Dead Man Walking…

Firstly a massive apology to all our friends, family and fans! It’s been awhile since we’ve graced your screens with one of our off the cuff and yet hilariously outrageous blogs. It’s safe to say we’ve been a tiny bit distracted with getting another little project up and running. Now that’s in full swing we can get back to putting the fingers to the keyboards and taping out some much needed time wasters for you ladies and gentlemen, in a time when we are finding ourselves with a lot of spare time. Safe to say living amidst a global pandemic, it’s piqued our interest and we’ve decided to take an investigative look at the wonderful yet dangerous world of virology. What is that you ask? Read on dear friends and discover for yourselves…

Well depending on which website you go to it’ll tell you that Virology is either the study of viruses or a branch of science that studies viruses, same same but different?. Either way we are currently looking at viruses whilst we have a show about pandemics playing in the background. Why a show about pandemics? Well that should be pretty self explanatory given we are currently all locked at home because of one. Many of us for the first times in our lives are having to adapt to what could potentially be the new normal for the next six or so months. With COVID-19 still ravaging many parts of the world, the fight to flatten the curve and keep people at home is an ongoing battle. Even with some locations reporting low to no new cases people shouldn’t feel they are being given the green light to become complacent and go back to their old way of life. Should we even be going back to business as usual or should we be using this as an opportunity to check in and make some changes that will better all of humanity and the environment? We’ve all heard about the wildlife now returning to clean waters, such significant reductions in air pollution that it’s visible from space and the release of animals back into their natural habitats.

It was around 1898 that scientists first started to isolate viruses and assign them to specific diseases. Over time as technology has improved and with that so has our ability to classify and identify viruses. It wasn’t until 1960 that Nobel Prize winner in Medicine and Physiology, Peter Medawar (for his integral work in the area of transplantation), to paraphrase, defined viruses as a piece of nucleic acid surrounded by some extremely bad news. Early pioneers in virology had a limited collection of medicines, techniques and equipment available to them to be able to classify and identify viruses as microbial agents. At the time of their discovery, microscopes lacked the sufficient power to see viral agents. How to grow cell cultures was unknown to scientists and probes such as antibodies and nucleic acids to mark infectious agents were not yet known and identifiable. Thankfully technology has come a long way and we are better able to research and study viruses, and from there develop medications such as antivirals and vaccinations.

A virus is actually quite different to bacteria or fungi, the other two types of infections we as humans have to face. Whilst bacteria and fungi are cells that can survive on their own accord, viruses are much smaller than a cell and require host cells to provide the energy and nutrients required to survive and replicate. Most of the time hosts are unwilling or ignorant to the fact their body and cells have been invaded. Virus’s spread and transfer through direct cell to cell contact such as through respiratory passages, open wounds and the sharing of bodily fluids. Or they hitchhike a ride through an intermediate host such as mosquitoes and the saliva they inject when they bite. Studies have shown that viruses can replicate both inside insects and the host cells ensuring smooth transition from one host to another. A good example of this is the viruses that cause yellow fever and dengue fever. Viruses attach themselves to hosts cells through receptors on the cell’s surface much like interlocking puzzle pieces. They then begin the process of invading the cell and replicating either within the cell until it bursts and spreads integrating itself in to a cells DNA so that each time the cell replicates it also replicates the virus

So now that we have a basic understanding of viruses, let’s delve a little deeper into them and look a little closer at the main one affecting the world today because let’s be real this isn’t the first pandemic the world has suffered and it won’t be the last. Throughout man’s time on earth viruses have ravaged the population, think the Spanish flu or in more recent memory Swine flu. Over time we have developed the science and medicine necessary to combat viruses through vaccines and various other means. But there will always be viruses out there that we do not know about it. It is estimated that at any one time there are over a million undiscovered corona viruses within the animal population, however most of these strains of the virus aren’t transferable to humans. Bats appear to be the prevalent carriers and studies as recently as 2015 in the Yunnan province of China showed the genome sequence of the Betacoronavirus (RaTG13) in the Intermediate Horseshoe Bat was 96% identical to that of SARS-CoV-2. Fast forward to February 7th 2020 and it was learned that a virus even closer to SARS-CoV-2 had been discovered in Pangolin. It’s similarities registered a 99% genome sequence.

