What is the COVID-19 / SARS-CoV-2 virus? Compared to most threats we encounter, the virus is small and simple. It doesn’t have sex, possess limbs or gills, or fill its lungs with air on a hill top and shout “It’s great to be alive!”. So is the virus alive, or just an organic robot? We talk of ‘killing’ the virus by washing our hands or using disinfectants, which means most of us think of it as a living creature of some sort. Whether we classify it as the ‘living’ or the ‘undead’, it is still a parasite that steals into our cells and helps itself to our enzymes and cell materials to make thousands of near-perfect copies of itself that go on to infect other cells in our bodies.
For the last few months I have been obsessively reading each major scientific discovery about the new SARS-CoV-2 virus, and delving into its close relatives that caused earlier epidemics of ‘severe acute respiratory syndrome’ (SARS). During the COVID-19 pandemic it has been difficult to stay asleep, and I wake wondering how the virus does this and that … then grab my iPad to search for the answer. Surprisingly, this research provides me with a lot of comfort. The more I get to know the inner workings of this terrible machine, the better I’m able to break it down to its basic parts. The more I research, the more clearly I can see the virus in my mind’s eye, and the more clearly I can see possible targets for treatment interventions and routes to vaccines.
Now that I know it better, I can follow it as it steals, like an experienced housebreaker, towards many different types of cells. When it finds an airway cell with a particular protein (the ACE-2 protein) jutting out of it, the prowling virus adjusts its twitching spikes into attack mode and latches on. As the virus pulls itself towards the cell, host cell enzymes innocently cut the attacking virus’ spike protein, allowing it to invade deeper into the host cell. The host cell is not aware that something is amiss at this stage, and doesn’t notice the invader virus quietly undressing so as to expose itself to the host’s enzymes and steal its raw materials.
Having found what it needs to get its engine cranking, the COVID-19 virus begins to make more copies of itself. This viral mess of newly-made proteins and nucleic acids is detected by the cell-sensing immune system. Now the host cell is shaken awake. Sensing the intruder and screaming for help, it releases messages in the form of cytokines to alert other cells that it is being attacked. The virus intercepts and destroys many of these. Some, however, get through to neighbouring cells, who react by going into lockdown, shutting their doors and halting their cell factories to prevent them from being hijacked by other prowling viruses. The messages also reach white blood cells who rush to the scene and release their own cytokines, mounting an inflammatory response against the virus. Unfortunately, sometimes the cytokine response can produce too much inflammation, causing the lungs and other major organs to shut down. As a last step, the viral progeny burst out of the host cell, but not before they steal its membranes, wearing them like a coat as they float away in the lung’s fluids to invade more of the host’s cells.
The COVID-19 papers I have been reading have been produced under considerable pressure. The authors of a paper that I read last night worked day and night for several months, existing on little sleep and working shifts in order to solve the all-important crystal structure of the virus spike that binds to the human ACE-2 receptor. This is crucial information that the world has been waiting for. These new papers are written with the utmost urgency by scientists working in exhausting conditions. They are fast-tracked by the editors, often appearing in quite a raw form, with typographical errors escaping the frazzled sub-editors. It’s a time of all-nighters, like in Bletchley Park, trying to break the Enigma code of the virus.
At the time of writing, around 80 SARS-CoV-2 vaccines are being tested. These will face a high attrition rate, and only a handful will pass the first hurdles of pre-clinical testing. The vaccines must protect the airways and organs targeted during infection, but without causing collateral damage to the fragile lung cells. Not all vaccines will be specific enough to stop the virus, and some could even worsen the infection. But the global efforts and co-operation of scientists and clinicians using modern vaccine technology put the odds well in our favour.
Professor Alex McLellan is an immunologist in the Department of Microbiology & Immunology at the University of Otago. He works on gene transfer and cell-based vaccines using viral (HIV-1) vectors.