As the end of World War II approached, the mass production of the newly developed antibiotic penicillin saved many soldiers by killing bacteria that infected their wounds. Since then, many other antibiotics have successfully treated a wide variety of bacterial infections.
However, while antibiotics work against bacteria, they are not effective against viruses. To eliminate these microorganisms, you need antivirals. Since the Covid-19 pandemic took hold, researchers and pharmaceutical companies have been working to find an antiviral that works to fight the SARS-CoV-2 coronavirus that causes the disease.
Why do we have so few antivirals available to us? The answer is to be found in biology: it lies in the fact that viruses use our own cells to multiply. It is therefore difficult to kill them without killing our own cells at the same time.
Antibiotics exploit human-bacteria differences
It is the differences between bacterial cells and human cells that make it possible to use antibiotics.
Bacteria are autonomous life forms, cells that can live independently, without needing a host organism. If they are, in some ways, similar to our cells, they also differ in many characteristics.
Unlike human cells, bacteria, for example, have a rigid cell wall made up of a compound called peptidoglycane. Human cells are devoid of it, and it is this difference that allows penicillin to be used against bacteria: this antibiotic indeed interferes with the construction of the bacterial cell wall.
The antibiotics which, like penicillin, prevent bacteria from making peptidoglycan can therefore inhibit the multiplication of bacteria without harming cells in humans who consume these drugs. We are talking about selective toxicity.
Viruses hijack our cells to replicate
Unlike bacteria, viruses cannot replicate independently: they need a host cell to do so. There is therefore a debate, which is still not decided, around the question of whether viruses belong to the living world.
In order to replicate, viruses enter a cell and hijack its machinery. Once inside, some viruses remain dormant, others replicate slowly and gradually escape from cells over a long period of time, and finally others quickly make so many copies of themselves that the host cell bursts. and die. The newly replicated viral particles then disperse, and infect new host cells.
Any antiviral treatment that occurs at some point in the virus’ “life” cycle may be effective. The problem is that if such a drug targets a replication process which is also important for the host cell, it is likely to be toxic to human cells as well. To put it simply: it is easy to kill viruses, but it is much more difficult to manage at the same time to keep the patient’s cells alive …
Effective antivirals target and disrupt a virus-specific process or structure, thereby preventing viral replication while minimizing harm to the patient. But the more the virus is dependent on the host cell, the fewer these specific targets. And unfortunately, most viruses have very few targets that can be differentially targeted.
Another difficulty is that the various existing viruses vary much more with respect to each other than the various species of bacteria between them. These all have genomes made up of double-stranded DNA and replicate independently by enlarging and then dividing in half, like human cells.
Viruses are extremely diverse: some have genomes made of DNA while others have genomes made of RNA; in some the genetic material is made up of nucleic acids (the other name for DNA and RNA) whose structure is single stranded, while in others these nucleic acids are double stranded. It is therefore virtually impossible to create a broad-spectrum antiviral drug that would be effective. against different types of viruses.
Some success stories of antivirals
There are, however, differences whose exploitation has led to some success. Influenza A is one example.
The virus responsible for this form of flu is able to trick human cells into getting inside. Once entered our cells, the virus must “undress”, that is to say remove its outer layer to release its RNA, which will then be transported to the nucleus of the cell, where viral replication will begin, in other words multiplication of the virus.
A viral protein called M2 protein (“matrix-2 protein” in English) is the key element in this process: it plays a facilitating role in the cascade of events which results in the release of viral RNA.
The researchers speculated that if a drug was able to block the M2 protein, the viral RNA would no longer be able to leave the viral particle to reach the nucleus of the cell. Logically, the infection would stop. This approach has proven to be successful:amantadine and rimantadine were the first antivirals targeting the matrix-2 protein to be successful against this virus.
The Zanamivir (Relenza) and theoseltamivir (Tamiflu), newer drugs have also been used to treat patients infected with influenza A or influenza B. They work by blocking a key viral enzyme, preventing the virus from being released from the cell and slowing the spread of the virus. infection in the body, which minimizes the damage caused by the infection.
Identify what makes SARS-CoV-2 specific
The development of a vaccine against the SARS-CoV-2 coronavirus could turn out to be complicated. It is therefore important to try in parallel to find antivirals that can effectively treat patients with Covid-19.
To achieve this, knowing the intricacies of the biology of SARS-CoV-2 is important, especially regarding its interactions with human cells. If researchers manage to identify elements specific to its survival and replication, they will be able to exploit them as weak points to develop an antiviral treatment that will have every chance of being effective.
This publication received the support of Judith Neilson Institute for Journalism and Ideas.