacterial infections. They cause widespread, if very shallow, damage to the lining of the tissues they infect. So killing a virus may still leave you with a burned lining.
- Influenza viruses burn the lining of the nose, throat, and lungs.
- This makes use of a drug that kills an influenza virus not as helpful as a drug that kills bacteria in bacterial infections.
- The many year experience with Tamiflu (aka oseltamivir) is consistent with these observations. Use of Tamiflu often fails to cause dramatic recovery. The longer one waits to start it, the less impact it has, and that impact drops off dramatically if you have been ill for 48 or more hours, not that long.
- Now comes baloxivir, and it has eerily the same sort of impact on the course of the illness one gets from the influenza virus. Notice how little impact it has even 24 hours after the first sniffle, not very long at all.
- For Tamiflu, and now the new drug, baloxivir, relief is in small increments. Even the largest impact on the illness saves the person taking the drug no more than 1-2 days of illness.
- The fact that these drugs have little impact after even 1-2 days of illness, and only can reduce the time you are ill by 1-2 days, is in great contrast to the story with the antibiotics that kill bacteria, in which case one can see huge relief even after many days of being ill. I think this is because viral infections cause a burn like level of damage that needs to heal even if a drug kills off the virus.
- Tamiflu, over time, has been found to cause infrequent, but quite serious side effects that raise questions about the overall benefit of reducing the symptoms of the illness by only 1-2 days, at best.
Putting this all together, the quest for the medication that you can take at any time during a course of an infection with influenza virus is not over. We have no such drugs for the common cold at all, and the drugs for influenza virus infections are quite limited. For very, very severe and dangerous influenza virus infections, even a slight benefit can result in a major difference in outcome, but not so for influenza infections that do not require hospitalization.
We do hope one day the very large challenge of finding a reliable, very safe, and highly effective treatment for all our viruses can be met.
In the meantime, at least we have immunizations for the influenza virus, a good way to reduce their impact safely.
To your health,
Dr. Arthur Lavin