1:38 PM 7/29/2020 - Researchers identify evolutionary origins of SARS-CoV-2
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| 8:27 AM 7/28/2020 – I think, that the investigation into the origins of the Disease -X-19 (“Covid-19”) has to be structured as the counterintelligence – criminal one, and to include the epidemiological and other data. Good DETECTIVES are needed! | New Abwehr – KGB – Russian Mob Incite the R-R-Revolution in AmeriKa! | 2:32 PM 7/26/2020 – American protests: Demonstrations, violent riots expected to continue throughout the country | ||
8:27 AM 7/28/2020
I think, that the investigation into the origins of the Disease -X-19 (“Covid-19”) has to be structured as the counterintelligence – criminal one, and to include the epidemiological and other data. Good DETECTIVES are needed! – M.N. | 8:32 AM 7/27/2020
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Covid-19-Review.To #US & #Senate:
Present #Covid19 #Crisis is direct result of gross #incompetence & #stupidity of #FBI & #CIA. Both could be #penetrated and #subverted. New centralized structure after 9/11 was not a #solution. #INVESTIGATE & #REPLACE them, #ASAP or you will lose this #country!
New Abwehr – KGB – Russian Mob Incite the R-R-Revolution in AmeriKa!
The KGB und Friends intend to start a “Revolution in AmeriKa” or at least to put up a nice show, all according to their well thought out plans for “Covid world”. What are the FBI-CIA plans? Do they have any?
1:40 PM 7/18/20201:40 PM 7/18/2020 – Covid-19 as the political, information, and the biological weapon of the New Abwehr and their tool, Russian-Jewish Mafia or TOC – GSSaved, Shared Stories, Tweets – on RSS Dog In 250 Posts | Page | In Brief – Page |
I respectfully recommend to WHO and the Scientific Community to rename “Covid-19” into the “Disease X-19”, because the etiology of this syndrome is highly uncertain, and it might involve more pathogens than Sars-Cov-2 alone (possibly Hantaviruses, ASF, and/or other infections). Furthermore; presently, as reported by the clinicians, the clinical picture appears to be the complex multi-organ – multi-system failures, it looks quite different from the one which was initially observed and described in China in the beginning of 2020. It is more than just the terminology; it is the correct unbiased thinking and the correct, fruitful research and the interventions. Naturally, the broader outlook changes the perspectives on the evaluation: all the relevant lab tests have to be performed, including on the old preserved samples. The comprehensive studies, testing this hypothesis are needed. It looks like from the times of Antiquity the Co-infections were the preferred tool of the Biowarfare as the simple method of increasing the pathogenic efficiency. The unusual and well documented proliferation of rodents, including the large rats in the major cities globally, along with their noticeably abnormal behavior is a clue that they might be the vectors in the transmissions of the combined infections. The recent, in the last several years, mostly reported in 2013-1019 massive epizootics of the viral illnesses in pigs livestock in China are the reasons for concern as the possible source of the infections in rodents and the possible zoonotic jump in the present Pandemic. This line of thought corresponds with the recently reported data about the earlier than thought previously emergence of the Pandemic: in the Spring-Summer of 2019, both in China and Europe, and the theoretical (computational) possibility of the Sars-Cov-2 emergence since at least 2013. We have to understand the nature of the Disease X-19, before we attempt to determine its origins. Michael Novakhov | 7.13.20
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| Researchers identify evolutionary origins of SARS-CoV-2 | ||||
By reconstructing the evolutionary history of SARS-CoV-2, the virus that is responsible for the COVID-19 pandemic, an international research team of Chinese, European and U.S. scientists has discovered that the lineage that gave rise to the virus has been circulating in bats for decades and likely includes other viruses with the ability to infect humans. The findings have implications for the prevention of future pandemics stemming from this lineage.
Coronaviruses have genetic material that is highly recombinant, meaning different regions of the viruss genome can be derived from multiple sources, said Maciej Boni, associate professor of biology, Penn State. This has made it difficult to reconstruct SARS-CoV-2s origins. You have to identify all the regions that have been recombining and trace their histories. To do that, we put together a diverse team with expertise in recombination, phylogenetic dating, virus sampling, and molecular and viral evolution.
