The
most devastating, catastrophic tragedy in the last centuries, which knocked on
the door around Dec 2019 (as claimed by Beijing) in Wuhan city of China has infected 152925596 people
worldwide and claimed at least 3208694 lives so far. And it keeps on growing
like Tsunami. However, there are a sufficient number of significant claims
which say that the current number could be reduced significantly if WHO and
China could have maintained transparency. The WHO is calling the
microbe novel coronavirus 2019-nCoV.
At a meeting in Geneva on
Jan 23, 2020, the organization stopped short of declaring a Public Health
Emergency of International Concern, but not declared it as Pandemic till
Jan 29, 2020. Nevertheless, the same WHO said, ‘Indian Covid variant’
found in 27 other countries on Apr 28, 2021, which never said Wuhan or Chinese Virus.
What exactly compelled me
to write this post is the within 100 days few acclaimed researchers jointly
addressed the media and declared the virus as "natural". It was March
of 2020, while most researchers are working on strategies to counter the
pandemic.
Updates
about Variants:
On May 4th, CCMB
study reveals N440K variant of coronavirus 10 times more infectious than others
Explaining about the high
spreading characteristics of the Covid-19 virus, Dr. Rakesh Mishra, director of
CCMB said that the ability of N440k Spike substitution mutant variant appeared
in 50% samples from south India, to generate large amounts of infectious virus
articles within a short time period are very high (10x). Dr Mishra added that the
main reason for the high rate of infections during the second wave can be
attributed to it as the variant is having an edge to produce 10 times more partials
as compared to the other mutant (B1.617 and B1.618) (Q).
The N440K variant produced ten times
higher infectious viral titers than a prevalent A2a strain, and over 1000 folds
higher titers than a much less prevalent A3i strain prototype in Caco2 cells (a
preprint of Dixit et al. 2021, Q)
Apr 20th, Feb 7th, 2021 some 13
different mutants are developed by the virus successfully.
The
B.1.617 Lineage: The variant first appeared in Oct and is now the most
common variant in India
B.1.617 carries more
then a dozen mutations but is sometimes called a “double mutant” because of two
prominent mutations: E484Q and L452R.
E484Q lies at the
same location as E484K, the “Eek” mutation that might help the
virus evades some types of antibodies.
L452R is also found
in the B.1.429 variant that is widespread in California.
Coronavirus
mutations that could 'evade immune response' flagged by Indian scientists: Report
(May 01, ‘21): There currently exists no reason to believe these mutations
could be dangerous or were expanding.
In Media
· On Mar 31st, this year,
the WHO released a joint report with Beijing on the origins of
the pandemic following a 4-week investigation in China. It concluded, among
other things, that the lab leak hypothesis was "extremely unlikely."
· "I think, there
were a lot of people who did put together the fact that you had an outbreak in
Wuhan and you have these laboratories in Wuhan fairly immediately," said
David Feith, who was an Asia adviser in the Trump administration's State Department
when the coronavirus emerged.
· Jamie Metzl, a senior fellow
at the Atlantic Council, "I'm not saying that I am certain that COVID-19
stems from an accidental lab leak, but it would be irresponsible and could only
be politically motivated to say that it's not even worth having a full
investigation".
· In Apr 2020, Foreign policy
published an article “The coronavirus is the worst intelligence failure in U.S.
history”, though it intended to defame the then-White House Administration.
· Interestingly, the same
agency in Jan 2020, had already published which thrown out of the window that
“all claims which argue, its lab-made virus are either intentional or useless”
· “How China is
Exploiting the Coronavirus to Weaken Democracies” by By Peter Rough,
in Mar 25th (a former director of research in the office of
-U.S. President George W. Bush) Beijing is using the pandemic to drive wedges
between members of the European Union and to advance its propaganda war against
the United States. As the coronavirus works its way around the globe, it is
putting unprecedented strain on public health systems and devastating economies
along its path.
