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update 69: NAC, glutathione, oxidative stress, thrombosis

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glutathione – far more than just an antioxidant

So we start with a closer look at glutathione, and its backbone amino acid chain, including the amino acid cysteine. Cysteine has the formula HO2CCH(NH2)CH2SH. The thiol sub-chain (SH) is important because it can bind to another form of the molecule, with S binding to S (oxidised form) rather than binding to H (reduced form) as here. So, as Dr Seheult explains, if you have two glutathiones, in this reduced form (2GSH), oxidised via hydrogen peroxide (H2O2), you will create a bond (GS-SG) between the two oxidised glutathiones, together with water. This happens in the oxidisation processes in our cells.

Seheult next mentions ADAMTS13, which is also known as von Willibrand factor-cleaving protease, so it’s a zinc-containing enzyme. VWF polymerises via disulphide bonds, and ADAMTS13 can help in disrupting that process, I think. Seheult diverts us by mentioning the disulphide bonds that connect the spiral strands of keratin in hair. A ‘perm’ reduces the molecular structure, breaking the disulphide bonds, so that the individual strands can be straightened, or made more curly, after which ‘you neutralise the perm agent’?? via H2O2, allowing disulphide bonds to re-form keeping the new hair structure in place. That was almost interesting.

So what can we do to assist these glutathione-based processes in relieving oxidative stress? This is apparently where N-Acetylcysteine (NAC) comes in. This molecule, which is ‘the N-acetyl derivative of the natural amino acid L-cysteine’, is ‘an antioxidant and disulphide breaking agent’, according to a 2018 review article in the Journal of Free Radical Research (not a political journal). So NAC is a reducing agent, which, like cysteine, has an SH bond. It breaks disulphide bonds and adds hydrogen, reducing viscosity. NAC has been used as a mucolytic inhalant, and as an agent against tylenol (paracetamol) overdose. How this last effect works is complex and I’ll try to comprehend it.

As Seheult explains it, NAC would act on the metabolite of paracetamol in situations of overdose. In such cases the liver metabolises paracetamol via an alternative pathway, by means of the toxic metabolite NAPQI, which depletes the liver’s glutathione. NAC replenishes the glutathione, but I won’t try to analyse the mechanism here. The main point is that NAC’s glutathione-boosting effects may have potential in dealing with Covid-19 symptoms. According to the above-mentioned review article, glutathione depletion is related to oxidative stress associated with a wide range of illnesses and pathologies, as well as in general ageing. So, a 1997 study in Italy looked at H1N1 flu and NAC treatment in a randomised, double-blind trial of 262 individuals of both sexes, most of them suffering from non-respiratory chronic degenerative diseases. They were divided into a placebo group and a NAC tablet group for a period of six months. No difference was found in both groups contracting the virus, but the majority of the placebo group (79%) came down with symptomatic forms, compared to only 25% of the treatment group, a significant difference. The study concluded that NAC treatment ‘appears to provide a significant attenuation of influenza and influenza-like episodes, especially in elderly high-risk individuals.’

So, recognising that this update is 2-3 months old now, I went online to see if NAC treatment is being used, or more comprehensive trials are being undertaken, as I note that, though case-rates are still disturbingly high, especially in the USA, death-rates are somewhat reduced.

An article from NCBI (the National Center for Biotechnology Information), which post-dates update 69 by a couple of weeks, presents only a hypothesis:

that NAC could act as a potential therapeutic agent in the treatment of COVID-19 through a variety of potential mechanisms, including increasing glutathione, improving T cell response, and modulating inflammation.

However, it didn’t seem as if any effective clinical trials focusing specifically on Covid-19 had been completed at the time of the article. A much more recent article (July 14) in Future Medicine (not such a promising name, given the urgency), presents more biochemical detail of NAC’s action, along with the anticoagulant heparin, and mentions ongoing clinical trials, but not specific results. It also mentions NAC treatment as a preventive for frontline ICU workers and general healthcare workers. It may be that such treatment is already being applied.

