In the battle against viral infection, we discussed in a previous article the issues surrounding our over reliance on Antibiotics to target and treat most cases of viral and bacterial infection. In addition to Antibiotics and the lesser explored Phage Therapy, we have another card up our sleeve to play - the Antivitral.
AntiViral therapy and medication has been used and reserched and explored since the early 60’s and already has allowed us to be able to treat diseases, such as HIV, Herpes, Hepatits etc in ways that we are able to control them and their spread without necessarily destroying them completely.
Antivirals first came on the market in the early 1960’s with Idoxuridine being introduced by William Prusoff for the herpes simplex virus in 1963. Since then almost 90 antiviral drugs have been approved for the treatment of 9 various diseases. HIV, Hep B, C, Herpes, Influenza, Cytomegalovirus (CMV), Varicella Zoster virus (VZV) which causes chicken pox and shingles, Respiratory Syncytial Virus (RSV) a respiratory virus and Papillomavirus infections (HPV) that causes anogential warts are all diseases that have been effectively handled and treated by antiviral medication. The effectiveness of these drugs has been able to largely control these infections and their transmission in the population.
How Anti-Virals work
Unlike Anitbiotics, Anti Virals do not destroy their target pathogen but inhibit it’s development. Viruses create an infection with in a host by replicating their cells. They connect onto receptors on a healthy cell and transmit their DNA that infects a healthy cell, and creates more fo the viral cells. Antivirals block this receptor process and thus inhibit the development of the virus into an infection. The issue with this method of controlling infection is that antivrials need to be targetted to particular cells within a host to prevent an infection. This is a time consuming and labour intensive process and with the adaption of most viruses and bacterias adapting regularly and readily, targetting specific proteins can become a latent attempt of chasing your tail, as by the time you have developed a targeted antiviral, the virus has mutated or adapted to become something else.
The other question is that anti-virals ned to target infection cells without having any detrimental effect on host cells. Herein lies the issue, with proliferated antiviral use, are we damaging a hosts normal immune function? The answer is yes and this issue was highlighted by the early approaches to HIV with AZT and Ribavirin. These early drugs whilst making headway in preventing a viral infection from proliferating within a host, also, over long term use, had damaging effects on the host immune function which downgraded their ability to fight other viruses or infections. (W Heagy 1, C Crumpacker, P A Lopez, R W Finberg)
But the key may be in our application of antivirals and how we can use and manipulate them to be more effective in our fight against viruses. More recent advances in antiviral research are looking to make Antivirals more targeted to specific proteins or even parts of proteins within a pathogen cell that are unique to the infection but do not resemble any of the human host cells. This targeted approach is far more effective and is hoping to identify particular elements that are common across many of the viruses adaptions and variations which makes it much more effective as an inhibitory agent and applicable across a broader spectrum of the virus in all its mutations and forms.
So why aren’t we using more antivirals? In the wake of the Antibiotic Apocalypse, Antivirals are having a resurgence. There is research being conducted in Switzerland which is currently trying to develop targeted antivirals in response to the COVID virus. Viruses in contrast to bacteria are not independent organisms with their own cell walls that can be attacked and destroyed. Viruses differ fundamentally from bacteria as they aren’t their own organisms. As Kathie Seley-Radtke, medicinal chemist at the University of Maryland, Baltimore County explains “viral pathogens live inside our own cells and depend on our proteins for most of their needs, so they offer no such easy targets.” There are few natural living Antivirals and so any antivirals that we do create, need to be made from scratch, and be targeted to specific proteins. The difficulty is not to hurt the host cells or host DNA whilst attacking the virus DNA.
Anitvirals also need to be administered in the initial stages of infection to be effective. If the infection has proliferated and is already taken hold in the system, antivirals won’t be as effective in treatment. There is some evidence to suggest that in the treatment of COVID patients, an Antiviral (AT457) developed by Roche and Atea Pharmaceuticals has had an effect on assisting in the recovery of sufferers. It unfortunately does not help heal patients from the infection but it has shown encouraging signs of helping with recovery and is being considered as a rollout to assist with mild sufferers to help ease the burden on front line services.
In this way Antivirals may help to bring about effective control of a virus or superbug and may assist with being a precursor to treatment and those suffering with generic or mild symptoms. However, the administration of this medication needs to occur at the early stages. Virologist Mark Heise of the University of North Carolina at Chapel Hill says that “The faster you can take the drug, the more you can limit the virus’s ability to spread,” Whilst it doesn’t eliminate the virus it does help stop the spread from person to person. This is the limit of the antiviral… it isn’t a cure, and this is where the body’s immune system must come up with the ultimate solution to eliminate the virus. And in those who are already immunosuppressant then this can be the straw that breaks the camels back as it were.
The question is ultimately, can we develop antiviral therapy that will not ultimately damage our own immune function and host cells? Also, in taking antiviral medication long term is there a risk of damaging other organs in our body. Let’s take PrEP, the well known HIV pre-emptive medication that helps to prevent the transmission of HIV. The usual administration of PrEP is one tablet daily. Scientific studies have shown that in some cases (although rare) some side effects of this medication can create creatinine and transaminases - both enzymes that can effect liver and kidney function. Stanford Health Care actually lists Tenofovir (a widely used PrEP medication) being linked to increased risk of Kidney damage.
So it could be that in the processing of these antivirals we can create strain on organs and have undesired long term effects, which perhaps we are not quite aware of yet as we haven’t had long enough exposure to the medication and studies to investigate it’s efficacy. This is an area of concern when new drugs are rolled out liberally and we continue to rely on them to waylay concerns over viral infections. It’s worth watching and waiting to see what the research will say about long term Antiviral medication. But for now, it is a worthy an interesting area of investigation as we do strive to find new ways to battle our greatest foes of bacterial and viral infections. Watch this space.