· Conspiracy
theories are spreading faster than the coronavirus itself, writes on Jan 29,
2020, Justin Lig, a freelance political journalist based in Ottawa)
o On
Sun, the Washington Times - a paper with a distinct ideological bent — published an article on
Jan 26th, 2020, claiming that the virus outbreak could be linked to
a military lab in Wuhan.
o The
Wuhan Institute of Virology could have been researching military applications
for the coronavirus and may have been the source of the outbreak. The only
basis for the claim is a quote from former Israeli intelligence officer Dany
Shoham, who has expertise in biological warfare, Lig wrote in his article.
o He
further added that while Shoham never backed up the claim made in the story
that the outbreak stemmed from a biological weapon, other outlets nevertheless
picked up the idea and ran with it. Lig equipped his claim by using all means
to defame Shoham as well as everyone who supported the theory of the Wuhan
Virus. Unfortunately, Lig (doctorate in Biochemistry) failed to produce
or might not be interested in any technical fact as well, which can disprove
what Shoham has claimed.
· In a stunning revelation, a Chinese virologist, Dr Li-Meng
Yan has claimed in an exclusive conversation with 'Loose Women', a
British talk shows that the coronavirus was created in a government-controlled
laboratory in Wuhan, the original epicenter of the outbreak, and offered
scientific evidence to back her claims.
o Dr
Li-Meng, who specialized in virology and immunology at the Hong Kong School of
Public Health said that she was assigned to investigate "new
pneumonia" in Wuhan, while she discovered a cover-up operation regarding
coronavirus during her investigation.
o As
per the claim, she conducted two types of research on new pneumonia in China
first between Dec to Jan and the 2nd one in mid-Jan, before
fleeing to the US from Hong Kong.
o "There
was no response from the WHO and my supervisor. Everyone warned me that do not
cross the right line and keep silent or else I would be made to
disappear," she said.
· GreatGameIndia,
a small ‘conspiracy website’ began publishing reports last week claiming
that Canadian researchers had sold this strain of coronavirus to China.
The Toronto Sun columnist
Candice Malcolm pumped the theory on her YouTube show, asking: “Why isn’t the
mainstream media talking about the origins of this deadly virus? Could it be
linked to China’s biological warfare program?”
A group of
bioinformaticians at two universities in Delhi published a preprint scientific
manuscript on the bioRxiv preprint server on Feb 1st, 2020 has led
many to speculate wildly that 2019-nCoV may have been deliberately engineered
using HIV protein sequences.
What questions are
Ø
What is viral mutation and Why this virus
is mutating faster?
Ø
How most of the mutations are favorable to
the individual
Ø
How the mutation leads a complete copy/pest kind of sequences
Ø
Or one nucleotide which changes the entire
structure of the protein coat
Ø
Why WHO unprecedently in a faster mode,
certified that COVID-19 is the product of natural selection, while most of the
world even not reached the complete sequencing.
To understand the series of
questions, one has to understand the basics of Covid virology
Basics
of the viral genome:
The virus is enveloped, spherical, about 120 nm in diameter. The RNA genome is associated with the N protein to form the helical nucleocapsid for the genus coronavirus. Monopartite, linear ssRNA (+) genome of 27-32kb in size, the largest of all RNA virus genomes. Capped, and polyadenylated. The leader RNA (65-89 bp) at the 5' end of the genome is also present at the end of each sub-genomic RNAs. The lengths range from 27317 nucleotides for HCoV-229E to 31,357 nucleotides for the murine hepatitis virus-A59, establishing the coronavirus genome is the largest known among RNA viruses.
Most of the Mutations are reported in Spike protein, which is responsible to increase the infectivity of the virus.
The basic organization of the coronavirus genome is shared with other members of the Nidovirus order (the torovirus genus, also in the family Coronaviridae, and members of the family Arteriviridae) in that the nonstructural proteins involved in proteolytic processing, genome replication, and subgenomic mRNA synthesis (transcription) (an estimated 14-16 end products for coronaviruses) are encoded within the 5'-proximal two-thirds of the genome on gene 1 and the (mostly) structural proteins are encoded within the 3'-proximal one-third of the genome (8-9 genes for coronaviruses). Genes for the major structural proteins in all coronaviruses occur in the 5' to 3' order as S, E, M, and N. The precise strategy used by coronaviruses for genome replication is not yet known, but many features have been established (Q). The minimum sequence requirements for autonomous replication of an RNA replicon, and the importance of gene order in genome replication.