The team used three different bioinformatic approaches to identify and remove the recombinant regions within the SARS-CoV-2 genome. Next, they reconstructed phylogenetic histories for the non-recombinant regions and compared them to each other to see which specific viruses have been involved in recombination events in the past. They were able to reconstruct the evolutionary relationships between SARS-CoV-2 and its closest known bat and pangolin viruses. Their findings appear today (July 28) in Nature Microbiology.
The researchers found that the lineage of viruses to which SARS-CoV-2 belongs diverged from other bat viruses about 40-70 years ago. Importantly, although SARS-CoV-2 is genetically similar (about 96%) to the RaTG13 coronavirus, which was sampled from a Rhinolophus affinis horseshoe bat in 2013 in Yunnan province, China, the team found that it diverged from RaTG13 a relatively long time ago, in 1969.
The ability to estimate divergence times after disentangling recombination histories, which is something we developed in this collaboration, may lead to insights into the origins of many different viral pathogens, said Philippe Lemey, principal investigator in the Department of Evolutionary and Computational Virology, KE Leuven.
The team found that one of the older traits that SARS-CoV-2 shares with its relatives is the receptor-binding domain (RBD) located on the Spike protein, which enables the virus to recognize and bind to receptors on the surfaces of human cells.
This means that other viruses that are capable of infecting humans are circulating in horseshoe bats in China, said David L. Robertson, professor of computational virology, MRC-University of Glasgow Centre for Virus Research.
Will these viruses be capable of jumping directly from bats into humans or will an intermediate species be required to make the leap? According to Robertson, for SARS-CoV-2, other research groups incorrectly proposed that key evolutionary changes occurred in pangolins.
SARS-CoV-2s RBD sequence has so far only been found in a few pangolin viruses, said Robertson. Furthermore, the other key feature thought to be instrumental to SARS-CoV-2s ability to infect humans a polybasic cleavage site insertion in the Spike protein has not yet been seen in another close bat relative of the SARS-CoV-2 virus. Yet, while it is possible that pangolins may have acted as an intermediate host facilitating transmission of SARS-CoV-2 to humans, no evidence exists to suggest that pangolin infection is a requirement for bat viruses to cross into humans. Instead, our research suggests that SARS-CoV-2 likely evolved the ability to replicate in the upper respiratory tract of both humans and pangolins.
The team concluded that preventing future pandemics will require better sampling within wild bats and the implementation of human disease surveillance systems that are able to identify novel pathogens in humans and respond in real time.
The key to successful surveillance, said Robertson, is knowing which viruses to look for and prioritizing those that can readily infect humans. We should have been better prepared for a second SARS virus.
Boni added, We were too late in responding to the initial SARS-CoV-2 outbreak, but this will not be our last coronavirus pandemic. A much more comprehensive and real-time surveillance system needs to be put in place to catch viruses like this when case numbers are still in the double digits.
Other authors on the paper include: Xiaowei Jiang, lecturer in bioinformatics, Xian Jiaotong-Liverpool University; Tommy Tsan-Yuk Lam, assistant professor of public health, University of Hong Kong; Blair Perry, graduate student, University of Texas Arlington; Todd Castoe, associate professor of biology, University of Texas Arlington; and Andrew Rambaut, professor of molecular evolution, Institute of Evolutionary Biology, University of Edinburgh.
Support for this research was provided by the European Research Council, the Medical Research Council, the Research Foundation Flanders and the National Natural Science Foundation of China.
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| 10:44 AM 7/29/2020 - Is this the sign of the "rational" (lab, man-made) rather than the "natural" design of this infection(s) and its pathogen(s)? | ||||
 10:44 AM 7/29/2020 Is this the sign of the "rational" (lab, man-made) rather than the "natural" design of this infection(s) and its pathogen(s)? "the increased infectivity of the G-form is likely due to a higher rate of profitable binding encounters with the host receptor." - The SARS-CoV-2 Spike Variant D614G Favors an Open Conformational State
Saved and Shared Stories from Michael_Novakhov | Page Headlines | Saved and Shared Stories In 250 Brief Posts ___________________________________________________________________ Michael Novakhov - SharedNewsLinks - Latest Post | ||||
| Emergent SARS-CoV-2 D614G spike mutation more infective due to "open" morphology | ||||
Researchers from the Los Alamos National Laboratory and Duke Human Vaccine Institute & Department of Surgery demonstrated that globally prevalent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with the amino acid substitution D614G in the spike protein is much more infective due to profitable binding encounters with the host receptors. Their findings are currently available on the bioRxiv* preprint server.