So, returning to update 69, Seheult cites another article from 2010 in Biochemical Pharmacology which showed that NAC inhibited viral replication (here the virus was H5N1) and reduced inflammatory cytokines, and again they suggested it as a potential treatment in the case of future influenza pandemics. Another small trial suggested some limited efficacy for NAC in the treatment of acute respiratory distress syndrome (ARDS).

So on it goes. A 2018 article found that ‘[NAC] improves oxidative stress and inflammatory response in patients with community acquired pneumonia [CAP]’. This oxidative stress reduction may be more important for Covid-19 cases because of the possibility of thrombosis due to the effect on VWF. A 2013 study found a significant decrease in a number of coagulation factors with NAC treatment. Of course, with this blood-thinning facility, NAC should not be used for patients with increased bleeding risk during or resulting from surgery. In any case I note that NAC is on the WHO list of most safe drugs or treatments.

And there are more studies. Another 2018 study found that NAC could reverse cerebral injury from strokes exacerbated by diabetes. The study concludes that ‘the diabetic blood and brain become more susceptible to platelet activation and thrombosis’, and that NAC appears to offer protection against the risk of stroke. The study’s explanation of the process here gives me an opportunity for further revision:

[NAC protects against stroke] by altering both systemic and vascular prothrombotic responses via enhancing platelet GSH, and GSH-dependent MG elimination, as well as correcting levels of antioxidants such as SOD1 and GPx-1.

So that’s platelet glutathione, and glutathione-dependent methylglyoxal, and the antioxidants mentioned are superoxide dismutase 1 and glutathione peroxidase 1. The ScienceDirect website does an amazing job of informing us about every known aspect of molecular biochemistry, just saying. Its material on glutathione and its catalysis is exhaustive and exhausting. And it looks as though the silver lining to the tragedy of Covid-19 may be a spike in further research into this and other essential elements of the molecular basis of immune systems.

Dr Seheult goes on to cite one more study, which found that ‘NAC administration promotes lysis of arterial thrombi that are resistant to conventional approaches…’, principally by acting on VWF, and that it is even more effective in combination with ‘a nonpeptidic GpIIa/IIIb (glycoprotein) inhibitor’, with no observed worsening of symptoms or outcome vis-a-vis normal haemostasis.

So I’ll end this piece wondering how things are going with NAC and other applications to reduce both respiratory and thrombotic symptoms in regions where the virus continues to be spread through a mixture of government, business and personal irresponsibility and stupidity. The battle to keep people alive and relatively healthy will, I think, ultimately win over the stupidity of some, but at a terrible and tragic cost. Vaccines are in the offing, but fear, indifference and ignorance will probably have the most adverse influence on their effectiveness.

References

Coronavirus Pandemic Update 69: “NAC” Supplementation and COVID-19 (N-Acetylcysteine)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261085/

https://www.futuremedicine.com/doi/10.2217/fmb-2020-0074

https://www.sciencedirect.com/science/article/pii/S0304416512002735

https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/methylglyoxal

Written by stewart henderson

August 2, 2020 at 12:46 pm

Covid-19 – conspiracies, remdesivir

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tricky micky plumpeo, vying with old frumpy to become US muckraker-in-chief

Canto: So, getting back to Covid-19, I want to look at two unrelated issues – the limited approval of remdesivir as a treatment, and the claim by the US government that the virus escaped from a lab in Wuhan. What do you think?

Jacinta: Well let me briefly address the second matter – I haven’t yet looked into the claim, but I will say that, IMHO, the current US federal government is possibly the largest misinformation machine on the globe at present, and I won’t be happy till I see every member of that non-administration in jail.

Canto: Okay, be prepared for a life of misery. I agree though, that Pompeo is a slimeball, and it’s very likely that this is largely designed as another blame-shifting distraction by the US maladministration. I don’t remember hearing about this from any news source before Pompeo announced it.

Jacinta: Well it’s interesting that, in investigating this, we have to contend with, and generally ignore, two of the most untrustworthy governmental sources of information on Earth, the USA and China. So thank dog for independent journalists, scientists and investigators. We need them so much at this time. The Washington Post has a 2000-word article on the issue, posted on May 1, undoubtedly in response to moves by Frumpy & co to get the US public to blame China for the pandemic. The article describes an assessment from the US intelligence community:

While asserting that the pathogen was not man-made or genetically altered, the statement pointedly declined to rule out the possibility that the virus had escaped from the complex of laboratories in Wuhan that has been at the forefront of global research into bat-borne viruses linked to multiple epidemics over the past decade.