Now before you go blaming the poor little pangolins as being the cause of COVID-19 recent studies of the Malaysian pangolin have shown they are less similar with only a 90% genomic concordance. Not sure what this means? Well these results have led scientists to the conclusion that the virus isolated in pangolins is not responsible for the COVID-19 pandemic currently raging. Furthermore if we have previously been able to identify the SARS-CoV-2 virus in animals why is it now causing such a problem for humans. Well further studies have shown that whilst the virus identified in bats can’t enter human cells and the one isolated in pangolins can, the comparison of these genomes suggests that the SAR-CoV-2 virus is the result of a recombination between two different viruses, the process where virus’ restructure themselves in order to overcome adversity and adapt to new environments and hosts, In other words it’s a chimera between two pre-existing viruses. This recombination mechanism has previously been seen in coronaviruses in particular in explaining the origin of SARS.

For recombination to occur, the two divergent viruses must have infected the same organism simultaneously. That still leaves questions unanswered, the main one being in which organism did the recombination occur. Was it a bat, was it a pangolin or was it another species? And above all under what conditions did this recombination take place? Whilst the threat of man made biological weapons produced in labs is a valid risk to the world’s population in this case it looks like mother nature is taking care of things herself.The environment and mother nature has a way of creating its own biological time bombs or chimeras that are just as deadly to the world as man made viruses. The world has known of these threats for centuries in one form or another, some called them curses, some call them diseases and overtime they became known as viruses. It’s even kept up to date with technological advances and we can give them to our computers.

To further confuse people it is because of the process of recombination, that the specific strain SARS-CoV-2came into existence and formed into a virus that is transferable to the human population. It shares genetic similarities with other human respiratory coronaviruses such as SARS and MERS. However the subtle differences in the virus’s genetic makeup translates to significant differences in how readily it is transmitted and the symptoms of infection experienced.. SARS-CoV-2 has all the same core genetic makeup as the original SARS-CoV which caused global panic and outbreak in 2003, and it shares genetic similarities with MERS which emerged in the middle east in 2012.This new virus has weaponised it’s itself, it has versions of the same general equipment for invading cells and replication, however SARS-CoV-2 has a totally different set of genes called accessories, which give this new virus its advantages in specific situations. Not enough is known yet about the roles these accessories play and all of the advantages they give SARS-CoV-2 however an example can be seen in the MERS virus in which a particular protein shuts down a cell’s ability to sound the alarm about viral invaders.

The scientific community has banded together throughout the pandemic in a surprisingly fast and effective manner to pull together results and research allowing us to understand SARS-CoV-2 and it’s disease COVID-19. We understand how it infects the human body, how it’s transferred, partly how it came about and potentially a vaccine to combat this coronavirus in the future. The current pipeline for SARS-CoV-2 vaccines isn’t as full as we would hope but that comes down to the tough science and time it takes to actually make a successful vaccine for human use. The trials alone would take years to seek approval from the various governing bodies before being released world wide. The reason behind this is that no current vaccines for coronaviruses are on the market and no large scale manufacturing capacity for these vaccines exist, we need to build these processes and capacities.

Creating these processes and capacities for the first time can be tedious and time consuming. Funding has been awarded to several highly innovative players in the field, many of them may be successful in eventually creating a SARS-CoV-2 vaccine. After consulting many medical journals and spending a weird amount of time on Google looking at YouTube videos and reading about how vaccines are created we’ve come to understand, after further Googling and videos, in attempting to make vaccines most of the companies that are trialing them are targeting something called RNA. What is RNA? Well read on and get lost with us…

Ribonucleic acid (RNA) is a bit like Deoxynucleic acid (DNA) in the fact that both are nucleic acids composed of a sugar, a phosphate group and a nitrogenous base. We all learn about DNA being the building blocks of all life forms, but don’t often hear about RNA’s. Like DNA, RNA is assembled as a chain of nucleotides, but unlike DNA, RNA is found in nature as a single strand folded onto itself, rather than a paired double strand. There are 3 types of RNA’s that work together to produce proteins that are essential in various biological roles in coding, decoding, regulation and expression of genes.Messenger RNA (mRNA) transcribes the genetic information from the DNA, Ribosomal RNA (rRNA) directs the translation of mRNA and Transfer RNA (tRNA) is involved in the actual transfer of the initial genetic information into protein synthesis. Are you with us so far? You’re probably wondering what all of this has to do with the process of developing a vaccine… well many viruses encode their genetic information using an RNA genome.

