Q&A – All your antiviral questions and answers

In this article we will answer some of the questions we get asked about our work. If you have a question you’d like answered, please email us. The most recent updates are  added to the bottom of the article, and numbered in sequence.

Q1. What is an antiviral exactly?
As the name suggests, an antiviral is a type of drug or medicine that acts against (‘anti-‘) a virus (or viruses). Most antiviral drugs are designed to work against one specific virus, and they mostly do this in one of two ways: by blocking (or inhibiting) cell receptors so viruses can’t bind to and enter healthy cells, or, by slowing down the virus’s ability to replicate. This reduces the viral load in the body and allows the immune system to get on top of the infection.

Q2. Why are antivirals important?
At last count, there were 219 viruses known to cause diseases in humans, and more are being discovered every year. This is actually only a tiny fraction of all the viruses that are thought to exist – a figure that has been estimated to be 10³¹ (a 10 with 31 zeros – a simply enormous number!)

Some of the more common viral diseases are Influenza (the flu), HIV, Meningitis, Covid-19, Pneumonia, Human papillomavirus (HPV), Herpes, SARS, Hepatitis and Rotavirus. You might also be familiar with Dengue, Zika, Yellow fever, Ebola, Marburg, MPox and others. Over the last few years, we have all witnessed the effects of a global pandemic caused by the virus SARS-CoV-2 (aka Covid-19). Effective antivirals are critically important for both the treatment of current viral diseases and to be prepared for future pandemics.

Q3. What is a virus?
A virus is a tiny, infectious parasite that replicates only inside the living cells of a host, such as a human, plant, animal or bacteria. They are made up of a small piece of genetic code (DNA or RNA) that is enclosed in a protective coating of protein, and sometimes an additional lipid (fat) envelope. A complete virus particle is called a ‘virion’.

Viruses are very small – so small in fact that they are described as ‘submicroscopic’ – meaning they can’t even be seen with an ordinary light microscope. They are found in almost every ecosystem on Earth and are the most abundant type of biological entity. Outside of a host cell, viruses are inert, and are not considered to be ‘living’ things.

Viruses have receptors that allow them to attach to a cell, and from there they enter the cell and release their genetic material. This viral material takes over the cell and forces it to become a virus factory, rapidly producing thousands of new copies of the original virus. With most viruses, the cell eventually dies and bursts open, releasing the newly made viruses, which then spread throughout the host (and potentially to new hosts), where the cycle can repeat. This is what happens during a viral infection.

The viruses that infect humans are currently grouped into 21 families (more on this later). Those families are defined based on the shape and structure of the viruses, their chemical composition, and how they replicate. Both individual cells and whole organisms have defences against viruses, and viruses have in turn evolved their own unique counter-defences. All of these factors are significant in relation to the design of antivirals as different approaches are required depending on the properties of the virus being targeted.

Q4. Viral mutation and antiviral drug resistance
Viruses include genes that contain the encoded biological information of the virus, in the form of either DNA or RNA. As the virus is replicating, it can create some imperfect copies of the original. This is known as a ‘mutation’, and while most mutations fail, even if only a few survive, the process of natural selection can quickly cause them to become dominant. A beneficial mutation can cause the emergence of a new strain or type of virus, such as we have seen with Covid variants. Any viral strain that is more transmissible, better at evading our immune system, and more resistant to treatments and vaccines, becomes much more of a threat to human or animal health.

Because regulatory authorities are concerned about drug resistance, it is an important part of the testing and approval phase for any new drug. Antimicrobial resistance in bacteria, that has given rise to ‘superbugs’ is currently a serious global health concern. There is also growing alarm about a surge in resistance to two antiviral drugs that are important to the treatment of HIV, as reported in Nature.

Recently in New Zealand, it was reported by Stuff that health authorities here are concerned that use of the Covid-19 antiviral drug Molnupiravir has caused viral mutations that may have led to an outbreak, leading to calls that it should be prescribed sparingly, if at all.

Because of the ways antiviral drugs work, many are susceptible to viral mutations and can become less effective as a result. In the case of Molnupiravir, the drug is designed to directly interfere with the process of viral replication at the RNA level, and is supposed to cause enough significant mutations that the virus is no longer able to function. However, with every mutation comes another chance for the virus to gain the upper hand.

Other antivirals are designed to bind to a particular part of a specific virus, blocking cell receptors and preventing the virus from binding to and entering a potential host cell. Any mutation in the structure of the proteins that form part of the virus’s external enclosure can quickly render this antiviral ineffective.

As if these problems weren’t enough to deal with, sometimes a virus just stops responding to a previously effective antiviral for no known reason. This is called ‘spontaneous resistance’.

The problem of viral mutation and drug resistance is just one of the disadvantages facing the current regimen of antivirals and one of the many hurdles facing the pharmaceutical industry as a whole. Kimer Med’s antiviral compound VTose works differently from the antivirals described here, which is one of the reasons we think we can overcome these problems, and develop an effective broad-spectrum antiviral drug.

Q5. What does ‘broad-spectrum’ mean?
In this context, ‘broad-spectrum’ refers to a medication or treatment that is effective against a wide range of organisms – in this case, viruses.

As we’ve already mentioned, most antivirals have been designed in a very ‘pathogen-specific’ way – meaning they are most likely to only work against a specific virus. However, in some cases, certain antivirals have been found to have some effectiveness against another virus too. There is a tendency to refer to any antiviral that works against more than one virus as ‘broad-spectrum’, but this is not an accurate description, as that is still only a very narrow segment of the full spectrum of available targets.

Q6. How do antiviral drugs work?
Earlier, we mentioned that most antivirals are designed to work against a specific virus, and in a specific way. Antiviral medicines are designed work differently depending on the drug and the type of virus. Antivirals can:

• Block receptors on the cell surface so viruses can’t bind to and enter healthy cells
• Boost some aspect of the immune system, helping it fight off a viral infection
• Lower the viral load (the amount of active virus) in the body.

Kimer Med is developing an antiviral that is unique as far as how it works, so we need to add a fourth bullet point to that list:

• Bind to viral dsRNA and trigger apoptosis (programmed cell death), preventing the virus from replicating and eliminating it from the body.

Q7. How you you test your compound against viruses
Our initial testing is done in a laboratory setting, and is sometimes called ‘in vitro’ – which literally means ‘in glass’.

The test we usually use is called a CPE (Cytopathic Effect) reduction assay. Here’s how it works…

When a virus infects a cell and undergoes lytic replication, the cell is eventually damaged or killed. This is known as the cytopathic effect, or CPE. The CPE reduction assay is a common testing method used to assess the effects of drug candidates against viruses in a laboratory setting. 

First, scientists grow a layer of cells in the wells of a special plate. Next, they introduce the virus they want to study into the plate, allowing it to infect the cells, by adding a specific amount of the virus to the cell culture. The amount of virus introduced is such that after a few days, in the absence of treatment, 85% to 100% of the cells will die from CPE. 

At certain, measured dosages, they also introduce the antiviral compound to the infected cells. This allows comparison of cells with and without treatment. At the end of the test, the number of surviving cells is measured, using a special dye.

A 100% positive result means that at a certain dose of the antiviral compound, there was a 100% reduction in viral CPE, indicating that the antiviral compound is rescuing the cells, i.e. preventing the virus from damaging or killing the cells.