Coronavirus disease (COVID-19) caused by SARS-CoV-2 represents a salient global health emergency. This virus infects human cells by utilizing the receptor-binding domain (RBD) of the trimeric spike protein to bind to the angiotensin-converting enzyme 2 (ACE2) receptor found in many cells of the human body.
Amidst the COVID-19 pandemic, the emergence of a SARS-CoV-2 variant, which carried the amino acid substitution D614G in the spike protein, has been observed. Very soon, that exact viral strain became globally prevalent.
Mechanistically speaking, in the "all-down" spike conformation, all three RBDs of the protomers are in the closed orientation. However, binding of the RBD to ACE2 necessitates the transition of one of the protomers from the closed to an open conformation.
Such an infection-capable configuration is referred to as open or "one-up" spike conformation. Consequently, the resulting G-form is considered more infectious in the laboratory conditions and associated with increased viral loads in infected people.
To identify the factors that lead to such distinct viral dynamics, a research group from the Los Alamos National Laboratory and Duke Human Vaccine Institute & Department of Surgery in the United States conducted a meticulous mechanistic analysis and obtained some interesting and novel insights.
Structural Representation of the Spike protein. (A) The Spike complex is shown in the all-down conformation. Its S1 and S2 subunits are depicted in red and blue. (B) The Spike complex is shown in the one-up conformation. It is composed of three protomers, with the L-down protomer depicted in purple, the Up protomer in orange, and the R-down protomer in cyan. The dashed white circle indicates a D614G site. Here, only one of the three D614G sites are shown. (C) Definition of twelve domains and their residues used for analysis of simulations. It was necessary to define domains for every region for analysis, so some regions may have arbitrarily assigned names or not follow canonical sequence ranges. We display the domains highlighted in the Spike structure, shown from two different perspectives. Definitions of domain abbreviations: NTD, N-Terminal Domain; CT0, C313 Terminal domain 0; RBD, Receptor Binding Domain; CT1, C-Terminal domain 1; CT2, C-Terminal domain 2; S2S2, S1/S2 Cleavage to S2; FP, Fusion Peptide; FPR, Fusion Peptide Region; HR1, Heptad Repeat 1; CH, Center Helix; CD, Connector Domain; and CD1, Connector Domain 1. Images in (A)-(B) were created with PyMol (15); images in (C) were prepared using VMD (16).
Appraising molecular-level impacts
In a nutshell, this study successfully used multifarious replicas of microsecond all-atom simulations in order to probe the molecular-level impact of the amino acid substitution D614G on closed and open states of the SARS-CoV-2 spike protein.
Hydrogen bonding interactions of the speculated critical residues were studied in-depth, primarily to observe whether hydrogen bond reduction can lead to a conformational relaxation of the spike protein.
Moreover, a global differential contact analysis was also pursued, and the researchers have modeled the impact of highly-flexible glycan ensembles on RBD exposure and epitope shielding with the use of a quantitative measure known as the glycan encounter factor.
A higher rate of profitable binding encounters
More specifically, the G614 form was shown to lead to a rearrangement in residue-residue contacts and hydrogen bonding that would lead to an increased population of the one-up spike ensemble or open conformations.
Likewise, a careful analysis of RBD exposure (including the role of highly-flexible glycans) revealed that both the ACE2 binding site and critical neutralizing antibody epitopes in the RBD are definitely more accessible in the one upstate.
As a consequence, the increased infectivity of the aforementioned G-form can be observed, likely arising due to a much higher rate of profitable binding encounters with the receptor located at the host cells.
