Lockdown diaries - COVID-19 matters!

[Resistance]

Yh

I know let's take everyone, put us in a line in front of a machine gun, but

we will use a bind person as the gunner. We all know she will get some and miss some, but hey.

Rightio then let's all line up shall we.

The world is standing in line and the those that endorsed the experimentation and the "accidental release is behind the gun. Eish!

 

[Intuthu Kagesi]

Interesting thoughts
"Shouldn't we all just get exposed and get it over with" ... It's mutating, so I'm not convinced that this would help, (not unlike flu in many ways. Then you would get the first infection which prepares you for the second mutation and infection and so and so on but I'm not a scientific calculator.
Now when you get it it's like going straight to the 5th mutation and your body is in shock because it wasn't prepared.
Almost like going from MTL from a pod to the expromizer v5. And then you can't wick it

..
It didn't reduce the risk of transmission to those that were protected and still got it. This thing was designed to take people out. So whether you have a mask on and sanitize, your still getting it if you're high risk.

I think @Feliks Karp post above answered this succinctly

 

[Grand Guru]

I shall remind you of what happened when the UK government decided to let the virus spread in rhe beginning of the pandemic in order to quickly reach herd immunity... it was a massacre.

 

[Adephi]

I shall remind you of what happened when the UK government decided to let the virus spread in rhe beginning of the pandemic in order to quickly reach herd immunity... it was a massacre.

Even Sweden didn't end up too great after they attempted the heard immunity strategy.

 

[Resistance]

The estimate of people getting recurring symptoms months down the line is in the 70% range, if you want permanent CNS damage and vascular damage, sure catching it would be a good idea. There is no such thing as natural herd immunity with these kinds of things, please get this idea out and in the trash. Stuff like the black plague quietened down because there were people with random gene mutations that did not allow it to replicate, and it killed off too many vectors before it could carry on circulating, but even that is still around.

There are a few reasons people get it twice.

Their body does not produce enough of a immune response, which in time wanes, this is dependent on different factors, point of infection, initial viral load, own physiology as well as the strain. The initial strain doesn't replicate as quickly in everyone as the new variants do, so this also won't produce as strong as an immune response, allowing for the new strain to replicate and overload the body quicker. Which is why they know that the vaccine response will pick up the new strain but are still looking if the vaccine response is strong enough to completely stop it.

Masks as stated many times are only about 70% effective at keeping the particles out IF USED CORRECTLY but 90% at keeping them in if you are sick. The masks aren't failing, the improper use of masks is failing, people are simply not wearing them correctly, cross infecting them etc etc. Washing hands/sanitizer? I've watched hundreds of people get it on their hands and do a quick rub, it's honestly as though no one has ever been taught how to wash their hands. Literally everyone I know personally who got it, got it from breaking protocol, dinner parties, gym. etc etc

There is also the fact that eyes are still uncovered, there are almost 0 pathogens that cannot make their way in to your body through your eyes.


Literally the only reason people are still contracting it is because they are mucking about.

I think @Feliks Karp post above answered this succinctly

Even Sweden didn't end up too great after they attempted the heard immunity strategy.

I shall remind you of what happened when the UK government decided to let the virus spread in rhe beginning of the pandemic in order to quickly reach herd immunity... it was a massacre.

So I'm the guy that asks the questions nobody wants to ask, but this time you have answered your own questions.
Now tell me how the vaccine would make things better for any of you if this covid19 virus mutates at the rate mentioned above. (Read through the answers again) plus all the other factors. One being no two people are alike and this "Thing" affects everyone differently. That means scientifically we all need a personalised vaccine.

 

[Resistance]

Or even better a mutating vaccine that mutates as the infection differs.
Sometimes the answers are right Infront of all of us but we refuse to acknowledge the fact that we have those answers.

+1on a vaccine
Still not for me thanks!

 

[Grand Guru]

@Resistance my friend. The vaccines are effective at 94% at best. They are not going to prevent every immunized person from getting the infection and in those who get the infection they are not going to prevent severe forms in every case. Furthermore, they are not without potential side effects some of which may be serious and I can go and on.... The thing is they are the best weapon we have to stop the progression, contain and maybe evict the virus completely. The idea is that we don’t need 100% effectiveness nor do we need 100% of the population immunized. We simply need 2 out of every 3 people having some immunity so that the chances of someone who had no exposure to the virus to meet someone like himself are less!
P.S vaccines are pieces of dead virus or something similar that induce an immune response by our immune system. They do not replicate neither do they mutate.

 

[Resistance]

@Resistance my friend. The vaccines are effective at 94% at best. They are not going to prevent every immunized person from getting the infection and in those who get the infection they are not going to prevent severe forms in every case. Furthermore, they are not without potential side effects some of which may be serious and I can go and on.... The thing is they are the best weapon we have to stop the progression, contain and maybe evict the virus completely. The idea is that we don’t need 100% effectiveness nor do we need 100% of the population immunized. We simply need 2 out of every 3 people having some immunity so that the chances of someone who had no exposure to the virus to meet someone like himself are less!
P.S vaccines are pieces of dead virus or something similar that induce an immune response by our immune system. They do not replicate neither do they mutate.