Enzymatic
activities and characteristics of coronavirus nsp protein domains (Q)
Activity | Location and designation | Architecture | Comments |
Papain-like proteinase | One or two PLpro domains within nsp3 | Finger-palm-thumb | Fingertips contain zinc-binding domain |
ADP-ribose 1"-phosphatase | ADRP (or X) domain within nsp3 | Three-layered α/β/α | Also found in other plus-strand RNA viruses |
3C-like cysteine proteinase | nsp5 (3CLpro or main protease, Mpro) | Twelve antiparallel β-strands | Extra, α-helical, carboxyl-terminal domain III |
RNA-dependent RNA polymerase | RdRp domain within nsp12 | Finger-palm-thumb (predicted) | RdRp motif VI signature GDD replaced with SDD |
5′-to-3′ helicase (associated, NTPase, and RNA 5′-triphosphatase activities) | HEL domain within nsp13 | Modeled to Escherichia coli Rep helicase | Adjacent to amino-proximal, binuclear, zinc-binding domain |
3′-to-5′ exonuclease | ExoN domain within nsp14 | Hexahelical bundle (predicted) | Unable to cleave ribose 2′-O-methylated RNA substrates |
Uridylate-specific endoribonuclease | NendoU domain within nsp15 | Wing-body-wing (butterfly fold) | Active in hexameric form; RNA bound to the internal cavity |
S-adenosylmethionine-dependent 2′-O-methyltransferase | nsp16 (MT) | Methyltransferase fold (predicted) | Activity yet to be determined |
What is viral mutation and Why this virus is mutating
faster?
Mutation is a
natural phenomenon in living organisms that cause changes in the body or
germplasm. Its chances are directly proportional to the exposure of genetic
material of the individual and since it's quite exposed in the case of Viruses,
chances are accordingly increased. Nevertheless, in most cases, the mutation is
harmful to the individual, while in this case, it seems to reverse. Beneficial
mutations occur every 7 - 10 years on average, leading to 1 - 2 generations per
year. This requires 100-200 generations per year.
Rates of
spontaneous mutation per genome as measured in the laboratory are remarkably
similar within broad groups of organisms but differ strikingly among groups.
Mutation rates in RNA viruses, whose genomes contain ca. 104 bases, are roughly
1 per genome per replication for lytic viruses and roughly 0.1 per genome per
replication for retroviruses and a retrotransposon. However, the rate of retrovirus mutation per genome per
replication in retroelements ranges from 0.04 to 0.22 Spleen necrosis virus to
HIV (Drake et. al. 1998). This is also alarming to humankind.
Even with the vaccine and
medications against this virus, future outbreaks of similar viruses and
pathogens are likely to continue. Therefore, apart from curbing this outbreak,
government policies and efforts should be made to formulate thorough measures
to prevent future outbreaks of viruses (Q).
How most of the mutations are favorable to the individual
As per new data, though
it is observed that SARS-CoV-2 binds to its receptor on the host cells with
higher affinities than SARS-CoV, the fatality rate caused by SARS-CoV-2 (3.4%)
is significantly less than the reported rate of SARS-CoV (9%–11%, WHO). The
reasons behind these differences remain elusive, and future research will shed
light on these variations. Recent sequencing data indicate that the
SARS-CoV-2 mutation rate is approximately 25 mutations per year (Mittal, et
al 2020).
The teams used
different pseudovirus systems and tested them on various kinds of cells, but
the experiments pointed to the same conclusion: viruses carrying the G mutation
infected cells much more ably than did D viruses — up to ten times more
efficiently, in some cases (Q).
In laboratory
tests, “all of us agree that D to G is making the particles more infectious”,
says Jeremy Luban, a virologist at the University of Massachusetts Medical
School in Worcester. “The bottom line is, they’re not the virus,” says Luban.
|
|
|
Note the impact of change in single
Nucleotide, A to G
|
Some labs are now working with infectious SARS-CoV-2 viruses that differ by
only a single amino acid. These are tested in laboratory cultures of human lung
and airway cells, and lab animals such as ferrets and hamsters. For labs with
the experience and the biosafety capabilities to manipulate viruses, “this is
like bread-and-butter kind of work”, says Sheahan. The first of those studies,
led by researchers at the University of Texas Medical Branch in Galveston, was
reported in a Sept 2nd preprint. It found that viruses with the
mutation were more infectious than were D viruses in a human lung cell line and
airway tissues and that mutated viruses were present at greater levels in the
upper airways of infected hamsters.