Canto: ‘Pointedly declining to rule out’ means very little. They’re making a point of saying it’s possible? Isn’t it more likely to have come from the ‘wet markets’ – wet with blood that is – as a result of that traditional Chinese fondness for dining and medicating on exotica?

Jacinta: ‘Murky’ is how the WaPo describes the origins. Some scientists are saying it’s highly likely to have been ‘naturally transmitted’, others, not so sure. But the thing is, the scientists are the ones to trust on this, certainly not the Chinese or US governments. And even then you need to check those scientists’ allegiances.

Canto: I should also point out, as so many scientists are doing, that now is not the time for playing the blame game. Knowledge is power, and we need to be pooling our global resources, and our knowledge, to combat this and future pandemics. We need to try and build trust, not to sow distrust. And this isn’t to say that accidents can’t and don’t happen in virology and microbiology labs around the world, including in the USA.

Jacinta: The WaPo also has much to say about renowned virologist Shi Zhengli, team leader at the Wuhan Institute of Virology, which is being targeted by the Trump administration’s propaganda campaign. According to Shi, ‘the institute never possessed the SARS-CoV-2 virus’, while Wuhan’s health commission has found, or claimed, that the first person who died of the virus purchased goods at the Huanan Seafood Wholesale Market.

Canto: So it may have come from seafood?

Jacinta: Don’t know. Probably they sold more than seafood there, or it was part of a wider market. Anyway, many virologists, including US scientists who’ve worked with her, vouch for Shi’s extreme rigour and brilliance. But clearly that won’t stop the US government’s attempt at character assassination. I’ve heard they’re trying to say, or infer, that the virus was engineered at the Wuhan lab – and no doubt millions of Yanks will believe this brilliant theory, that the virus was engineered by mad scientists and then let loose to kill thousands of their own people before being unleashed upon the world – to be followed up by Chinese chem-trails, no doubt.

Canto: And not just Yanks. Anyway let’s move on to a happier topic. Remdesivir.

Jacinta: Well the news is that the FDA in the USA has issued an Emergency Use Authorisation for remdesivir, and the Gilead company which owns this pharmaceutical, has issued a company statement (on May 5), and here’s a quote:

Gilead’s overarching goal is to make remdesivir both accessible and affordable to governments and patients around the world, where authorized by regulatory authorities…. Gilead is in discussions with some of the world’s leading chemical and pharmaceutical manufacturing companies about their ability, under voluntary licenses, to produce remdesivir for Europe, Asia and the developing world through at least 2022. 

I’ve listened to an interview with Gilead’s CEO Daniel O’Day, and he was making all the right caring-and-sharing noises…

Canto: Can we revisit what remdesivir is and does?

Jacinta: Of course. For starters it’s not a cure, it’s essentially ‘an investigational antiviral drug’ (I’m quoting again from the company statement) which, O’Day is careful to point out, ‘has not been approved by the FDA for any use’ (meaning presumably besides this emergency use). He also admits that the drug is the subject of multiple ongoing clinical trials and ‘the safety and efficacy of remdesivir for the treatment of COVID-19 are not yet established’. It’s a nucleoside analogue, one of many that have been formulated over the years, and dozens have been approved for use in treating viruses, cancers, bacterial and other pathogens. Nucleoside (and nucleotide) analogues are designed to resemble naturally occurring molecules used to build the RNA and DNA so essential to our biology. Some of the best-known nucleosides are cytidine, thymidine, uridine, guanosine, adenosine and inosine. The difference between a nucleoside and a nucleotide is that nucleosides are nucleobases linked to a sugar molecule while nucleotides are linked to phosphate groups (oxygen and phosphorus).

Canto: And the key is that in creating an analogue which functions differently from the real thing, they’re trying to obstruct the replication of the pathogen that takes up this analogue, right?

