Scientific Information about the COVID-19 (SARS-Cov-2) virus

There are many webpages repeating the essential information about how to protect yourself by hand washing and social distancing. Here we look a bit more into the science and draw some very practical conclusions as well. The format is Question and Answer.

Coronavirus by David Goodsell
Viruses are so small that even with unlimited magnification we would not be able to see them in ordinary light because the wavelength of light is too long. They are imaged using electron microscopy, but the best way to visualise them, or anything at this molecular scale, is with an interpretive illustration based on the electron microscope scan together with detailed knowledge of the shape of molecules and the electron clouds around them. This water colour painting by David Goodsell is hard to beat in that respect. Quoting his caption (see reference below) "It depicts a coronavirus just entering the lungs, surrounded by mucus [green strings] secreted by respiratory cells, secreted antibodies [the yellow three clubbed molecules] and several small immune system proteins [orange]. The virus is enclosed by a membrane that includes the S (spike) protein [big pink spiky clubs] which will mediate attachment and entry into cells..."

Illustration by David S. Goodsell, RCSB Protein Data Bank; doi: 10.2210/rcsb_pdb/goodsell-gallery-019

What is COVID-19

It is the disease caused by the virus officially named SARS-Cov-2, a member of the coronavirus family, which are all enveloped, positive strand RNA viruses. This means that the virus has an outer membrane envelope of phospholipids with trans-membrane (glyco)proteins and an inner 'naked' single stand RNA molecule formed in a way that acts directly as messenger RNA in a eukaryotic cell (obviously, then, a human cell). That is a horrifying thought as, once in the cell, it has direct access to the cellular machinery (like having the admin. password on a computer). This is because its RNA can be directly translated into protein by ribosomes in the host cell (positive because it 'reads' from 5' to 3' just like host cell mRNA).

Coronaviruses (so called because their trans-membrane envelope proteins (spike glycoproteins) make them look a bit like little crowns under an electron microscope) are common pests of mammals, including humans, for whom most of them just cause a cold. Most of these are of the genus alphaCoV or beta-CoV, SARS-Cov-2 is a beta-CoV. This little horror is among several recent zoonotic (transferred from other animals) coronavirus and appears to have originated from bats. It is closely related to SARS and MERS, most closely to the bat SARS strain BatCov RaTG13 (96% genetic identity), but recent work shows a pangolin might have been involved. Genome details can be seen in Wu et al. 2020. The spike proteins embedded in the envelope have on them a receptor binding domain (RBD) - this is the bit that attaches to a target on the mammalian cell. Its RBD fits like a key into the lock that is the ACE2 receptor on the surface of many epithelial cells throughout the body (especially the lining of arteries), but particularly vulnerable are those of the alvioli deep in the lung (actually all the way down the respiratory tract and throughout the alimentary canal, and it is emerging that intestinal problems can be added to the respiratory, with the possibility of damage to the liver bile ducts too - and the kidney's tubes). 

The virons (individual virus particles) are about 120 nm in diameter (so even very good masks won't keep them out - the point of masks is to block droplets of water and saliva in which virons may hitch a ride). The spike (S) glycoproteins attach to an ACE2 receptor on an epithelial cell. ACE2 (angiotensin converting enzyme 2) receptors are the chemical transducers for the ACE2 enzyme that is attached to the surface of these cells and functions to reduce blood pressure as part of a homeostatic system (which is why it is a target for high blood pressure management for those with cardiovascular diseases). It is a cruel irony that this essential transducer is hijacked by the coronavirus. One might think that blood pressure drugs that work by binding up ACE2 receptors (stopping them from reducing the amount of ACE2 around the cells) would limit the virus's access to them. However, whilst the action of ACE2 is protective of e.g. lung tissue, it turns out that the blocker drugs actually reduce the chance of pneumonia (probably because blood pressure is down regulated by increasing the leakiness of capillaries, including those around lung alvioli. It's as if the virus had already protected its king by castling that one.

What kills SARS-Cov-2 ?

On surfaces outside the body.
A recent study (Kampf et al 2020) examined the evidence for biocidal agents against human coronavirus in general, when used on inanimate surfaces (metal, plastic, etc.) and it is, at this stage, reasonable to assume the results apply to SARS-Cov-2. The headline news is that top of the list, 0.5% hydrogen peroxide and 0.1% sodium hyperchlorite killed it within 1 minute. For most people (without access to laboratory agents) that means household bleach works. Also 62-71% (or more) ethanol works, but not less than that concentration and frankly, it works much better at higher concentration. Most household cleaning and disinfectant products that do not contain bleach use benzalkonium chloride and some antiseptics use chlorhexidine, which are great on bacteria and some viruses, but not too good on this one (not totally useless, but you would not want to rely on them). Bleach has to be quite strong (0.1%) because 0.05% did not work very well. So, we recommend cleaning with strong bleach wherever it is acceptable to do so and if not, then an oxidising agent, especially in combination with a detergent. Look out for hydrogen peroxide (0.1%) for use on your hands as an antiseptic (it is really the only available oxidising agent of sufficient strength that is not unacceptably harmful to your skin). Detergents disrupt the lipid membrane of the virus and work to prevent it from sticking to your cells. Not proven, but we suspect that in combination with a phenolic such as hexachlorophene, chloroxylenol, chlorhexidine or triclosan, its action could be enhanced. Some medicated soap formulations include these with detergents.