Were on the same page @Grand Guru .
Say I'm likely one of the 6percent that the vaccine does not protect or has no possitive effect to it. Then where does that place me.
I also agree that the vaccine does not replicate neither mutate, but the covid19 virus does. That's what they speak about on the news most of the day. (Unless this is also propaganda)
There's too many variables and I don't like that. So science is a good thing ,but I put my faith in God.

 

[Feliks Karp]

@Resistance my friend. The vaccines are effective at 94% at best. They are not going to prevent every immunized person from getting the infection and in those who get the infection they are not going to prevent severe forms in every case. Furthermore, they are not without potential side effects some of which may be serious and I can go and on.... The thing is they are the best weapon we have to stop the progression, contain and maybe evict the virus completely. The idea is that we don’t need 100% effectiveness nor do we need 100% of the population immunized. We simply need 2 out of every 3 people having some immunity so that the chances of someone who had no exposure to the virus to meet someone like himself are less!
P.S vaccines are pieces of dead virus or something similar that induce an immune response by our immune system. They do not replicate neither do they mutate.

In fact the newer ones are not even de-activated virus proteins, that are simply spike proteins replicated via a short period by your body, the same technology which they have used to make major leaps now in an MS vaccine (so this virus may have even helped us in many regards).

@Resistance

A virus has the chance to mutate EVERY replication, a virus can ONLY replicate in a host cell, so we stop host cells being infected, way less mutations. And despite the mild overlap between old wives tales and science, getting one strain DOES NOT make you stronger against another, that is not the reason we die less to flu these days, we die less because A. Vaccines B. Medical advancements (which are actually currently living in a major spike there of) and C. If a virus kills a host quickly it does not spread to enough hosts to spread as wide, so currently weaker flu strains are dominant because it allows them to spread.

There are a lot of variables, but that's where masks, cleanliness, and vaccines come in, you reduce the variables, and handle the risk.

 

[Resistance]

In fact the newer ones are not even de-activated virus proteins, that are simply spike proteins replicated via a short period by your body, the same technology which they have used to make major leaps now in an MS vaccine (so this virus may have even helped us in many regards).

@Resistance

A virus has the chance to mutate EVERY replication, a virus can ONLY replicate in a host cell, so we stop host cells being infected, way less mutations. And despite the mild overlap between old wives tales and science, getting one strain DOES NOT make you stronger against another, that is not the reason we die less to flu these days, we die less because A. Vaccines B. Medical advancements (which are actually currently living in a major spike there of) and C. If a virus kills a host quickly it does not spread to enough hosts to spread as wide, so currently weaker flu strains are dominant because it allows them to spread.

There are a lot of variables, but that's where masks, cleanliness, and vaccines come in, you reduce the variables, and handle the risk.

"between old wives tales and science, getting one strain DOES NOT make you stronger against another, that is not the reason we die less to flu these days, we die less because A. Vaccines B. Medical advancements (which are actually currently living in a major spike there of) and C. If a virus kills a host quickly it does not spread to enough hosts to spread as wide, so currently weaker flu strains are dominant because it allows them to spread."
This is one of the the I use the term I reserved earlier. I told you so!

 

[Resistance]

"between old wives tales and science, getting one strain DOES NOT make you stronger against another, that is not the reason we die less to flu these days, we die less because A. Vaccines B. Medical advancements (which are actually currently living in a major spike there of) and C. If a virus kills a host quickly it does not spread to enough hosts to spread as wide, so currently weaker flu strains are dominant because it allows them to spread."
This is one of the the I use the term I reserved earlier. I told you so!

"days, we die less because A. Vaccines B. Medical advancements (which are actually currently living in a major spike there of) "
I beg to differ, but that's another argument.

 

[alex1501]

P.S vaccines are pieces of dead virus or something similar that induce an immune response by our immune system.

In fact the newer ones are not even de-activated virus proteins, that are simply spike proteins replicated via a short period by your body, the same technology which they have used to make major leaps now in an MS vaccine (so this virus may have even helped us in many regards).

"Pieces of dead virus" and "spike proteins", really?

Oxford/AstraZeneca (to be distributed locally)
https://clinicaltrials.gov/ct2/show/NCT04516746

"Estimated Study completion date: February 21, 2023" (incomplete)
Main Biological ingredient AZD12222
"AZD12222 is a recombinant replication-defective chimpanzee adenovirus expressing the SARS-CoV-2-5 surface glycoprotein."

Used to deliver DNA payload directly to your cell nucleus.

To make it easier, here with pictures:

How the Oxford-AstraZeneca Vaccine Works

https://www.nytimes.com/interactive/2020/health/oxford-astrazeneca-covid-19-vaccine.html

Any ideas about how many things can go wrong here?

 

[Feliks Karp]

"Pieces of dead virus" and "spike proteins", really?