Jacinta: Yes, you’re getting it. Remdesivir actually has several modifications to the nucleoside structure while still functioning as an analogue – that’s to say it still manages to trick the virus into utilising it, and so becoming dysfunctional in terms of replication. A professor of chemistry and biochemistry, Katherine Seley-Radtke, describes the process in relatively simple terms:

Remdesivir works when the enzyme replicating the genetic material for a new generation of viruses accidentally grabs this nucleoside analogue rather than the natural molecule and incorporates it into the growing RNA strand. Doing this essentially blocks the rest of the RNA from being replicated; this in turn prevents the virus from multiplying.

She writes that remdesivir is a three-times-modified version of the adenosine molecule. Firstly, it’s a ‘prodrug’, in that it has to be modified in the body before it becomes active. The active form has three phosphate groups and is then recognised by the RNA polymerase enzyme of the virus. The second modification is a carbon-nitrogen group attached to the sugar, which is the key to terminating the RNA strand’s production. The third modification is a little change to the molecule’s chemical bond, replacing one nitrogen with a carbon, which prevents one of the enzymes of the virus from recognising and excising ‘foreign’ nucleosides. Remdesivir’s modified adenoside remains in the RNA chain, ultimately terminating further production. Got all that?

Canto: I refuse to confirm or deny. But I can read too. There’s a proper clinical trial of the drug being conducted in the USA at present, and other trials elsewhere. Preliminary results show faster recovery in a statistically significant number of patients, but it isn’t a cure, and will likely be part of a cocktail of treatments as other and hopefully even better antivirals are formulated. This follows the approach to treating other dangerous viruses such as hepatitis C and HIV. It’s about getting the death rate, and the badly-affected rate, down. This is as important as a vaccine, at present.

Jacinta: And I’ve heard it’s quite a tricky drug to manufacture, so getting supplies up and sharing expertise globally will be key factors in saving lives.

References

https://www.washingtonpost.com/national-security/chinese-lab-conducted-extensive-research-on-deadly-bat-viruses-but-there-is-no-evidence-of-accidental-release/2020/04/30/3e5d12a0-8b0d-11ea-9dfd-990f9dcc71fc_story.html

https://www.gilead.com/news-and-press/company-statements/gilead-sciences-statement-on-remdesivir-global-supply

https://theconversation.com/remdesivir-explained-what-makes-this-drug-work-against-viruses-137751

Written by stewart henderson

May 7, 2020 at 4:17 pm

Covid 19: How the SARS-CoV-2 virion does its thing

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filched from The Economist, a US website

Canto: We’ve been lapping up the excellent Medcram series of videos on the pandemic, and we’re now at episode 32 I think, from March 6, and a week’s a long time in Covid-19-world.

Jacinta: Yes and back then the largest number of confirmed cases outside of China was in South Korea, and that, I now understand, was largely because of the massive testing they’d engaged in – so elsewhere the infection was being under-reported, or barely known about.

Canto: And today, April 23, South Korea has dropped down to 27th on the list of reported cases. Interesting to note that by March 6 South Korea had tested some 140,000 people, almost 100 times more than the USA had done. As we know, the CDC had stuffed up by producing a flawed testing kit, which resulted in crucial delays.

Jacinta: And weren’t the South Korean tests more effective? They used a different type of test didn’t they?

Canto: According to a Bloomberg article referred to in the video, South Korea’s tests had a 95% sensitivity rate, much higher than those of the USA at the time. But neither the article nor the video went into detail about the type of test.

Jacinta: So I think the standard type of test used is called PCR, or RT-PCR, which means reverse transcriptase polymerase chain reaction, but I don’t really know what that means or how the tests work.

Canto: We’ll look at how the tests work later. Let’s use this video 32 to help us understand how this virus gets into a host cell and replicates.

