If you are anything like me, you’re just as bewildered that “nobody I know” has a clue what went into their bodies with mRNA vaccines. For these mRNA vaccines to have become suddenly “safe and effective for everything”, there had to be uses elsewhere, redeployed for SARS-CoV-2. Thus, some comprehendable articles started popping up during searches. Perhaps you’ll learn as much as I. Helpful hint: Bell’s Palsey is an early symptom of AIDS. If you are unaware of recent medical revelations concerning unvaccinated death-rates, you may find this video by John Campbell of interest (see below). It appears as though the vaccine manufacturers had different “blends of vaccine” for different countries; which is reflected in the non-vaccinated death rates in comparison to others.
If you are anything like me, you are equally bewildered that CIA bribed its own analysts to avoid a bioweapon lab-leak conclusion; this is too obvious – I propose this is part of the CIA/LDS/Russian psyop to hang blame on China “solely”; to stimulate discussion of war against “a known aggressor who attempted mass-murder”. In fact, the Wuhan Lab, Saudi Arabia Lab, Nigeria Lab, South Africa Lab, French Lab, Zaporiszhie Lab in Ukraine, Winnipeg Lab, India Lab and Lugar Lab, were funded by US Army DTRA and Anthony Fauci’s CDC, NIH and NIAIH; All of those labs had a role with full knowledge of the Presidents of those countries. Comingling military, public and private research…weaponizing everything. The CCP were simply bulk-manufacturers and “bottlers” – the real origins of the virus and the chimeric creations therefrom, are firmly in Wuhan, China/Chapel Hill, North Carolina/Winnipeg, Manitoba, Canada…but release was conducted by CDC/NIH personnel under plans formulated by WHO and those who fund WHO….in collusion with Russian FSB.
Follow this link to a discussion of how the pandemic was planned -> https://qr.ae/prYQrz
This link takes you to a discussion of the origins of SARS-CoV-2 -> https://qr.ae/prUgWf
Readers may not be aware that the Pfizer vaccine which was test-trialed on 250 people was manufactured in a way that was different than the one you all received – Pfizer’s product offering to consumers is different than that which was trialed on 250 people; Pfizer vaccines are assembled in two very different manufacturing processes. In other words, the vaccines tested by Pfizer (before emergency-use-authorizarion, were different from the E-Coli-based manufacturing process used to create the mRNA vaccines in bulk. John Campbell does a superb job of exposing this.
https://www.bmj.com/content/378/bmj.o1731/rr-2
Here are links to posts on the Pfizer clinical trial – from John Campbell’s video partner. A fundamental change in process for a biologic was ushered from trial to emergency product without 1) any apparent plan to review for bioequivalence, or 2) any indication whatsoever to the public of thisdiscrepancy. That change seems relevant to informed consent, and to a physician’s ability to obtain informed consent…the *process* IS the vaccine…changing processes creates something *different.*.
https://researchrebel.substack.com/p/…
https://researchrebel.substack.com/p/…
https://researchrebel.substack.com/p/…
https://www.bmj.com/content/378/bmj.o…
https://www.nejm.org/doi/suppl/10.105…
https://twitter.com/joshg99/status/16…
https://phmpt.org/wp-content/uploads/…
Nucleoside-modified mRNAs formulated in lipid nanoparticles (mRNA-LNP) have proved to be a potent mode of immunization against infectious diseases in preclinical studies, and are being tested for SARS-CoV-2 in humans. A critical question, yet to be answered, is how mRNA-LNP vaccine immunogenicity compares to that of traditional adjuvanted protein vaccines in primates. mRNA-LNP immunization compared to protein immunization elicits either the same or superior magnitude and breadth of HIV-1 Env-specific polyfunctional antibodies. Immunization with mRNA-LNP encoding Zika premembrane and envelope or HIV-1 env gp160 induces durable neutralizing antibodies for at least 41 weeks. Doses of mRNA-LNP as low as 5 μg are immunogenic in macaques
Thus, mRNA-LNP can be used to rapidly generate single or multi-component vaccines, such as sequential vaccines needed to protect against HIV-1 infection. Human immunodeficiency virus type 1 (HIV-1) is completely dependent upon the HIV-1 env protein to enter cells. The virus typically replicates in activated CD4+ T cells due to viral entry requirements for the CCR5 coreceptor and for high surface levels of the CD4 receptor. This is the case for the transmitted virus and for most of the virus sampled in the blood. Over the course of infection, the HIV-1 env gene can evolve to encode a protein with altered receptor and coreceptor usage allowing the virus to enter alternative host cells. In about 50% of HIV-1 infections, the viral population undergoes coreceptor switching, usually late in disease, allowing the virus to use CXCR4 to enter a different subset of CD4+ T cells.
Neurocognitive disorders occur in about 10% of HIV-1 infections, also usually late in disease, but caused (ultimately) by viral replication in the brain either in CD4+ T cells or macrophage and/or microglia. Expanded host range is significantly intertwined with pathogenesis. Identification and characterization of such HIV-1 variants may be useful for early detection which would allow intervention to reduce viral pathogenesis in these alternative cell types.