Oxford/AstraZeneca (to be distributed locally)
https://clinicaltrials.gov/ct2/show/NCT04516746

"Estimated Study completion date: February 21, 2023" (incomplete)
Main Biological ingredient AZD12222
"AZD12222 is a recombinant replication-defective chimpanzee adenovirus expressing the SARS-CoV-2-5 surface glycoprotein."

Used to deliver DNA payload directly to your cell nucleus.

To make it easier, here with pictures:

How the Oxford-AstraZeneca Vaccine Works

https://www.nytimes.com/interactive/2020/health/oxford-astrazeneca-covid-19-vaccine.html

Any ideas about how many things can go wrong here?

You realise a surface glycoprotein is a spike protein? You realise the delivery system is replication-defective, literally says that there in your post. Never mind that this is ONE delivery system, the other two contenders are very new and very groundbreaking, which actually GASP make your body replicate the spike protein (which does absolutely sweet **** all on its own but give your body a licence plate to look for).

I think the problem here is your understanding of this science is "easy", you are getting angry about things you do not understand. In fact that's more and more of what I see in this thread. So I'm actually going to withdraw in future on trying to educate people here.

 

[Resistance]

You realise a surface glycoprotein is a spike protein? You realise the delivery system is replication-defective, literally says that there in your post. Never mind that this is ONE delivery system, the other two contenders are very new and very groundbreaking, which actually GASP make your body replicate the spike protein (which does absolutely sweet **** all on its own but give your body a licence plate to look for).

I think the problem here is your understanding of this science is "easy", you are getting angry about things you do not understand. In fact that's more and more of what I see in this thread. So I'm actually going to withdraw in future on trying to educate people here.

If you're not getting angry then why are you leaving? We are trying to understand why you are pushing for the vaccine. Please stay and educate us so we can understand as well and maybe see it from your point of view.
Ps. still not interested in a vaccine (for me) you can go forth in your quest to be vaccinated.

 

[Resistance]

You realise a surface glycoprotein is a spike protein? You realise the delivery system is replication-defective, literally says that there in your post. Never mind that this is ONE delivery system, the other two contenders are very new and very groundbreaking, which actually GASP make your body replicate the spike protein (which does absolutely sweet **** all on its own but give your body a licence plate to look for).

I think the problem here is your understanding of this science is "easy", you are getting angry about things you do not understand. In fact that's more and more of what I see in this thread. So I'm actually going to withdraw in future on trying to educate people here.

Journal of Molecular Modeling
Nature Publishing Group
Reasoning of spike glycoproteins being more vulnerable to mutations among 158 coronavirus proteins from different species
Guang Wu and Shaomin Yan

Additional article information

Associated Data
Supplementary Materials
Abstract
In this study, we used the probabilistic models developed by us over the last several years to analyze 158 proteins from coronaviruses in order to determine which protein is more vulnerable to mutations. The results provide three lines of evidence suggesting that the spike glycoprotein is different from the other coronavirus proteins: (1) the spike glycoprotein is more sensitive to mutations, this is the current state of the spike glycoprotein, (2) the spike glycoprotein has undergone more mutations in the past, this is the history of spike glycoprotein, and (3) the spike glycoprotein has a bigger potential towards future mutations, this is the future of spike glycoprotein. Furthermore, this study gives a clue on the species susceptibility regarding different proteins.

Figure Predictable and unpredictable portions in coronavirus proteins. The data are presented as median with interquartile range. * the predictable and unpredictable portions in spike glycoprotein group are statistically different from any other protein groups at p<0.05 level, except for hemagglutinin-esterase precursor group. # the predictable and unpredictable portions in spike glycoprotein group are statistically different from hemagglutinin-esterase precursor, membrane protein and nucleocapsid protein groups at p<0.05 level. † the predictable and unpredictable portions in spike glycoprotein group are statistically different from hemagglutinin-esterase precursor, and membrane protein groups at p<0.05 level.

Electronic Supplementary Material is available for this article if you access the article at http://dx.doi.org/10.1007/s00894-004-0210-0.

Keywords: Coronavirus, Protein, Probability, SARS
Introduction
With the occurrence of new cases of severe acute respiratory syndrome (SARS), the prognosis of a possible return of SARS in the near future is coming true. Also hypothesis that the new SARS cases could be somewhat different from the previous SARS cases in possible mutated forms appears to be true. Accumulating evidence shows that there are mutations in the SARS-related coronavirus (SARS-CoV), [1, 2] which may lead to difficulties in diagnosis, treatment, and prevention.

The SARS-CoV is an enveloped RNA virus. Naturally, we would expect that the different components in human SARS-CoV would have different sensitivities to mutation, therefore it would minimize the difficulties in identification of SARS-CoV and facilitate diagnosis, treatment and prevention of SARS if we could identify which component of human SARS-CoV is most subject to mutations. Doubtlessly we should not limit ourselves to sole SARS-CoV, not only because many species carry coronaviruses [3, 4], but also, more importantly, because the coronavirus from civets is likely to be the source of SARS [5].