Jacinta: Ok, so we have a cell with its nucleus, and its DNA in there, and outside the nucleus is the cell’s cytoplasm containing organelles such as ribosomes, mitochondria, lysosomes, microtubules and the like. The DNA is transcribed into single-stranded precursor messenger RNA. The RNA is then transported into the cytoplasm, where it’s modified, giving it a ‘five prime cap and a poly-A tail’. So one end has its nucleotide altered by the enzyme guanyl transferase. It has to be a guanine nucleotide connected to the mRNA with a particular triphosphate linkage. The poly-A tail is a string of adenine bases. These modifications form what’s called post-transcriptional RNA processing. Then the ribosome, about which we’ve learned so much from Venki Ramakrishnan, reads the mRNA from the five-prime end to the three-prime end. That’s in the ‘positive’ direction. It reads the nucleotides three at a time and comes up with a code (here it gets a bit vague), so that when three particular nucleotides line up, ‘a specific amino acid has to be placed on there’. And transfer RNA is involved here. So a by-product of this process is a protein (consisting of amino acids), made by the ribosome. That’s translation, not so clearly explained. Anyway, proteins are the central building blocks of our bodies, without which not.

Canto: Okay, sufficient unto the day. And remember, this transcription/translation process is known as ‘the central dogma of molecular biology’, in case you’re tested. Now we’ll turn to the virion. So the cell membrane that the virus needs to penetrate is a lipid bilayer. That bilayer is hydrophilic on the outside (that’s facing out from the cell and into the cell) and lipophilic on the inside. The coronovirus has the same lipid bilayer, with embedded proteins, notably the s-proteins or spike proteins which we know are used to attach to host cells. There are other structural proteins such as m-proteins (membrane proteins) and e-proteins (envelope proteins). Inside is the large RNA genome, protected by n-proteins (nucleocapsid proteins). Presumably there are other proteins too. Now, note that this is one virion, which is the built structure housing the virus (what enables it to survive for however long outside of a host), but also including the virus itself, which is essentially the genome. For the virus to replicate and spread, all those structural proteins have to be reproduced too.

Jacinta: The s-protein just happens to fit, like a key in a lock, a receptor protein in the human host cell membrane called the ACE-2 receptor. These ACE-2 receptors, full name angiotensin-converting enzymes, are found in our lungs, and elsewhere, such as the heart, the kidneys and the intestines. Once this connection is made, the viral RNA is released into the cytosol. And as it happens, this viral RNA also has a 5 prime cap and a poly-A tail just like the host’s mRNA. It isn’t clear from the video whether this is because it gets modified within the cytoplasm or it’s already ‘primed’ so to speak. Anyway, the cell’s ribosomes start to act on this rogue RNA as it would on its own mRNA. Meanwhile the structural proteins from the viral membrane are incorporated into the host membrane, possibly earmarking it for destruction.

Canto: The ribosome makes a protein from the viral RNA, called RNA-dependent RNA polymerase (RdRP), or an RNA replicase. The protein somehow makes another complementary strand of RNA, running in the opposite direction, from which the ribosome makes more protein, which makes more RNA and so forth. This RNA also codes for the structural proteins of the virion (because the RdRP somehow forms shorter strands of RNA, called sub-genomic RNAs, specific to the making of those proteins by the hijacked ribosomes), so enabling the spread of the virus.

Jacinta: The key, the video tells me, is in the name polymerase. That’s an enzyme that puts nucleotides together in long chains. Also, many ribosomes – there are thousands in our cells – are connected to the cell membrane and can help create new virions that can leave the cell in much the opposite way they entered, being packaged and then budded off. Through this hijacking process, one virion can come in, and any number of them can go out, and generally from the lung region. They’re naturally attacked by the immune system causing inflammation, possibly pneumonia and respiratory failure.

Canto: Yes and thanks to Dr Roger Seheult for all this, we hope we’re not misreading his work. He goes on to talk about the possibility of inhibiting this nasty polymerase, RdRP. We might talk about this, or not, in the next post.

References

Coronavirus update 32, with Dr Seheult – series of videos

https://www.economist.com/briefing/2020/03/12/understanding-sars-cov-2-and-the-drugs-that-might-lessen-its-power

The gene machine, by Venki Ramakrishnan

Written by stewart henderson

April 25, 2020 at 2:04 pm

the politics of Covid-19: the China problem

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the sharp rise, and gradual decline, of active cases in South Korea, from Worldometer

So far we have no treatment for Covid-19, and can only use non-pharmaceutical interventions (NPIs) to stop or slow its spread. Evidence from Wuhan has conclusively shown that stringent NPIs have been effective in this regard. Not only did the case rate fall sharply from early February (after rising sharply from December to the end of January), but the proportion of critical cases was substantially reduced over the whole period. While recent very low numbers reported from China are creating an understandable skepticism due to the Chinese government’s tight grip on information, experts generally agree that the Wuhan data is reliable.

