Coronavirus (COVID-19) How it works and what research needs to be done
Professor Tony Campbell
Coronaviruses are quite extraordinary, and to a biochemist absolutely fascinating. Their evolution is measured in thousands of years, instead of the typical millions, when using Darwin and Wallace time scales. However, all this may seem irrelevant in the present situation, when a coronavirus has had such devastating effects on individuals and families all over the world. Yet, in the medium to long term, understanding the evolution of these viruses may give us the necessary molecular information to combat them effectively. They cause disease in humans and animals, typically major respiratory and lung problems, and can lead to lethal organ failure. The current epidemic is cause by one labelled COVID-19. Dangerous coronaviruses previously were SARS and MERS.
Coronaviruses are composed of a single strand of positive RNA surrounded by a membrane, similar to that surrounding all our cells, in which are embedded proteins. Other single stranded RNA viruses include rhinoviruses, that cause the common cold, and influenza virus. On the other hand, HIV, that causes AIDS, has two single stranded RNA molecules inside its protein coat. Whereas the genome of many other viruses, such as Herpes, is DNA.
All viruses have to get into cells in order to replicate, so that they can make lots of copies of themselves. In the coronavirus case, the virus first attaches to a cell via the S-protein on its outside. S for spike, which is critical for the RNA to enter one of our cells. Once the RNA gets into the cell, it is immediately translated into proteins responsible for RNA replication. So large numbers of new RNA are produced, as well as translation into the four structural proteins that form the final virus particle. Key enzymes in this whole process are proteases that clip proteins into small ones, as well as the replication proteins. This includes RNA depended RNA polymerase, which is first made in a polyprotein. This means one long protein made of up of several proteins linked together, but inactive unless they can be separated. These proteins are released to be fully active by proteolytic cleavage, i.e. the polyprotein is clipped into bits. This is an amazing mechanism. But also, this is an obvious target for drugs to stop the virus replicating. There is much research that needs to be done, based on several key questions:
- How does the virus transmit between humans?
- Is it only by oral spray?
- Is it by touch on contaminated hands?
- Is it via touch on inert objects, such as door handles, taps, hand rails, and bannisters?
- Can it be transmitted via rain, fresh or sea water, as has been shown in the case of some other viruses?
- How many virus particles are needed to cause an infection in one person
- Critically, how much do we know about its stability outside the human body, in the air, water, and inert objects such as door handles?
- What is the best way to sterilise inert objects like door handles – soap, meths, chlorine disinfectant? The standard lab protocol is 70% ethanol.
If virologists have done this obvious research with other coronaviruses, where is it the published literature or via Google? It is vital the public know the answer to these seminal questions.
A critical question is where can we find published data on its stability in the environment? There are some easy experiments that should be done. For example, smear with active virus a door handle, a tap, clothes, and artificial skin, or add it to fresh or sea water. Leave it for various times, such as minutes to hours. Sample at each time point. Then, assay for active virus in a cell culture, and viable RNA using reverse transcriptase PCR. These are standard lab techniques. Has this been done? No media spokesperson on the TV, radio or newspaper has apparently ever talked about such necessary experiments. We also need a faster test than RT PCR, which can take several hours. There appears to be some data available on the internet about viral stability. SARS coronavirus is stable for 1-2 days, in faeces and urine at room temperature. But loses its infectivity after the use of normal disinfectants. Swimming pools contain chlorine so the virus should be destroyed by this. Much of the data on the Internet is all anecdotal, with no details of methodology or reproducibility provided. But, one important recent review published in the Journal of Hospital Infection 104 (2020) 246-251 by Kampf et al reviewed 22 published studies on the effect of various disinfectants on coronaviruses SARS, MERS and HCoV. They concluded that these viruses can survive for up to 9 days, which was reduced at high room temperatures. But they can be inactivated by the usual disinfectants, such as ethanal and hypochlorite. A rigorous study is now needed to measure the survival of COVID-19 on all surfaces. This data should be made available
The ‘powers that be’ and health care professionals are working flat out to cope with this crisis. The 111 phone line was initially rather confusing, but has been improved. We need test centres all over the country for easy patient access. We also need more labs that can set up the RTPCR test. This test is quite simple for anyone who is experienced in DNA technology, and would only need a lab with normal microbiological practice.
Clearly, avoiding coughing near other people, washing hands, and self-quarantine are obvious precautions to avoid infecting others, or indeed yourself. This article is a personal view, based on over 50 years as a professional biochemist. Watch this space for further information. Take care.
Anthony Campbell MA, PhD, FLS, FLSW
Honorary Professor, School of Pharmacy and Pharmaceutical Sciences, Cardiff University, and The Young Darwinian, 12/03/2020
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