Among various components in coronavirus, we are more interested in the proteins, because over the last several years we have developed three models to analyze the protein primary structure (for a review, see [6]), including the proteins from SARS-CoV [7, 8]. In general, our first model can classify a protein into the randomly predictable and unpredictable portions, and our findings demonstrate that the unpredictable portion is more sensitive to mutations than the predictable one. Thus, we can find which protein is more vulnerable to mutations by comparing the unpredictable portion with the predictable one among proteins.

So far the envelope protein, hemagglutinin-esterase precursor, membrane glycoprotein, nonstructural protein, nucleocapsid protein, spike glycoprotein, replicase polyprotein and hypothetical proteins have been identified in coronavirus [9–12]. These proteins have the following functions: the hemagglutinin-esterase is the major receptor determinant, binding to sialic acid-containing receptors on the host cell and penetrating of virus genome into host cell cytoplasm by fusion of virus and host cell membranes. Both the envelope and membrane glycoproteins are components of the viral envelope that play a central role in virus morphogenesis and assembly via its interactions with other viral proteins. The nonstructural proteins mediate nuclear export of viral RNPs and bind RNA, thereby inhibiting host mRNA translation, and regulating viral pre-mRNA splicing and translation. The nucleocapsid protein is the major structural component of virons that associates with genomic RNA to form a helical nucleocapsid. The replicase polyprotein is a multifunctional protein containing the activities necessary for the transcription of negative stranded RNA, leader RNA, subgenomic mRNAs and progeny virion RNA as well as proteinases responsible for the cleavage of the polyprotein into functional products. The spike glycoprotein is responsible for both binding to receptors on host cells and for membrane fusion [13–21].

Currently, the sequences of 158 coronavirus proteins from different species have been documented. Each protein must have its own specific sensitivity to mutations otherwise the proteins would have the same ratio of mutations per amino acid sequences. However such an expectation has yet been found, it is therefore important to define which protein is more sensitive to mutations than the others. The aim of the present study is to discover which protein is more sensitive to mutations among 158 coronavirus proteins using the model developed by us over the last several years.

Materials and methods
The amino acid sequences of 158 coronavirus proteins were obtained from the Swiss-Prot databank [22]. These proteins are grouped as envelope proteins, hemagglutinin-esterase precursors, membrane glycoproteins, nonstructural proteins, nucleocapsid proteins, spike glycoproteins and others including replicase polyprotein and hypothetical proteins (for details, see Supplementary Material).

The detailed calculations of randomly predictable and unpredictable portions in proteins have already been published previously (for a review, see [6]). The calculations governed by the simple permutation principle [23] are described for the example of the spike glycoprotein from human SARS-CoV, which consists of 1,255 amino acids. As we know that an amino-acid pair in a protein is composed of any 20 kinds of amino acids, so theoretically there are 400 possible types of amino-acid pairs. In terms of amino-acid pairs, distinguishing proteins is different either in the numbers of possible types of amino-acid pairs or in the frequency of each type, or both.

Randomly predictable present type of amino-acid pair with predictable frequency
There are 39 arginines (R) and 96 serines (S) in spike glycoprotein from human SARS-CoV, the random frequency of the amino-acid pair “RS” is 3 (39/1,255×96/1,254×1,254=2.983). Actually we find three “RS‘’s in the spike glycoprotein, so the type of “RS” is present and its frequency is 3. In such a case, both the presence of type “RS” and its frequency are randomly predictable, and the difference between actual and predicted values is 0.

Randomly predictable present type of amino-acid pair with unpredictable frequency
There are 84 alanines (A) in the spike glycoprotein from human SARS-CoV. The frequency of random presence of “AA” is 6 (84/1,255×83/1,254×1,254=5.555). In fact “AA” appears ten times. Thus the presence of type “AA” is randomly predictable, but its frequency is randomly unpredictable, and the difference between actual and predicted values is 4.

Randomly unpredictable present type of amino-acid pair
There are 11 tryptophans (W) in the spike glycoprotein from human SARS-CoV, the frequency of random presence of “WR” is 0 (11/1,255×39/1,254×1,254=0.342), i.e. the type “WR” would not appear in the spike glycoprotein. However “WR” appears once in reality, so the presence of type “WR” is randomly unpredictable. Naturally its frequency is unpredictable too, and the difference between actual and predicted values is 1.

Randomly predictable absent type of amino-acid pair
The frequency of random presence of “RW” is 0 (39/1,255×11/1,254×1,254=0.342), i.e. the type “RW” would not appear in the spike glycoprotein, which is true in the real situation. This is the case that the absence of type “RW” with its frequency is randomly predictable, and the difference between actual and predicted values is 0.

Randomly unpredictable absent type of amino-acid pairs
There are 99 threonines (T) in the spike glycoprotein, the frequency of random presence of “RT” is 3 (39/1,255×99/1,254×1,254=3.076), i.e. there would be three “RT”s in the spike glycoprotein. However no “RT” is found, therefore the absence of “RT” from the spike glycoprotein is randomly unpredictable. Naturally its frequency is unpredictable too, and the difference between actual and predicted values is −3.