Reducing the rate of transmission is the goal of NPIs. Once the transmission rate (Rt) is reduced to less than 1.0, cases will reduce, and this will show in the statistics (while taking account of an incubation period of roughly 5 days and laboratory confirmation). Analysis in this JAMA article of the Wuhan measures, which became increasing stringent over a two-month interval, and which analysts divided into five consecutive periods, suggests that the period 3 measures (strict travel restrictions, including automobile travel, and home quarantine) were the likely determining factors in Rt reduction. This analysis, however, conveniently chimes with the fact that the more severe period 4 and 5 restrictions, involving heavily policed physical distancing measures, central quarantining, and door-to-door, individual-to-individual screening, would not go down well in an open society. I don’t want to cast doubt on the article, but this is China we’re talking about, and there are all sorts of political sensitivities in dealing with this heavy-handed economic giant.

I’ve long been thinking about this, but a Sydney Morning Herald article I found on my twitter feed (I virtually never tweet but it’s a useful resource) has prompted me to explore a bit more. It’s about Taiwan.

Taiwan’s experience re Covid-19 is worth comparing to Australia’s as their overall population is the same as ours. For a while I’ve been perhaps complacently touting Australia’s success in keeping the numbers down – we’re now the world’s 29th in number of cases, compared to 18th a couple of weeks ago. But Taiwan shits on us in this respect – 388 cases compared to our 6313, 6 deaths compared to our 61. It ranks 98th out of the countries and regions on Worldometer’s list.

The SMH article is essentially an interview with Professor Su Ih-Jen, the infectious diseases expert responsible for Taiwan’s response to Covid-19. He explains that this response, probably the most successful of any country, is all about Taiwan’s mistrust of China. The relationship between the two countries is about as bad as it can get, with China using its power internationally to stifle Taiwan’s voice in international forums such as the World Health Organisation. China has never recognised Taiwan’s nationhood, and is seen as an ever-present danger by the Taiwanese. So when word spread about the outbreak in Wuhan in December, Taiwanese experts assumed the worst and acted quickly, imposing quarantines and travel bans from China. The country had learned lessons from the first SARS outbreak, also from China, and substantially increased their numbers of ventilators and hospital beds. And have spent the past 17 years literally rehearsing for this new outbreak.

So while Taiwan’s success can’t be measured in any precise way in terms of its relationship to China, it has undoubtedly been a major factor. It’s worth considering in terms of other states influenced by the CCP. Hong Kong, for example, has a population of some 7.5 million, with obviously a very high population density. That’s somewhere between a third and a quarter of Australia’s population, yet it has less than a sixth of our confirmed cases – and we would be one of the most successful countries in containing the outbreak, by any measure. I hardly need to go into Hong Kong’s somewhat perilous relationship to China, but it’s worth comparing Hong Kong, with its 4 deaths so far, to New York State, the USA’s most hard-hit region, which has suffered over 10,000 deaths. That state has about 2.5 times the population of Hong Kong. It’s of course possible that there’s been suppression of data in Hong Kong, but it’s more likely that its preparedness, given its proximity to and intense suspicion of its powerful neighbour, provides a better understanding of its success.

A more complex case is that of South Korea. Having recently read a potted history of Korea, I’m now an expert haha. Korea, like Japan, has been massively influenced historically by Chinese culture, and generally recognises its debt. Of course there have been tensions, and battles, between the two nations, but they have generally been in uneasy alliance for centuries. Koreans adopted a variant of Chinese writing for their language, until the Hangul alphabetic script became popular in the 17th and 18th centuries. China is South Korea’s largest trading partner by far. It’s one of few countries that can boast a surplus in its trade with the economic giant. Tourism both to and from China has always been very popular, though the South Korean government introduced measures to reduce the flow of Chinese tourism in 2017. In the early days of Covid-19 reporting, South Korea was often mentioned as one of the most, if not the most, affected/infected nations outside of China. That has since changed dramatically, with the country receiving sometimes grudging, and certainly qualified, praise for its response. It developed effective testing kits in a matter of days, and is now exporting them to the world. Its rapid mobilisation of all government departments, its widespread testing of asymptomatic subjects, its quarantine measures, have been generally seen as exemplary. It seems South Korea has also learned from the SARS outbreak in 2003, though its late recognition of the dangers has sadly cost lives. Could this be because it was too trusting of China’s first muted reports of the virus? And couldn’t it be said that South Korea’s eventual forceful response, regarded as overly intrusive by some westerners, owed something to that of its largest trading partner?

