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Michael Novakhov – SharedNewsLinks℠: 7:11 AM 6/28/2020 – The Barcelona COVID-19 discovery questions prevailing assumptions – Michael Novakhov – SharedNewsLinks℠: "This study suggests that the story behind COVID-19 may not be as clear or as simple as initially thought. Science must lead the way in determining its origin, which may challenge our popular assumptions and reasoning. The precise origin of COVID-19 is not scientifically certain."



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7:11 AM 6/28/2020 – The Barcelona COVID-19 discovery questions prevailing assumptions – Michael Novakhov – SharedNewsLinks℠ | InBrief | 





Michael Novakhov – SharedNewsLinks 
The Barcelona COVID-19 discovery questions prevailing assumptions – CGTN
SARS-CoV-2 has been evolving for at least 7 years
Disease X-19 News Review In Brief – 11:41 AM 6/27/2020: SARS-CoV-2 has been evolving for at least 7 years
Disease X-19 News Review In Brief – 10:58 AM 6/27/2020: » mikenov on Twitter: SARS-CoV-2 Traces Detected in Barcelona Waste Water From March 2019 | Technology Networks
9:42 AM 6/27/2020 – SARS-CoV-2 has been evolving for at least 7 years: “We used detailed phylogenetic analysis, ancestral sequence reconstruction, and molecular dynamics simulations to examine the Spike-RBDs functional evolution, finding to our surprise that it has likely possessed high affinity for human cell targets since at least 2013.”
SARS-CoV-2 has been evolving for at least 7 years
Detailed phylogenetic analysis of SARS-CoV-2 reveals latent capacity to bind human ACE2 receptor | bioRxiv
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Michael Novakhov – SharedNewsLinks 
The Barcelona COVID-19 discovery questions prevailing assumptions – CGTN
Michael_Novakhov shared this story .

Coronavirus. /VCG
Coronavirus. /VCG
Editor’s note: Tom Fowdy is a British political and international relations analyst and a graduate of Durham and Oxford universities. He writes on topics pertaining to China, the DPRK, Britain and the U.S. The article reflects the author’s opinions, and not necessarily the views of CGTN.
On Saturday, news emerged that Spanish virologists had discovered purported traces of the COVID-19 virus in samples of Barcelona wastewater that were collected in March 2019. The team at the University of Barcelona had been testing sewage since April in order to identify new potential outbreaks of the virus and subsequently found what they believe to be its genome from that a sample over a year ago.
“The levels of SARS-CoV-2 were low but were positive,” scientist Albert Bosch told the media. Although more testing is needed to ensure the result is not a false positive, the finding was nevertheless described as “suggestive” and has been submitted for peer review. 

It is too early to draw large-scale conclusions from the development, but it should nonetheless be used to question our deepest-held assumptions. We are ultimately still learning about this virus and where it came from.
Scientifically, there is no comprehensive answer concerning its development. Certain actors, however, have sought to pinpoint the virus directly to make certain cultural and political points.
This study suggests that the story behind COVID-19 may not be as clear or as simple as initially thought. Science must lead the way in determining its origin, which may challenge our popular assumptions and reasoning.
The precise origin of COVID-19 is not scientifically certain. What experts know is that the genome behind the virus is of a zoonotic origin, which at some point crossed the species barrier via an unknown intermediate host and mutated into something contagious to humans. 

However, the circumstances as to how it specifically emerged are yet to be determined and remain a mystery on a scientific and research level. While the development of a cluster of cases at the Huanan Seafood Market in Wuhan has received repeated attention as the purported point and time of origin, this is also not established scientific consensus.
Prof. Stephen Turner, head of the department of microbiology at Melbourne’s Monash University, told The Guardian back in April: “I don’t think it’s conclusive by any means,” while Donna Lu, writing in the New Scientist magazine the same month, also highlighted the mysteries regarding the certainty of its precise origin.