Statistics
With respect to actual and predicted values in a single protein, the statistical inference is carried out as follows. Generally, each of 20 kinds of amino acids has a chance of 1/20 (p=0.05) to repeat once, and a type of amino-acid pair has the chance of 1/400 (p=0.0025) to repeat once. In case of the spike glycoprotein from human SARS-CoV, there are 99 Ts, the most abundant amino acid, and 11 Ws, the least abundant amino acid. If the first amino acid is “T”, then the chance of the second amino acid to be “T” is 98/1,254 (p=0.078>0.05), if the first amino acid is “W”, then the chance of the second amino acid to be “W” is 10/1,254 (p=0.008<0.01). Thus, the chance of first “TT” is 99/1,255×98/1,254 (p=0.0062<0.01), and the chance of second “TT” is 97/1,253×96/1,252 (p=0.0059<0.01). If we consider the lowest occurring amino acids “W”, the chance of first “WW” is 11/1,255×10/1,254 (p=0.00007<0.001), and the chance of second “WW” is 9/1,253×8/1,252 (p=0.00005<0.001). Clearly, the probability is less than 0.05 if the difference between actual and predicted values is equal to or larger than 1.

With respect to the comparisons among proteins, the statistical inference is conducted as follows. All the data are examined by the Kolmogorov–Smirnov test to determine their distribution properties. For normal distributions, the data are presented as mean ± SD. For non-normal distributions, the data are presented as median with interquartile range. Outliers are detected according to Healy’s method [24]. The one-way ANOVA and the Friedman ANOVA rank tests are used for parametric and non-parametric tests, respectively, followed by comparison tests. SigmaStat for Windows (SPSS Inc, 1992–2003) is used to perform all the statistical tests, and the p<0.05 is considered statistically significant.

Results
After such calculations, the amino-acid pairs in a protein are classified into randomly predictable and unpredictable portions. By comparing the percentages of predictable and unpredictable portions among different proteins, we can find which protein has a larger unpredictable portion than others. Consequently this protein is more sensitive to mutations according to our previous studies [25–32].

Figure 1 shows the predictable and unpredictable portions in coronavirus proteins. This figure can be read as follows. The length of each bar presents 100%, which is located at both unpredictable and predictable sites separated by dotted line. For example, the unfilled bar in spike glycoprotein group presents the absent types, which are composed of 19.70% randomly predictable portion with interquartile range from 16.67 to 26.89% (right panel) and 80.30% randomly unpredictable portion with interquartile range from 73.11 to 83.33% (left panel). The statistical inference in Fig. 1 as well as Fig. 2 is conducted by using the ANOVA test to detect whether or not there is a difference among different proteins in a panel followed by a comparison test. For example, regarding the absent type in Fig. 1, at first we use the Friedman ANOVA rank test whether or not there is a difference among different protein groups. Taking three bars in Fig. 1 into account, the spike glycoproteins have a larger unpredictable portion than others. These results suggest that the spike glycoprotein is more sensitive to mutations than other coronavirus proteins.


Fig. 1
Predictable and unpredictable portions in coronavirus proteins. The data are presented as median with interquartile range. * the predictable and unpredictable portions in spike glycoprotein group are statistically different from any other protein groups ...

Fig. 2
Percent of unpredictable types and frequencies with respect to whether the actual value is larger or smaller than the predicted value in coronavirus proteins. The data are presented as mean ± SD. * the percents of unpredictable ...
Although different proteins have different types of unpredictable absent amino-acid pairs, some types are absent from all members of a group of proteins. For example, the amino-acid pair “WI” is absent from all 27 spike glycoproteins no matter which kind of species or strain (Table 1).


Table 1
Unpredictable absent amino-acid pairs that disappear from a group of proteins
Thereafter, we are particularly interested in the unpredictable portions (left panel in Fig. 1), because they are not engineered by randomness. As mentioned under Materials and methods, an unpredictable portion includes the unpredictable types and predictable types with unpredictable frequency, which can be presented as the actual values either larger or smaller than its predicted values. Our previous studies reveal that the unpredictable types whose actual value is larger than its predicted value are highly likely to be targeted by mutations, whereas the unpredictable types whose actual value is smaller than its predicted value are highly likely to be formed after mutations [25–33].

Figure 2 illustrates the percentage of unpredictable types and frequencies with respect to whether the actual value is larger or smaller than its predicted value in coronavirus proteins. Technically Fig. 2 is a subset of Fig. 1 obtained by classifying the data in the left panel of Fig. 1 into two criteria, i.e., the actual value is larger than the predicted value, or vice versa. In view of the unpredictable portion whose actual value is smaller than its predicted value (left panel), the spike glycoproteins have the largest percentages in both unpredictable type and frequency among different coronavirus proteins. Whereas in view of the unpredictable portion whose actual value is larger than its predicted value (right panel), the spike glucoprotein group reveals a larger percentage of unpredictable type accompanied by a smaller percentage of unpredictable frequency. This means that the spike glycoprotein might have undergone more mutations in the past than others.