So neighbourhood politics have definitely played a role in how the response to Covid-19 has played out in Hong Kong, Taiwan and South Korea, though the details are necessarily fuzzy. It’s also surely the case that complacency, even exceptionalism, in those regions far from what has been deemed the epicentre, has been very costly. In those regions, alertness about, and full preparedness for, the dangers of viral pandemics in general, setting aside China, should be the major lesson.

References

https://jamanetwork.com/journals/jama/fullarticle/2764656

https://www.worldometers.info/coronavirus/country/south-korea/

https://www.worldometers.info/coronavirus/country/china-hong-kong-sar/

https://www.worldometers.info/coronavirus/country/taiwan/

https://www.worldometers.info/coronavirus/country/us/

A brief history of Korea, by Michael Seth, 2019

https://en.wikipedia.org/wiki/Tourism_in_South_Korea

https://www.theguardian.com/commentisfree/2020/mar/20/south-korea-rapid-intrusive-measures-covid-19

https://www.sciencemag.org/news/2020/04/suppress-and-lift-hong-kong-and-singapore-say-they-have-coronavirus-strategy-works

Written by stewart henderson

April 14, 2020 at 12:13 pm

2019-nCoV: where does it come from?

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whether or not they led to 2019-nCoV in humans, leave pangolins alone

As mentioned previously, there are lots of coronaviruses. The four most commonly found in humans have these memorable names: 229E, NL63, OC43 and HKU1. These are humanly-borne viruses that seem to be more interested in increasing spread than increasing pathogenicity. We seem to have developed enough of an immunity from these common coronaviruses for them not to be a major problem. It’s perhaps the new strains that jump from bats to humans via an intermediate species – civets in the case of SARS, dromedary camels (probably) in the case of MERS – that are most likely to be pathogenic. Researchers are on the hunt for the intermediate carrier in the case of 2019-nCoV. Snakes were first suggested, but this has now been dismissed. The most recent candidate has been the pangolin, after research from the South China Agricultural University on the genome sequences of pangolin viruses found them to be 99 percent identical to those in coronavirus patients, but this is unpublished, unverified data at present.

Civets, pangolins? These are just some of the more or less exotic wild animals that some Chinese people like to consume or use for ‘medicinal’ purposes. Traditional Chinese medicine, aka medicine that doesn’t work, has a lot to answer for. Health experts are now recommending that the Chinese government clamp down on this practice. The presence of these creatures in open Chinese markets is disturbing. A prohibition was apparently put in place by the Chinese government just last month, a matter of shutting the stable door, but how well this will be enforced is a question.

Civet – harmless purveyor of SARS, and forget the coffee hype

Over the past 24 hours I’ve been coughing up a storm, and I’m due to work tomorrow. Medications are reducing the inflammation, and I note that wearing a common or garden surgical mask, which we see everywhere now, will not help. To quote from Live Science:

Coronaviruses can be transmitted between humans through respiratory droplets that infected people expel when they breathe, cough or sneeze. A typical surgical mask cannot block out the viral particles contained in these droplets, but simple measures — such as washing your hands, disinfecting frequently touched surfaces and objects, and avoiding touching your face, eyes and mouth — can greatly lower your risk of infection.