Inside the body.
Intense research on drug therapies is progressing so fast that what is written here is likely to be already out of date. Still the front runner (mid to late March 2020) is the antiviral Favipirivar (Fujifilm Holdings and Zhejiang Hisun Pharmaceutical). This is a broad-spectrum antiviral which acts through inhibiting RNA-dependent RNA polymerase (RdRp) of RNA viruses. It has been used before - to treat avian flu in Japan and Ebola in Guinea. It is currently undergoing clinical trials (on patients). Also in clinical trials is the Gilead Sceiences Nucleotide prodrug Remdesivir. This one had shown great promise in vitro when combined with chloroquine phosphate (a malaria drug).   Other drugs are  being investigated for re-purposing (fastest possible track to the clinic) and in development, including some very novel nano-particle systems such as micelles that bind and capture virons using their spike proteins against them (rather like synthetic immune cells) - a good example is the NanoViricides system "like a venus fly trap for the virus" according to their press release. Of course the longer term solution is a vaccine and several are in development, but before that, we could expect direct antibody treatments. One of the front runners in that technology is CytoDyn with their monoclonal IgG4 called Leronlimab - it is a CCR5 antagonist. Regeneron Pharmaceuticals are also making monoclonal antibodies and nearing clinical trials. There are others.

Are viruses alive?

No, not according to our definition of life - the question above would be more accurately put as "what deactivates virons". They are obligatory parasites, but that in itself does not stop them being alive. The reason is that whilst other parasites depend on their host to provide a particular environment in which to flourish (for example providing essential nutrients), viruses require their host to provide parts of the autopoietically internal system. In other words, for a virus, the (M,R)-system is not complete, they do not have what it takes to be closed to efficient causation, their causal loops are not closed and they cannot function internally as a whole without their host. Even though they can reproduce, evolve and, within a host cell, perform some kinds of metabolism, they do not fit the I-F-B definition of life. The key difference between living and non-living parasites is that the former need their host only for external resources, whilst the latter require them to provide some missing internal parts (they are not causally whole).  - This question is now the subject of a short article published by United Academics at

How do we model the epidemic?

First, to get the latest high quality, responsible, quantitative reporting, I think it would be hard to do better than than the John Hopkins University dashboard (announced by Dong and Gardner, Feb. 2020), but it is entirely empirical (just gathering the figures and presenting them). Modelling is an attempt to go beyond that by representing the informative features of the dynamics, with a view to forecasting future outcomes. The foundation for most models for epidemic forecasting is the S-I-R differential equation system. The letters stand for Susceptible, Infected and Removed - see below. An elaboration of this approach lay behind the highly influential paper from Imperial College (London University) that is credited with changing public policy in the UK and to some extent in other countries, notably the USA. On the web, there are lots of demonstrations of simple S-I-R model systems and explanations of the thinking behind them. I just picked this one for the time being.

The S-I-R model represents the average dynamics of the infection in a large population and most of the practical models being used to advise policy makers are S-I-R with some of the generalities made more specific. Susceptible people are available to the virus to infect: the more of them there are, the bigger the outbreak. Infected people were susceptible and have now got the virus, the number of infected depends on the infection rate (related to, but not the same as how quickly the infection spreads) and also on the rate of removals. The overall dynamics is then a flow rate from S to I and from I to R. Let us recognise that R (removed) includes those who have recovered and those that have died and also those who have become inaccessible to the virus by isolation. The rate of increase of infected cases has to decline as R increases relative to S because the virus is then running out of people to infect. This is why it is such a good idea to stay at home and socially isolate - don't let the virus see you, be one of the R group and help lower the infection rate (as well as obviously  protecting  yourself).  Early in the outbreak, the UK Government was talking of maximising "herd immunity" to defeat the virus. They seem to have misinterpreted R as recovered (and therefore immune), forgetting that R includes also those killed by the infection. Thankfully the UK Government quickly changed their strategy and adopted a phased lockdown, with the effect of (mostly) hiding susceptible people from the virus. Much better!

The three most important elaborations of the model are: a) to represent spread in geographic space; b) to represent contact rates and therefore transmission probabilities among different categories of people and c) to disaggregate the population into specific groups (age and sex, certainly, perhaps also economic class or similar). We already know, for example, the differences in incidence of severe disease and mortality among age groups and sexes (males are quite a lot worse off, so are people who vape or smoke (though we did not find any significant stats on smoking yet) and it is thought that those with high blood pressure are at greater risk of severe disease (could be to do with the ACE2 access point) and blood group even has an effect (we will point you to the details on this as soon as we get the chance).

How does SARS-Cov-2 work ?