Subsequently, we are still more interested in the magnitude of difference between the actual and predicted values because our previous studies show that the larger the difference between actual and predicted values, the bigger the potential towards future mutations [25–33].

Figure 3 displays the magnitude of difference between actual and predicted values in coronavirus proteins. It can be seen that the difference between actual and predicted values is larger in the spike glycoprotein group than in others. This implies that the spike glycoproteins have a high potential for future mutations.


Fig. 3
Magnitude of difference between actual and predicted values in coronavirus proteins. The data are presented as mean ± SD. * indicates the difference between actual and predicted values in spike glycoprotein group is statistically ...
In addition, the difference between the actual and predicted values can tell us which species is more subject to mutations if we arrange the number of amino-acid pairs with respect to the difference between the actual and predicted values in each group of proteins from different species.

Figures 4, ,5,5, ,6,6, ,7,7, ,8,8, ,99 and and1010 show the difference between the actual and predicted values in each group of proteins from different species. The scale of the vertical axes in Figs. 4, ,5,5, ,6,6, ,7,7, ,8,8, ,99 and and1010 is shown logarithmically in order to emphasize the amino-acid pairs with large differences between the actual and predicted values. Due to the limitation of the graphic software, the filled forms are duplicated in one or two bars. However the data used in these figures can be found in the Supplementary Material. These figures can be understood as follows, the bars at two extremes along the horizontal axis present the amino-acid pairs sensitive to mutations, because our previous studies have shown that the larger the difference between actual and predicted values is, the more sensitive to the mutations is [25–33]. By comparing the scales of horizontal axes from Figs. 4, ,5,5, ,6,6, ,7,7, ,8,8, ,99 and and10,10, we can see that the spike glycoproteins are more sensitive to mutations than other proteins because Fig. 9 has a largest scale for the horizontal axis. Still we can see which species is more sensitive to mutations in each figure. For instance, the human spike glycoprotein is more sensitive to mutation in Fig. 9.


Fig. 4
Number of amino-acid pairs in envelop proteins from different species with respect to the difference between their actual and predicted values. The data are presented as mean ± SD.

Fig. 5
Number of amino-acid pairs in hemagglutinin-esterase precursor proteins from different species with respect to the difference between their actual and predicted values. The data are presented as mean ± SD.

Fig. 6
Number of amino-acid pairs in membrane glycoproteins from different species with respect to the difference between their actual and predicted values. The data are presented as mean ± SD.

Fig. 7
Number of amino-acid pairs in nonstructural proteins from different species with respect to the difference between their actual and predicted values. The data are presented as mean ± SD.

Fig. 8
Number of amino-acid pairs in nucleocapsid proteins from different species with respect to the difference between their actual and predicted values. The data are presented as mean ± SD.

Fig. 9
Number of amino-acid pairs in spike glycoproteins from different species with respect to the difference between their actual and predicted values. The data are presented as mean ± SD.

Fig. 10
Number of amino-acid pairs in other proteins from different species with respect to the difference between their actual and predicted values. The data are presented as mean ± SD.
Discussion
Without clearly identifying the source of SARS-CoV, its fast-spreading process, and its mutations, the battle with SARS is unlikely to be finished soon, therefore sooner or later we would expect to see new mutated forms of SARS-CoV. In such a case the determination of vulnerable proteins in SARS-CoV is important and pressing.

The coronaviruses exhibit considerable serologic and sequence variation, with the most extreme variability being within S genes [3]. Variant spike glycoproteins [34] are now known to impact pathogenic outcome [15, 35–37].

This study provides three lines of evidence that suggest that the spike glycoprotein is different from the others: (1) the spike glycoprotein is more sensitive to mutations, this is the current state of spike glycoprotein, (2) the spike glycoprotein had experienced more mutations in the past, this is the history of spike glycoprotein, and (3) the spike glycoprotein has a bigger potential towards future mutations, this is the future of spike glycoprotein.

With respect to the first line of evidence, the argument is that the randomly unpredictable portion is larger in spike glycoproteins than in others (Fig. 1). If we compare the unpredictable portion in spike glycoproteins with the proteins we have studied in the past (columns I and II in Table 2, similar to the left panel in Fig. 1), we find that the unpredictable portion of the present types is statistically larger in spike glycoproteins than in others, and statistically similar in the unpredictable portion of the present frequencies. This suggests that the spike glycoprotein is not only more sensitive to mutations than other coronavirus proteins, but also more sensitive than the proteins in Table 2.