New technology has allowed us to take a step away from traditional vaccines and to start to take a look at using RNA in vaccines however it has not yet been used on a global scale — meaning scientists can’t yet predict what manufacturing problems might crop up. The idea for this type of vaccine is that a group of RNA’s would attack the SARS-CoV-2 virus when it tries to infect the body. Our bodies naturally have these RNAs however with age and comorbidities they diminish. The vaccine would be designed to boost the specific RNA required for combatting COVID-19. Other groups, such as Duke, the Imperial College of London and Fudan University in China, are also exploring this promising approach. RNA technology leaves researchers with many unsolved challenges, compared to more traditional vaccine types that are already mass produced. One Of these problems is storage to ensure the vaccine doesn’t degrade, which is especially tricky because by nature RNA‘s are intrinsically unstable molecules.

Yet another problem the world is facing in developing a vaccine is securing enough accessory chemicals, critical for vaccine production. Many of the RNA based vaccines are formulated with “magical chemicals” for lack of better words, that look like oil droplets. These accessory materials are expensive and hard to make in large quantities. With all the technology available no one has figured out how to scale up their manufacturing or get the costs low enough so that everyone can get the vaccine.

More traditional methods for vaccine creation are also being researched, where variants of the SARS-CoV-2strain are placed into the vaccine with the idea that our body’s own immune system will be able to develop the antibodies required to fight off the virus when it tries to invade the body. . Pharmaceutical companies GlaxoSmithKline, Novavax and Clover are all at various stages of testing this approach. Protein subunit and recombinant protein vaccines use an approach that is similar to existing vaccines used for HPV and Hepatitis B.

This is all sounding quite promising however even this more traditional approach to vaccines comes with its own distinct scale-up challenges. These vaccines may require booster shots to provide lasting protection against COVID-19. For other vaccine candidate types, scientists are unsure if one dose is enough to generate and maximize a protective immune response, meaning each person might have to be given multiple doses which further complicates an already complicated manufacturing scale-up. All the issues of development, manufacturing, scale-up and distribution, would be nearly insurmountable for one group to tackle on their own. Of the confirmed active vaccine candidates, 56 are being developed by private industry developers, while 22 projects are being led by academic, public sector and other non-profit organizations, according to all the googling we did whilst researching vaccines.

The pandemic has brought unprecedented collaboration among vaccine developers across the world. The National Institute of Health is launching a public-private partnership to speed up COVID-19 vaccine and treatment options, known as ACTIV — short for Accelerating COVID-19 Therapeutic Interventions and Vaccines. Scientists continue to work tirelessly to curb the pandemic through developing a safe, effective vaccine that can reach people across the world. The so-called lab coat wearing experts hope that the enthusiasm for collaboration on a COVID-19 vaccine will transfer to other vaccination efforts in the future.

So to sum it all up into even more words, we are a little while off a vaccine curing us all from the disease COVID-19 caused by SARS-CoV-2. There are going to be newer and even deadlier viruses for us to contend with in the future and now is the time, if not earlier for the world to be identifying them, creating vaccines, medicine and or nanomites to ensure that we do not have to go through pandemic after pandemic. If there is one good thing to come out of all of this though and that’s the environment is starting to spring back. The holes in the ozone layer are starting to close over, animals are migrating back to their regular patterns and we are seeing species that haven’t been seen in years. So when you sit at home and try to find a silver lining to all that is happening in the world around you it’s this. Life is bouncing back, the planet is bouncing back and so will mankind.

The only hope is that we bounce back with some form of respect for what we have and learn lessons from all of this. What’s the saying, “Lack of preparation leads to piss poor performances”. In taking a look back we can safely say the world was not prepared for a virus on this scale or how to contain it. A vaccine is still most likely 12 months away if not longer and each country needs to ensure that it is able to manage in times of crisis that includes Pandemics. Well that’s enough from us and it feels good to finally get something down for you all. Also if you are interested in hearing the voices behind the blog head over to your favourite podcasting app and download “Conversations with The Captain and Commander” trust us you’ll enjoy it. For now it’s adios amigos, stay safe and stay home to save lives…

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