Of course I don’t have such a virus, and there are no known cases of it in Australia, though at least five Australians on a cruise ship off Japan have been confirmed as having contracted it. But as to surgical masks, the point is that viruses are much smaller than bacteria (on average about 1000 times smaller). They’re not cells, with their full complement of DNA, but strands of nucleic acid (DNA or RNA) encased within protein. They’re parasitic on hosts, unlike bacteria, and they’re generally pathogenic – we don’t have ‘good’ viruses as we have good bacteria. They can live outside of hosts for a limited period of time – hence the need for hand-washing and general cleanliness. Viruses in general may take a variety of shapes and sizes, ranging from the recently-identified DNA-based pandoraviruses at 1000 or so nanometres (1 micrometer) down to 20 nanometres or less. As to coronaviruses in particular (the largest of the RNA viruses) their structure and their ‘spike proteins’ will be glanced at in the next post.

References

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5457962/

https://www.thoughtco.com/differences-between-bacteria-and-viruses-4070311

https://www.sciencealert.com/the-pangolin-is-now-a-suspect-in-the-coronavirus-outbreak

https://www.livescience.com/face-mask-new-coronavirus.html

Written by stewart henderson

February 9, 2020 at 12:27 pm

coronavirus – a journey begins

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this is an electron micrograph of 2019-nCoV – ref JOHN NICHOLLS, LEO POON AND MALIK PEIRIS/THE UNIVERSITY OF HONG KONG. The cell is infected with the virus (the little black dots), which migrates to the cell surface and is released

Lots of information and disinformation around the recent outbreak of coronavirus, and my own occasional workplace, a college that teaches academic English to overseas, predominantly Chinese students, is naturally affected by the precautionary procedures and the possibly OTT concern.

This is a new strain of coronavirus, first detected late in 2019. It hasn’t been given a specific name, as far as I’m aware (apart from 2019-nCoV,  which I doubt will catch on) so lay people tend to think this is the one and only coronavirus, since most have never heard the term before. These viruses are zoonotic, transmitted between animals, from bats to humans. My interest is most personal, because when I read that the signs are ‘respiratory symptoms, fever, cough, shortness of breath and breathing difficulties’, I recognise my life over the past several years. I wouldn’t go as far as to say I have a fever, but all the other signs are just features of my life I’ve become inured to over time. I’m reluctant to even talk to people lest my voice catch in my throat and I have to give myself up to hideous throat-clearing, which I do scores of times a day. I’m also afraid to get too close as I assume my breath smells like rotten meat. I should probably wear a face mask at all times (hard to get one for love or money at this point). My condition has been diagnosed as bronchiectasis, possibly contracted in childhood, but I’m fairly sure it was exacerbated by a very severe bout of gastro-enteritis in the late eighties, which left me bed-ridden for several days, too weak to even get to the toilet. When I eventually recovered enough to drag myself to the doctor, she arranged for me to go to the hospital next door for blood tests. It was unspoken but obvious to me she thought I might have AIDS, which I knew was impossible given my non-existent sex life and drug habits. It seems to me, but I might be wrong, that my life of coughing, sniffling and raucus throat-clearing took off from that time.

All this by way of explaining why these types of illness catch my attention. WHO advice is for people to, inter alia, wash hands regularly, cook meat and eggs thoroughly, and keep clear of coughy-wheezy-sneezy people like me. 

Coronaviruses are RNA viruses with a long genome, longer than any other RNA virus. According to Sciencealert they’re so called because of the crown-shaped set of sugar-proteins ‘that projects from the envelope surrounding the particle’. This one is causing perhaps a larger panic than is warranted, when you compare its fatalities (and the numbers should be treated with skepticism at this stage) with those associated with regular flu season. Of course, the difference is that this coronavirus is largely unknown, in comparison to seasonal flu, and fear and wariness of the unknown is something naturally ‘programmed’ into us by evolution.  

There’s an awful lot to be said about this topic, biochemically, so I’ll write a number of posts about it. It’s not only of great interest to me personally, but of course it fits with my recent writings on DNA and its relations, including RNA of course, and to a lesser extent epigenetics. I’m becoming increasingly fascinated by biochemistry so it should be an enjoyable, informative journey – for me at least.

References

Cases of the new coronavirus hint at the disease’s severity, symptoms and spread

Updated: Your most urgent questions about the new coronavirus

https://www.who.int/health-topics/coronavirus

Written by stewart henderson

February 8, 2020 at 10:57 am

Posted in coronavirus, health, RNA, viruses

Tagged with , , ,