Table 2
Characteristics of the proteins that we have studied in the past
With respect to the second line of evidence, we find that the spike glycoprotein has a larger percentage of unpredictable types and frequencies whose actual values are smaller than the predicted values in Fig. 2. Actually, 172 mutations have currently been documented in coronavirus proteins, of which 153 occur in spike glycoproteins. This supports our argument that the spike glycoprotein has undergone more mutations in the past. Moreover, if we look at the nine proteins which have been documented with more mutations (column IX in Table 2), we find that the percentage of unpredictable type in spike glycoproteins is statistically similar to the proteins in Table 2 (columns III and IV in Table 2, similar to right panel in Fig. 2), but the difference regarding the percentage of unpredictable frequencies is statistical significant. This suggests that the intensity of mutations in spike glycoproteins is weaker than the first nine proteins listed in Table 2.

With respect to the third line of evidence, we find that the difference between actual and predicted values in spike glycoproteins is larger than in others (Fig. 3). Comparison with the first nine proteins in Table 2 (columns V, VI, VII and VIII in Table 2, similar to Fig. 3) shows that the difference between actual and predicted values is statistically larger in spike glycoproteins regarding unpredictable types and is statistically smaller regarding unpredictable frequency. This suggests that the spike glycoprotein still has more potential for mutations than the first nine proteins in Table 2.

For the species susceptibility, the vulnerability of species depends on the number of amino-acid pairs with the largest difference between actual and predicted values. Figures 4, ,5,5, ,6,6, ,7,7, ,8,8, ,99 and and1010 may, at least partly, highlight the species susceptibility. For example, why have so many mutations been found in the human spike glycoproteins?

Although it is obvious that an individual protein is different from the other proteins of a genome, our results quantitatively and systematically determine the difference between the spike and other proteins by comparing their predictable and unpredictable portions of amino-acid pairs. One may argue that it is also known that spike proteins interact with the host, the environment and the immune system and so their structure is particularly vulnerable to mutations both in the past and in the future and also regarding its specific phenotypic effects in the numerous interactions it is involved in. However we would like to argue that the host, the environment and the immune system are the external factors imposed on the spike proteins, while the internal factor in the spike proteins, which is particularly interesting to us, is the structure that can be partially explained by our random approach. In another study on the spike protein, we specifically discussed the spike proteins from three human coronaviruses classified with our approach and gave predictions of possible and potential mutation forms regarding the spike protein structure [7].

At this stage of study, it is still difficult to define the reason and to give a biological explanation to the results that the absent types in the spike protein behave differently from and opposed to other proteins, although we have discussed the biological explanation in the present types in rat monoamine oxidase B in the past [38]. However it is certain that the randomly unpredictable absent types should be deliberately eliminated from a protein rather than being self-organized and self-empowered. This is so because such an absence cannot be explained by randomness which suggests the least time- and energy-consuming.

In this study, we do not consider the situation that individual variation within the other protein groups could not in specific cases lead to similar values as observed for specific spike proteins. This is so because the individual variation within the other protein groups would lead to a mutated form of a protein, while this study deals with proteins without mutations. However, a mutated form of protein may lead its predictable and unpredictable portions to shift to similar values as observed for specific spike proteins. In the current form of this study, we cannot make any solid prediction from the present analysis for the behavior of individual proteins, but only observe an overall trend.

The medical implication is that the mutation sensibility in spike glycoprotein leads to the difficulties in producing vaccines that provide us with long-lasting protection against SARS. This finding can be correlated with hemagglutinin and neuraminidase from influenza A virus. Both hemagglutinin and neuraminidase are surface proteins, and subject to the pressure of the antibody and the selective pressure for the appearance of host cell variant with altered receptor binding specificity. Meanwhile the spike glycoprotein is responsible for both binding to receptors on host cells and for membrane fusion. In this viewpoint, the spike glyprotein is quite similar to hemagglutinin and neuraminidase.

The multiple sequence alignments are a phenomenological technique by comparing the similarity among proteins. The phenomenological analogy can be classified into at least three types. For the simplest example, we compare the letters that construct a word to guess the meaning of the word. Another type of phenomenological analogy is equivalent in physical laws, for example, Fick’s law and Kirchhoff’s law are equivalent to the law of conservation. The third type of phenomenological analogy is mathematically similar, for example, the transfer of energy, mass, heat and momentum can be described by using similar differential equations. [39, 40] In fact, what the multiple sequence alignments are doing is language similarity. On the other hand, our approach is a mechanism-driven technique by calculating the randomly predictable and unpredictable portions in a protein. Our approach is not a phenomenological tool, and is studying the internal power engineering the mutations. Multiple sequence alignments cannot predict the future, while our approach can predict the likelihood of future mutations. Technically, multiple sequence alignments need a large database for searching, while our approach needs a few data but a large amount of calculations. In general, multiple sequence alignments are the first step for the understanding of proteins, DNA, etc., and science must advance to seek other new techniques for the understanding of proteins, DNA, etc. However, our approach at this moment is only related to the primary structure, therefore it cannot give information on loop regions, as multiple sequence alignments also cannot. With respect to the evolutionary pressure, our approach is using the randomly unpredictable portion to account, as we argue that the randomly unpredictable portion should be deliberately developed through the evolutionary process. This is so because randomness suggests the least time- and energy-consuming to construct proteins.