We do not find any
indication that patients infected with the Spike 614G variant have higher
COVID-19 mortality or clinical severity, but 614G is associated with higher
viral load and younger age of patients. Significant
differences in growth and size of 614G phylogenetic clusters indicate a need
for continued study of this variant (Q).
The analysis was done by
Paraskevis et al (2020), suggests that the 2019-nCoV although
closely related to BatCoV RaTG13 sequence throughout the genome (sequence
similarity 96.3%), shows discordant clustering with the Bat_SARS-like
coronavirus sequences.
Specifically, in the
5′-part spanning the first 11,498 nucleotides and the last
3′-part spanning 24,341–30,696 positions, 2019-nCoV and RaTG13 formed
a single cluster with Bat_SARS-like coronavirus sequences, whereas, in the
middle region spanning the 3′-end of ORF1a, the ORF1b, and almost half of the
spike regions, 2019-nCoV and RaTG13 grouped in a separate distant lineage
within the sarbecovirus branch.
How the
mutation leads a complete copy/pest Kind of sequences
The S protein on the
surface of the virus is a key factor involved in infection. It is a trimeric
class-I TM glycoprotein responsible for viral entry, and it is present in all
kinds of HCoVs, as well as in other viruses such as HIV (HIV glycoprotein 160,
Env), influenza virus (influenza hemagglutinin, HA), paramyxovirus
(paramyxovirus F), and Ebola (Ebola virus glycoprotein) (Q, Q). Similar to other
coronaviruses, the S protein of SARS-CoV-2 mediates receptor recognition, cell
attachment, and fusion during viral infection (Q, Q, Q, Q, Q, Q).
All coronaviruses genomes
with a variable 6-11 open reading frames (ORFs), which encode non-structural
proteins as well as structural proteins: spike glycoprotein (S), a small
envelope protein (E), matrix protein (M), and nucleocapsid protein (N).
SARS-CoV-2 is related to
SARS-CoV, the virus that causes SARS, in addition to SARS-like bat CoVs (RaTG13/CoVZC45/CoVZCX21).
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.
In one analysis, there
were 380 amino acid substitutions between SARS-CoV-2 and SARS/SARS-like viruses,
specifically located in nsp2 & nsp3. 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.
While, Laura D Manzanares-Meza, (2020) claimed that SARS-CoV-2
has a proofreading mechanism, which results in a low mutation rate compared to
influenza. E1KC4 and camostat mesylate are potential inhibitors of SARS-CoV-2 S
protein, achieving an effect similar to oseltamivir. Due to the SARS-CoV-2 low
mutation rate, nucleoside analogs have been developed (such as EIDD-2801),
which insert lethal mutations in the viral RNA (Q).
When COVID-19 spread
around the globe this year, David Montefiori wondered how the deadly
virus behind the pandemic might be changing as it passed from person to person.
Montefiori is a virologist who has spent much of his career studying how chance
mutations in HIV help it to evade the immune system–Nature (Q).
"I think the genetics will tell you about the virus. I
think it would be very difficult to tell you where it got into the human
population and how it spread and whether it came from a lab or it didn't come
from the lab. I think that's going to be very hard," said Barry
Bloom, an immunologist and infectious disease expert at Harvard T.H. Chan
School of Public Health.
We can see this occurring with the novel coronavirus right now.
It is quickly gaining mutations, called E484K and 501Y, that make it more
infectious, and doing so in independent lineages across the globe, according to
research by evolutionary microbiologist Vaughn Cooper of the University of
Pittsburgh Medical Center. This is happening naturally because millions of
infections around the globe have provided millions of opportunities for
mutations, virologist Adam Lauring of the University of Michigan told Scientific
American, published in Oped and Analysis section. It is not happening
because of a lab leak. However, no answer
available so far, "as to why only this virus of its family mutating so fast but
others couldn’t". Also, how the mutations are only increasing their virulence and infectivity?
"NOW, let's see the other side of the picture. So what more
questions should be asked? could it possible to make it in the laboratory? And the
answer is very much yes! The next question is for what? The reason is before
the world.....And the last question could be why the world is silent, and the answer
is not the world is silent but voices against the origin are made silence."
Conclusively:
What we
would or wouldn’t even know if such change (s) was (were) natural or
engineered because even if, it has (have) been engineered, the engineers are
not alive to tell us than what to say about the record!
Has Covid-19 leaked Unintentionally or Intentionally?