RBD is significantly more exposed in the one-up conformation. (A) Surface representation of the all-down Spike complex. Colors ranging between red, white and blue represent values for the glycan encounter factor (GEF). GEF describes relative exposure and coverage of protein surfaces. (B) Surface representation of the one-up Spike. Colors ranging between cyan, white, and magenta indicate GEF differences between the closed and open structures. The RBD in the up orientation is indicated by the dotted circle, where the originally buried (magenta) region around 458-478 is now exposed. (C-D) Top view of the Spike protein apex in (C) all-down and (D) one-up conformations. Protein surface is shown in grey. Glycan ensembles covering the protein surface are represented by point densities. Fucosylated 2 and 3 antennae complex (FA2 and FA3) glycans and oligomannose (OM) glycans are depicted in dark maroon, orange, and green. Binding site region, which includes receptor binding motif (residues 438-506) and C105 antibody binding residues (i.e. 403, 405, 406, 408, 409, 415-417, 420, 421, 449, 453, 455-460, 473-477, 486, 487, 489, 493-496, 498, 500-505), is colored yellow. These binding site residues are significantly more exposed in the one-up conformation, compared to the all-down case. (E) Residue-wise GEF of the RBD domain. Buried residues are colored blue. Exposure increases as the color changes toward white and red.
Change towards a higher one-up state population
This means that both ACE2 binding and RBD-targeting antibody binding are expected to increase in the one-up state; hence, a change towards a higher one-up state population probably represents a dominant effect of the D614G substitution.
Accordingly, such form is also predicted to be much more sensitive to neutralization due to enhanced exposure of the RBD, which is a primary target region for neutralizing antibodies.
In any case, the structural data and mechanistic studies presented here, the enhanced neutralizing antibody sensitivity, as well as the experimentally determined increase in infectivity make a rather consistent story with possible therapeutic implications.
*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.
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| The SARS-CoV-2 Spike Variant D614G Favors an Open Conformational State | bioRxiv | ||||
Summary
The COVID-19 pandemic underwent a rapid transition with the emergence of a SARS-CoV-2 variant that carried the amino acid substitution D614G in the Spike protein that became globally prevalent. The G-form is both more infectious in vitro and associated with increased viral loads in infected people. To gain insight into the mechanism underlying these distinctive characteristics, we employed multiple replicas of microsecond all-atom simulations to probe the molecular-level impact of this substitution on Spikes closed and open states. The open state enables Spike interactions with its human cellular receptor, ACE2. Here we show that changes in the inter-protomer energetics due to the D614G substitution favor a higher population of infection-capable (open) states. The inter-protomer interactions between S1 and S2 subunits in the open state of the D-form are asymmetric. This asymmetry is resolved in the G-form due to the release of tensile hydrogen bonds resulting in an increased population of open conformations. Thus, the increased infectivity of the G-form is likely due to a higher rate of profitable binding encounters with the host receptor. It is also predicted to be more neutralization sensitive due to enhanced exposure of the receptor binding domain, a key target region for neutralizing antibodies.
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| Two new studies suggest 'the plot thickening' | ||||
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| Covid-19 and the heart: two new studies offer insights - CNN | ||||
Covid-19's impact on the heart: Two new studies suggest 'the plot thickening' | ||||
| Russian Intelligence Agencies Push Disinformation on Coronavirus Pandemic | ||||
After the publication of this article, OneWorld.Press issued a statement saying any accusation that it worked for Russian intelligence was categorically false. To the best of our knowledge, its contributors have not been charged with crimes for cooperating with any foreign intelligence agency, the statement said.
Without evidence, OneWorld.Press claimed that the accusations about Russian intelligences propaganda efforts were being spread by officials who aimed to hurt President Trumps re-election chances. Everybody across the world knows that some members of the deep state have their daggers out for Trump, and the president himself has even said as much on countless occasions, it said.
American intelligence officials said the G.R.U.s psychological warfare unit, known as Unit 54777 or the 72nd Special Service Center, was behind the propaganda campaigns that were often devised to obscure Moscows role in creating them. A 2018 report in The Washington Post linked InfoRos to the G.R.U.s Unit 54777.