In conclusion, our results suggest that the spike glycoproteins are more vulnerable to mutations among coronavirus proteins, however the chance of occurring of mutations would be less in spike glycoproteins than in highly-frequently-mutated proteins, e.g. the human p53 protein.

(Excel 47 KB)(46K, xls)


Acknowledgements
The authors wish to thank the anonymous referees for their insightful comments, which sharpen up the points presented in this study.

Article information
J Mol Model. 2005; 11(1): 8–16.
Published online 2004 Dec 9. doi: 10.1007/s00894-004-0210-0
PMCID: PMC7088192
PMID: 15592899
Guang Wu

and Shaomin Yan
Computational Mutation Project, DreamSciTech Consulting Co. Ltd., 301, Building 12, Nanyou A-zone, Jiannan Road, Shenzhen, Guangdong Province 518054 China
Guang Wu, Phone: +86-755-22029353, Email: moc.oohay@oahabihsilgnauggnoh.

Corresponding author.
Received 2004 Mar 18; Accepted 2004 Aug 30.
Copyright © Springer-Verlag 2004
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
This article has been cited by other articles in PMC.
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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7088192/

 

[Resistance]

Even Sweden didn't end up too great after they attempted the heard immunity strategy.

But they make great snuss and the best chocolate in the world. (Non subjective)

 

[Grand Guru]

 

[alex1501]

You realise a surface glycoprotein is a spike protein? You realise the delivery system is replication-defective, literally says that there in your post. Never mind that this is ONE delivery system, the other two contenders are very new and very groundbreaking, which actually GASP make your body replicate the spike protein (which does absolutely sweet **** all on its own but give your body a licence plate to look for).

I think the problem here is your understanding of this science is "easy", you are getting angry about things you do not understand. In fact that's more and more of what I see in this thread. So I'm actually going to withdraw in future on trying to educate people here.

What you don't realise is that you know nothing about me, but FYI when I made my first nitroglycerine and nearly caused a stroke to my chemistry teacher, yoy were still dangling around in your dady's balls. When I became a military chemist you turned 5, so your patronizing is unwarranted.
You absolutely have no idea about what I know and understand.
Back to the topic: that "ONE delivery system" is what is going to represent 95% of the distribution here in SA and there is not even one complete study available for it.

 

[Adephi]

What you don't realise is that you know nothing about me, but FYI when I made my first nitroglycerine and nearly caused a stroke to my chemistry teacher, yoy were still dangling around in your dady's balls. When I became a military chemist you turned 5, so your patronizing is unwarranted.
You absolutely have no idea about what I know and understand.
Back to the topic: that "ONE delivery system" is what is going to represent 95% of the distribution here in SA and there is not even one complete study available for it.

http://letmegooglethat.com/?q=one+delivery+system+vaccine

 

[alex1501]

http://letmegooglethat.com/?q=one+delivery+system+vaccine

Followed instructions to the letter, it wasn't easy but I made it. Still nothing, not a single complete trial and study of that AstraZeneca
thingy, but thanks for trying.

 

[Intuthu Kagesi]

You realise a surface glycoprotein is a spike protein? You realise the delivery system is replication-defective, literally says that there in your post. Never mind that this is ONE delivery system, the other two contenders are very new and very groundbreaking, which actually GASP make your body replicate the spike protein (which does absolutely sweet **** all on its own but give your body a licence plate to look for).

I think the problem here is your understanding of this science is "easy", you are getting angry about things you do not understand. In fact that's more and more of what I see in this thread. So I'm actually going to withdraw in future on trying to educate people here.

Please keep the education coming @Feliks Karp ... I get that most if not all of us are scared, as we don't currently have all the answers ... and let's not beat around the bush here ... Covid IS life threatening!

There's an old Engineering maxim that goes; "If it doesn't make sense, you don't have all the facts", and that is where our fears are based. so to reiterate ... Bring on the knowledge!

 

[Intuthu Kagesi]

But they make great snuss and the best chocolate in the world. (Non subjective)

Exactly! ... so let's give the person who does know more than us on the subject a chance to educate us ... and from where I sit, that seems to be @Feliks Karp

 

[Adephi]

Followed instructions to the letter, it wasn't easy but I made it. Still nothing, not a single complete trial and study of that AstraZeneca
thingy, but thanks for trying.

Do you honestly think any pharmaceutical company are just going to throw their recipe out on the internet? Thats kept secret like the ingredient list for Coca-Cola.

 

[alex1501]

Do you honestly think any pharmaceutical company are just going to throw their recipe out on the internet? Thats kept secret like the ingredient list for Coca-Cola.

Nope, but I'll wait fot this one https://clinicaltrials.gov/ct2/show/NCT04516746 to get completed and then I'll revaluate my position.

 

[Feliks Karp]

Exactly! ... so let's give the person who does know more than us on the subject a chance to educate us ... and from where I sit, that seems to be @Feliks Karp

I certainly do NOT know the most, but I'm not going to get in to arguments with people when they go off at me for stating a fact especially if they throw back a contradictory statement. And that seems to happen more often than not in this thread.