Medical workers pay a silent tribute to martyrs who died in the fight against the novel coronavirus disease (COVID-19) outbreak and compatriots who died of the disease, at Huoshenshan Hospital in Wuhan, central China’s Hubei Province, April 4, 2020. /Xinhua
Medical workers pay a silent tribute to martyrs who died in the fight against the novel coronavirus disease (COVID-19) outbreak and compatriots who died of the disease, at Huoshenshan Hospital in Wuhan, central China’s Hubei Province, April 4, 2020. /Xinhua
The rest of course is all political narrative, with the “China virus” line having been hammered by politicians, media outlets and other non-scientific actors who have sought to weaponize a stigmatic blame game against the country and thrive on culturalist and ideological tropes to draw pre-determined conclusions.
The public, of course, always wants immediate, simple answers and in general lacks the patience, rationality, foresight and perspective of professional scientists. As a result, the new Barcelona findings are suggestive in reminding us that the prevailing public “ideas” concerning the virus are not helpful or informative at all.
The potential presence of virus genomes existing a year previously in Spain does not of course give us new conclusions or consensus regarding the origins of COVID-19, it does not mean it “originated” there merely by having a presence, but by showing it at an earlier location, at an earlier time, serves to question the prevailing public logic across the world.
In this case, the development serves to remind the world that we cannot be armchair experts in virology and we do not know as much about the virus as we think. Because what is a very simple and straightforward word, “virus,” for the public, is in fact an extremely complex and often immeasurable subject for actual scientists.
Thus, understanding and mapping out COVID-19 is a timely process of discovery, which, owing to the mood and emotions of the public, may not always tell people the “stories” that they have assumed or even want to hear. This is why a scientific determination must come before a political one.
(If you want to contribute and have specific expertise, please contact us at opinions@cgtn.com.)
SARS-CoV-2 has been evolving for at least 7 years

Michael_Novakhov shared this story from The Medical News.

The current COVID-19 pandemic demonstrates the vast unknown of virology, which continues to challenge the ability of humanity to remain healthy when faced with pathogens. While most known microbes have restricted affinity for specific species, continuing to adapt with the host species, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has crossed over from an unknown animal reservoir, like the preceding SARS and MERS coronaviruses, to infect human cells. Such viruses are typically more readily infective and cause more severe disease, as they have not yet adapted fully to the target host.

Novel Coronavirus SARS-CoV-2 Colorized scanning electron micrograph of an apoptotic cell (green) heavily infected with SARS-COV-2 virus particles (purple), isolated from a patient sample. Image captured at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. Credit: NIAIDNovel Coronavirus SARS-CoV-2 Colorized scanning electron micrograph of an apoptotic cell (green) heavily infected with SARS-COV-2 virus particles (purple), isolated from a patient sample. Image captured at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. Credit: NIAID

Acquiring Potential for Human Infection

The burning question is how novel viruses acquire the ability to recognize, bind to and enter human cells for the first time whether this is dependent only on viral proteins recognizing host cell proteins, or adaptations in other viral processes that allow replication in a human host.
This issue is discussed by researchers at the University of Calgary in a new study published on the preprint server bioRxiv* in June 2020. The spike protein is the most well known of the SARS-CoV-2 proteins, and its binding to ACE2 receptors on the host cell is responsible for viral entry into the target cell. The human ACE2 (hACE2) has some rare variants which make the host more vulnerable to infection. Similarly, the spike protein of this virus has a greater affinity for the receptor than the previous SARS virus, which is another possible explanation for the increased infective potential of the current virus.

The Study: Origin of ACE2 Binding Affinity

The current study examines the origin of this spike protein variant with its affinity for  hACE2, using molecular dynamics (MD) simulations along with sequence reconstruction to identify the adaptation pathway of the virus. The result is a preliminary phylogenetic analysis that agrees with earlier studies the virus is 96% similar to the bat coronavirus (RaTG13) genome and 90% similar to the Pangolin-CoV genome.
The next step was to carry out a more detailed analysis of 479 sequences collected from December 30, 2019, to March 20, 2020, where they found 16 variants. Of these, 11 were missense mutations occurring in 5% or more of cases, and each had its own phylogenetic route.
The researchers then tried to recreate the ancestral sequence for the spike-RBD region, so that they could identify the important mutations that specifically drive its recent adaptation to the human host. They reconstructed the hypothetical common ancestor spike-RBD sequence for all human SARS-CoV-2 cases, called N1, and for the common ancestor with the closest animal virus, called N2.
N1 is identical to the sequence in the SARS-CoV-2 reference sequence, but the N0 sequence is unique, which shows that this virus has originated uniquely. The two differ at 4 positions. The ancestral protein gave rise to various descendants, one of which is the RaTG13. Since this was around in 2013, the researchers conclude that the ancestral strain existed as early as that year, at least. In other words, the N0-N1 branch has been evolving for at least 7 years.

Ancestral Sequence Had Higher Binding Affinity

What are the functional differences between N0 and current spike-RBD sequences? The researchers used MD simulations of the spike-RBD-hACE2 complex, beginning with the X-ray crystal structures. The model showed that the free binding energy for this complex decreased as N0 changed to N1. Thus, this actually reduced the binding affinity both in the simulations and in vitro.
However, two of the changes were associated with more significant decreases than the other. This shows that the N0 strain had, unexpectedly, greater binding affinity than the N1 strain. This is the first study to show that the common ancestor of both SARS-CoV-2 and the RaTG13 had the ability to bind to the ACE2 receptor in humans.