The RNA inside the virus acts directly as messenger RNA (mRNA) in the host cell (it is class IV in the Baltimore system, named after its author, Nobel Laureat (1975) David Baltimore who discovered the reverse transcriptase process and thereby retroviruses, contributing much basic science to defeat AIDS). Once inside the host cell, floating in the cytoplasm, the virus RNA strand inevitably encounters one of the host cell ribosomes. Despite it being alien to the cell and not capped in the correct way for reading, it seems the way it is folded (like a string of beads dropped onto the table) enables it to interact with the ribosome and con it into reading and translating the RNA sequence. Unlike our mRNA, it codes for every protein it requires in one go (it is monocistronic), so the protein product coming out of the feckless ribosome is a single giant polyprotein. On the face of it this cannot do anything because although it contains all the functional proteins, structural and enzymes, they are all joined together and unable to work like that. What is needed is an enzyme that can chop this polyprotein into the pieces in the right places, so the individual functional proteins are released: it needs a protease. The problem is that its own (virus encoded) protease that does this job is itself part of the polyprotein. The first job of this protease, in a mind boggling act of bootstrapping, is to cleave itself out of the polyprotein. Such self cleavage is relatively common in RNA (referring to self-splicing introns), but quite something when a protein molecule does it. Once the virus dependent protease has cut itself out, it chops the rest up. One of the resulting functional proteins is a virus encoded RNA polymerase, as the name suggests it is an enzyme that makes RNA (it is therefore an RNA-dependent RNA polymerase). This enables the virus to replicate within the hapless cell because this enzyme uses the cell's own stock of nucleic acids to synthesise negative stranded RNA, which can then be used a as template to make thousands of copies of the virus positive stranded RNA. This molecule is the target for the drug Favipirivar mentioned above.

What makes it a serious illness in a fraction of cases ?

On current figures (which could change a lot as mass antibody testing is introduced - see Lourenco et al (24-03-20), with response from Anna Seyburn in the British Medical Journal and Carson Chow’s response here),  it seems roughly 20% of those contracting COVID-19 suffer a serious illness. Of these, a fairly high proportion are starting mild and (often after about 5-7 days) go down hill very quickly. Clinical features indicate the reason is a derangement of the immune system and quite likely at least a big part of that is a runaway 'cytokine storm' of the homeostatic communications among immune cells. One of the key diagnostic features is the ratio of neutrophils to lymphocytes [NLR] (a healthy adult has 4-5 thousand neutrophils and between 1.5 and 3 thousand lymphocytes / mm blood: a ratio of around 2). On presentation at hospital, the ratio can be around up to  3 for someone who is going to get better*; above that and towards 10 (even in young patients), they are likely to need high-dependency care and much more than 12, they will be on the respirator, if it is over 20, they are very unlikely to survive (all rough figures, - listen to podcast from “This Week in Virology” for this insight: link below). The explanation is still a matter of active research, but the imbalance of immune cell types (more than these two, but they are key indicators) is strongly associated with serious derangement of the inter-immune cell signalling molecules cytokines, especially some of the interleukins (of which IL6 is receiving  particular attention). This, then, is clearly a case of the virus messing up communications and information processing in the immune system (see the section on homeostasis in our autopoiesis page for an introduction to cell signalling information in general). I hope to write more on this topic in the next few days (its 31st March today).

* The orignal scientific study predicts 50% severe illness if NLR > 3.13 and age > 50.

Tan et al (27th March) showed pathologically low lymphocyte counts predict severity and bad prognosis in the COVID-19 disease. They considered several plausible hypotheses for the loss of lymphocytes. Subsequently it is becoming apparent that at least one of these plays a critical role and is a target for drug therapies. Quoting them directly:

Inflammatory cytokines continued to be disordered, perhaps leading to lymphocyte apoptosis. Basic researches confirmed that tumour necrosis factor (TNF)α, interleukin (IL)-6, and other pro-inflammatory cytokines could induce lymphocyte deficiency.6” [note citation hyperlink takes you to Tan et al. where you can follow to the reference given below]

6.  Liao, Y. C. et al. IL-19 induces production of IL-6 and TNF-alpha and results in cell apoptosis through TNF-alpha. J. Immunol. 169, 4288–4297 (2002).

Interleukins (a class of cytokine), especially IL6 are now implicated in creating the severe form of COVID-19. See e.g. Cennimo (March 30th)  .


Kampf, G. Todt, D., Pfaender, S. Steinmann, E. (2020). Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents. Journal of Hospital Infection. 104. 246-251.

Wu, F. et al. (2020). A new coronavirus associated with human respiritary disease in China. Nature (on line).

Recommended short video  It is on youtube and although I was sceptical at first, I watched it and think it is brilliant.

Quick Links and Resoures

This is fast moving science, so, especially for professionals and those with more advanced interest, here are some resources on the web.

The World Health Organisation (naturally).

Wikipedia (of course)

CDC COVID-19 page   Very useful especially for clinicians interested in the USA approach.

Medscape news collection (a great place to get the latest from clinic and lab)

Genetic Engineering & Biotech News Updates on progress of development of treatments (all kinds everywhere).

Nature Biotech. article on fast-tracking antiviral therapies

Updated in this bulletin:

RND systems - developing diagnostic tests, assays and treatments. Especially this bulletin

This Week in Virology   With News (like a podcast) from the clinical coal-face