United States intelligence reports have identified two Russians, Denis V. Tyurin and Aleksandr G. Starunskiy, with ties to the G.R.U. and who make sure the messaging and disinformation drafted by the intelligence officials are pushed by InfoRos and on <a href="http://InfoBrics.org" rel="nofollow">InfoBrics.org</a> and OneWorld.Press.
Russian officials did not immediately return a request for comment.
Mr. Tyurin and Mr. Starunskiy, the American officials said, were in essence involved in a kind of information laundering, akin to money laundering. They take the messages from Russian intelligence and spread them on InfoRos, OnePress or another website.
The material created by the G.R.U. is then picked up by other websites that further spread it. Those websites are often on the fringes of the web, while some, like Global Research, have a significant following, American officials said.
The stories pushed by Russian intelligence appear to be written by native English speakers and do not stand out as products of a foreign influence campaign, American officials said.
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| Dynamic Changes of Antibodies to SARS-CoV-2 in COVID-19 Patients at Early Stage of Outbreak - Docwire News | ||||
This article was originally published here
Virol Sin. 2020 Jul 27. doi: 10.1007/s12250-020-00268-5. Online ahead of print.
ABSTRACT
The coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has spread around the world with high mortality. To diagnose promptly and accurately is the vital step to effectively control its pandemic. Dynamic characteristics of SARS-CoV-2-specific antibodies which are important for diagnosis of infection have not been fully demonstrated. In this retrospective, single-center, observational study, we enrolled the initial 131 confirmed cases of COVID-19 at Jin-Yin-Tan Hospital who had at least one-time antibody tested during their hospitalization. The dynamic changes of IgM and IgG antibodies to SARS-CoV-2 nucleocapsid protein in 226 serum samples were detected by ELISA. The sensitivities of IgM and IgG ELISA detection were analyzed. Result showed that the sensitivity of the IgG ELISA detection (92.5%) was significantly higher than that of the IgM (70.8%) (P < 0.001). The meantimes of seroconversion for IgM and IgG were 6 days and 3 days, respectively. The IgM and IgG antibody levels peaked at around 18 days and 23 days, and then IgM fell to below the baseline level at about day 36, whereas IgG maintained at a relatively high level. In conclusion, antibodies should be detected to aid in diagnosis of COVID-19 infection. IgG could be a sensitive indicator for retrospective diagnosis and contact tracing, while IgM could be an indicator of early infection.
PMID:32720214 | DOI:10.1007/s12250-020-00268-5
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| 9:22 AM 7/29/2020 - Russia spreads disinformation and incites the racial wars in America - their old trick | Russian intelligence spreading virus disinformation 29/07/20 08:40 from Saved Stories from Michael_Novakhov | ||||
 Russia spreads disinformation and incites the racial wars in America - their old trick - GS __________________________________________________________________________ 9:22 AM 7/29/2020 - Russian intelligence spreading virus disinformation 29/07/20 08:40 from Saved Stories from Michael_Novakhov 
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29/07/20 08:20 from Saved Stories from Michael_Novakhov (1 sites) In a video posted Monday online, a group of people calling themselves ... coronavirus treatment and that masks did not slow the spread of the virus. ... At least one version of the video, viewed by The Times on Facebook, was ... Clockwis... | ||||
| Russia spreads disinformation and incites the racial wars in America - their old trick - Google Search | ||||
Search ResultsWeb resultsHow Russia Tried to Start a Race War in the United States
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This. Article examines Russia's actions and considers whether they violate the international prohibitions against racial discrimination and hate speech. Table of
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| US officials say Russian intelligence spreading virus disinformation | ||||
WASHINGTON (AP) Russian intelligence operatives are using a trio of English-language websites to spread disinformation about the coronavirus pandemic, seeking to exploit a crisis that America is struggling to contain ahead of the presidential election in November, U.S. officials said Tuesday.
Two Russians who have held senior roles in Moscows military intelligence service known as the GRU have been identified as responsible for a disinformation effort directed at American and Western audiences, U.S. government officials said. They spoke to The Associated Press on condition of anonymity because they were not authorized to speak publicly.
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