Other Molecular Changes Key to Infectivity

The implications are that firstly, the binding affinity of the spike-RBD to hACE2 is not the primary driver of the highly infectious nature of the current virus since the ancestral virus was capable of doing this too. Secondly, the researchers suggest that this virus was, even then, able to bind tightly to the receptor. Therefore, this was not sufficient to produce the currently observed ability to spread rapidly and widely among humans. Instead, this must be due to another set of mutations in the viral genome.
Yet another implication is that the current virus may not have jumped to humans from an animal origin at all because its affinity for hACE2 was not a recently acquired molecular trait. This may mean that the ability to infect human cells was present over a more extended period in the past, but produced less obvious or fewer clinical symptoms which passed unnoticed. Another alternative was that it affected only a small number of people, allowing it to remain under the public health radar.

Characterization of SARS-CoV-2 Spike-RBD functional evolution. A. Table of MM/PBSA binding energies between receptor binding domains of SARS-CoV2 evolutionary constructs and hACE2 receptor (note that lower energy indicates tighter binding). Blue cells indicate the presence of the ancestral (N0) state and green cells (with an x) indicate the presence of the SARS-CoV-2 state (N1) at a given position. Two values are present for constructs with an ancestral (N0) state at position 498 (which reflect the ambiguity of its ancestral reconstruction), corresponding to h498 and y498 from left to right. Energies are shown as the mean of three replicate simulations with SEM indicated in parenthesis. B. Relative effect of changes in SARS-CoV-2 receptor binding domain from ancestral (N0) to SARS-CoV-2 (N1) state on MM/PBSA binding energies. Size of spheres indicate the relative magnitude, with red spheres indicating decreased binding affinity and blue indicating increased binding affinity. Values are averaged for h498 and y498 states (both raw values shown in parentheses). C. Schematic of two possible evolutionary scenarios stemming from the observed evolutionary SARS-CoV-2 Spike-RBD function. In Scenario 1, it is postulated that a zoonotic ancestral SARS-CoV-2 strain possessed the ability to effectively bind hACE2 but was unable to effectively enter human cells, requiring the presence of subsequent mutations to infect humans. In Scenario 2, an ancestral SARS-CoV-2 strain was actively infecting humans prior to the outbreak at low levels, thus escaping public health detection until subsequent mutations lead to increased infectivity and/or severity.Characterization of SARS-CoV-2 Spike-RBD functional evolution. A. Table of MM/PBSA binding energies between receptor binding domains of SARS-CoV2 evolutionary constructs and hACE2 receptor (note that lower energy indicates tighter binding). Blue cells indicate the presence of the ancestral (N0) state and green cells (with an x) indicate the presence of the SARS-CoV-2 state (N1) at a given position. Two values are present for constructs with an ancestral (N0) state at position 498 (which reflect the ambiguity of its ancestral reconstruction), corresponding to h498 and y498 from left to right. Energies are shown as the mean of three replicate simulations with SEM indicated in parenthesis. B. The relative effect of changes in the SARS-CoV-2 receptor-binding domain from ancestral (N0) to SARS-CoV-2 (N1) state on MM/PBSA binding energies. Size of spheres indicates the relative magnitude, with red spheres indicating decreased binding affinity and blue indicating increased binding affinity. Values are averaged for h498 and y498 states (both raw values shown in parentheses). C. Schematic of two possible evolutionary scenarios stemming from the observed evolutionary SARS-CoV-2 Spike-RBD function. In Scenario 1, it is postulated that a zoonotic ancestral SARS-CoV-2 strain possessed the ability to effectively bind hACE2 but was unable to effectively enter human cells, requiring the presence of subsequent mutations to infect humans. In Scenario 2, an ancestral SARS-CoV-2 strain was actively infecting humans prior to the outbreak at low levels, thus escaping public health detection until subsequent mutations lead to increased infectivity and/or severity.

Future Research

These possibilities can only be tested by a broad-spectrum approach to sequencing all coronavirus strains in human populations, as this will reveal the presence of closely related viruses if such are present.
The current study is an in silico study, and further validation of these findings is necessary using combinatorial libraries which can be screened to map functionalities to the genomic regions of the virus. This will help understand how the virus evolved in the most recent past.
The researchers conclude: It appears that the SARS-CoV-2 Spike-RBD did not recently evolve binding affinity to a human-specific protein. Instead, that function appears to have been latent, making it clear that the evolution of this disease along with so many other aspects of its etiology is more complex than expected.

*Important Notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Disease X-19 News Review In Brief – 11:41 AM 6/27/2020: SARS-CoV-2 has been evolving for at least 7 years

Michael_Novakhov shared this story from Covid-19-Review.

Disease X-19 News Review In Brief – 11:41 AM 6/27/2020
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Michael_Novakhov shared this story from Covid-19-Review.

Is COVID-19 the dreaded 'Disease X' scientists warned us about?

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10:58 AM 6/27/2020 

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