Thursday, April 22, 2021

SARS & Covid-19 Coronavirus

The blogger’s note:

There was a report from Reuters in May 11, 2020 (refer: https://www.reuters.com/article/uk-factcheck-coronavirus-patent-idUSKBN22M0SW) that a viral video claiming Covid-19 patent has existed for years and hinting to conspiracy is FALSE.

It was reported that those claims (dating back to at least 2006) falsely confuse the patents for Severe Acute Respiratory Syndrome (SARS) with COVID-19, the illness caused by the new coronavirus.  SARS is also part of the coronavirus family, but it stems from a different coronavirus strain and is a different disease to COVID-19.

SARS is caused by the severe acute respiratory syndrome coronavirus (SARS-CoV or SARS-CoV-1) strain. COVID-19 is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain. The similarity in the strains’ names and the fact both are in the coronavirus family may explain the confusion and widespread sharing of the false claim.

Dr. Rita Gregory, a chat group member, requested Dr. JB Lim to clarify as the patents seemed to refer to SARS virus and not the current Covid-19 coronavirus.

The following is the reply from Dr. Lim on 21/04/2021:


Thank you very much my dear Dr. Rita for your question.

First of all I am not an expert to tell you whether or not SARS-CoV-2 is exactly the same as Covid-19 because this needs the following study:

1. Sequencing by determining the order of the four chemical building blocks - called "bases" - that make up the DNA molecule as well as to analyze the transcriptome of gene expression patterns encoded within their RNA. 

2. Determining the size of the RNA fragments through electrophoresis on agarose, or poly- acrylamide gels, and the molecular size of their RNA. 

3. Examining the evolutionary relationships among the various corona viruses or phylogenetics. 

4. Comparing their morphology under an electron microscope. 

5. Comparing their degrees of infectivity among others. 

I wish I am able to study all these to tell you the differences. 

The only thing I can do now is search the literature done by other researchers, and from there use their data and findings through what I know in molecular biology and RNA / DNA genomic chemistry and their structural differences and my understanding in evolutionary biology / medicine to deduce my own inference.

Here’s what I know:


SARS-CoV-2 and Covid-19

 

The current Covid-19 pandemic is both a mutant strain and variant of the 2019-nCoV, now relabeled as SARS-CoV-2 that caused the severe acute respiratory syndrome in 2003.

Both have a phylogenetics lineage to the group of coronaviruses belonging to the coronaviridae family of the order nidovirales that include the beta-coronavirus under the Phylogenetic Tree of SARS-CoV-2.

SARS-CoV-2 is a Baltimore class IV positive-sense ssRNA virus and is thought to have zoonotic origins which scientists believe include the present Covid-19 virus.

In simple words, both SARS-CoV-2 and Covid-19 are cousins from the same coronaviridae family. 


SARS-CoV-2 and other coronaviruses are all cousins. There are of course other coronaviruses current, and yet to come from my understanding in Evolutionary Biology.

However, as far as I know, these coronaviruses that include alpha- and beta-corona viruses are more likely to infect other mammals, whereas gamma- and delta-coronaviruses tend to infect birds.

As far as I could gather from the literature there are currently 7 known human CoVs that are more likely to infect only humans.

These are namely, HCoV-NL63, HCoV-229E (both alphacoronaviruses), and HCoV-OC43, HCoV-HKU1, SARS-CoV, MERS-CoV, and SARS-CoV-2 (beta coronaviruses).

Hence my advice is to take great, great care for more pandemics under these groups of coronaviruses yet to come, is what I can foretell from what I know on evolutionary medicine. 

As far as the present knowledge available for us, SARS-CoV-2 shares the highest overall genome sequence similarity to the bat coronavirus RaTG13, but not the most deadly.

This said, the RBD (another strain of CoV) shares more sequence similarity with the pangolin coronavirus SARS-CoV (MP489/Guandong/2019), which binds to ACE2 receptors. This suggests evidence as far as I can understand of a recombination event in the evolution history of SARS-CoV-2 due to animal mixing before evolving to infect humans, and I am quite confident of this event from what I understand on the genomics of evolution.

Size-wise, all coronaviruses contain 26,000-32,000 bp genomes with a variable 6-11 open reading frames (ORFs), which encode non-structural proteins as well as structural proteins, namely the spike glycoprotein, a small envelope protein, matrix protein, and nucleocapsid protein which we are familiar with their chemistry.

This common denominator gives them all trillions of chances to rearrange their sequence to produce mutant strains and variants far beyond our comprehension for which none of any of our vaccine or vaccines we care to produce would be capable of challenging their evolutionary events (yet to come). 

In summary,

1. The SARS-CoV-2 is related to SARS-CoV, the virus that causes SARS, in addition to SARS-like bat CoVs (RaTG13/CoVZC45/CoVZCX21).

2. All binds to the ACE2 receptor due to their similar S domain genomic sequences.

3. Furthermore, a large proportion of SARS-CoV and SARS-CoV-2 genomes are identical. However, notable differences occur in key locations such as the absence of 8a protein and longer 8b protein in SARS-CoV-2.

4. In one analysis in the literature, there were 380 amino acid substitutions between SARS-CoV-2 and SARS/SARS-like viruses, specifically located in nsp2 & nsp3.

5. 6 substitutions were found in the RBD at amino acid location 357-528, with a further 4 substitutions in the C-terminus region of the S1 domain.

6. However, no substitutions were found in nsp7, nps13, E, M, and accessory proteins p6 and 8b.

This suggests that the differing RBD domain substitutions are probably behind the increased pathogenicity and transmissibility between SARS-CoV-2 and SARS-CoV. But we are still uncertain.

From what I can gather, SARS-CoV-2 possesses an intact open reading frame 8 without the 29-nt deletion found in a majority of human SARS-CoV.

Furthermore, SARS-CoV-2 contains a distinct proteolytically sensitive activation loop (polybasic furin cleavage site) at the S1-S2 junction that is not typically found in other human lineage beta coronaviruses.

However, this is a feature of several other animal and human coronaviruses, such as HKU1 (lineage A). Compared to SARS-CoV, the addition of such a cleavage site is thought to enhance cell-cell fusion.

Many studies have shown that the polybasic cleavage site in SARS-CoV-2 promotes cell-cell fusion and infectivity.

However, MERS-CoV diverges from SARS-CoV & SARS-CoV-2 at the RBD as MERS-CoV binds to DDP4.

Furthermore, encoded proteins pp1ab, pp1a, E, M, accessory protein 7a, and N genes vary considerably between SARS-CoV/CoV-2 genomes.

In simple language translated from RNA chemistry and molecular biology (sorry for all those languages), all these groups of coronaviruses are extremely dangerous with potentially very high pathogenicity yet to come to infect humans. This is my view.

My advice to everyone especially when we are old, is just take very extra care.

But best is to let God take over to cover us from His wrath. 

I hope this helps and thank you for your question, my dear former IMR colleague and friend Dr. Gregory Rita. 

 

Jb lim

---------------------

Later on Apr 22, 2021, Dr. JB Lim wrote further to provide a simplified summary on the differences between SARS-COV-2 and Covid-19 which had confused some chat group members as follows:


For the benefit of all readers, here’s what I mean in 6 steps:

1.   In simple language, both SARS-Covid 2 and Covid-19 are brother and sister from the same family. This family is called the “coronaviridae family”.

2.   SARS-Covid-2 which was born in 2003 was the brother which was far less aggressive, and current Covid-19 is his sister, born in 2019 and she is terribly aggressive.

3.   The entire family of SARS-CoV and other corona viruses are all cousins to each other.

4.   They also have other relatives too, whose names are: alpha- and beta-corona viruses, but these relatives are more likely to infect mammals than humans. 

5. On the terms “HCoV-NL63, HCoV-229E (both alphacoronaviruses), and HCoV-OC43, HCoV-HKU1, MERS-CoV, and SARS-CoV-2 (beta coronaviruses)”, these mean they all nephews, nieces, brother-in-laws and sister-in-laws of either SARS-CoV or Covid-19.

These additional members are quite new into the family, and they are yet to be evolved fully. Hence they can potentially be even more lethal and deadly than the current Covid-19 to humans, possibly in the near future just like Covid-19 is currently more deadly than her brother 16 year ago.    

6.   On the other descriptions here: “There were 380 amino acid substitutions between SARS-CoV-2 and SARS/SARS-like viruses, specifically located in nsp2 & nsp3 and 6 substitutions were found in the RBD at amino acid location 357-528, with a further 4 substitutions in the C-terminus region of the S1 domain...etc., etc.”

No. 6 are just jargons we use in DNA and RNA chemistry and in molecular biology / molecular medicine to describe the difference between SARS-CoV-2 and Covid-19 based on the location of their chemical components. Imagine them each having their own identity with houses (RNA) of their own. Each house has different types of rooms with their own locks and keys as amino-acids or protein located in different places.

These locks and keys can change positions or substituted in different locations when their houses and rooms are threatened, such as by vaccines, drugs or any hostile environments such as by heat and hand sanitizers containing alcohol, etc, etc. 

I hope these very simple analogies though not exactly as the technical terms used, serve as explanations in 6 steps that helps us understand.

Thank you for your patience trying to figure out. I am sorry for the confusion.


 Jb lim  

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