Wuhan Institue of Virology deception
Have you ever heard of the Wuhan Institute of Virology’s proprietary alpha-coronavirus called WIV1-CoV? The identification of WIV1-CoV and its capacity to use ACE2 orthologs [Here, orthologs are defined as homologs in different species that catalyze the same reaction, and paralogs are defined as homologs in the same species that do not catalyze the same reaction]. This was a 2016 warning for possible “reemergence” and provided an opportunity to prepare for a future CoV outbreak. To achieve this goal, a new platform is required to translate metagenomics findings; the approach must generate critical diagnostic reagents, define emergence potential of novel strains, and determine efficacy of current therapeutics. Building on this premise, a framework to examine circulating CoVs using reverse genetic systems to construct full-length and chimeric viruses.
WIV1-CoV virus “readily and efficiently replicated in cultured human airway tissues.” The virus produces flu-like symptoms initially, and then can cause pneumonia, and compromise the body’s immune system.
The results indicate that viruses using WIV1-CoV spike were poised, in 2016, to emerge in human populations due to efficient replication in primary human airway epithelial cell cultures. However, additional adaptation, potentially independent of the spike protein receptor-binding domain, is required for pathogenesis and epidemic disease. Most compelling, however, was the discovery that monoclonal antibody strategies against SARS were effective against WIV1-CoV spike unlike available vaccine approaches- suggesting WIV1-CoV was ‘designed’ to respond to Remdesivir from Gilead Pharmaceuticals. Together, the results highlight the utility of developing platforms to evaluate circulating zoonotic viruses as threats for future emergence and epidemic potential.
Leaks of dangerous pathogens from laboratories is not a rare event and occurrences have been documented in several countries. The most notable lab leak known is the 1977 H1N1 lab escape from China that caused a worldwide pandemic.[ 61 ] The most recent one is the November 2019 outbreak of brucellosis that occurred in two research centers in Lanzhou, China, infecting over 100 students and staff members.[ 62 ] Several lab escapes of the first SARS virus have been reported as well: in the summer of 2003 in Singapore,[ 63 ] then in December 2003 in Taiwan,xviii and in the spring of 2004 twice in China.xix
Concerns about WIV’s lab safety were raised in 2018 by U.S. Embassy officials after visiting the Institute and having an interview with Zhengli Shi. The lab auditors summarized their worries in subsequent diplomatic cables to Washington.xx Chinese experts also raised concerns about lab safety in their own country, lamenting that “lab trash can contain man‐made viruses, bacteria or microbes” and that “some researchers discharge laboratory materials into the sewer after experiments without a specific biological disposal mechanism.”xxi
American labs have also had their share of safety issues. Recently, research operations in the Biosafety level (BSL)‐4 United States Army Medical Research Institute of Infectious Diseases (USAMRIID) facility in Fort Detrick were interrupted in August 2019 following safety violations, in particular, relating to the disposal of infective materials.xxii Other US labs have been cited for safety issues as well. 22 ]. https://www.pnas.org/doi/10.1073/pnas.1517719113
Saudi Arabia + co-conspirators
Roughly 13 years ago, SARS-CoV-1 was modified into a super-virulent bioweapon with a 69% death rate after 18 days of illness. This new SARS variant was named “Middle East Respiratory Syndrome” (MERS) with a cockamamy cover-story about it being a “novel” zoonotic virus from camels. This was a false story to cover-up Saudi Arabian complicity in manufacturing bioweapons…it also underscored the avarice of Saudi Arabia when it came to licensing the vaccines for 3rd-party use and tests.
MERS-CoV = SARS-CoV-1 with a CRISPR-modified ACE2 spike-gene.
Readers of this post may not be aware that Saudi Arabia complained that a patent taken out by Dutch scientists (who isolated the Middle Eastern Respiratory Syndrome (MERS) virus) was impeding Saudi efforts to track the virus within its own borders. In other words, it appears Saudi Arabia helped assemble MERS with Russian assistance, then, the CIA got involved and scooped the DNA and RNA for patent – first…irritating the Saudi Government and its partners who were left empty-handed (Germany, France, Brazil, Spain, Netherlands, China, India and Russia, to name a few).
The full extent of plans, of countries building illicit bioweapons, to use them against USA was driven home in 2019. The primary aerosolization points of the “doomsday virus” was Los Angeles, Milan, Italy and Wuhan (same locations as SARS-CoV2) – all of the co-conspirators had a hand in deciding whom they were going to kill, and whom would be left alive; the L.A. dispersal point was located in the abandoned Guatemala Trade Bureau on Willshire Blvd. Milan was chosen because over 100,000 Chinese workers were inside Milan running the clothing factories; Wuhan was chosen because of the US/China Military Olympic competitions being held in wuhan. US soldiers were a vector for disease spread. In my opinion, CIA used these locations because of the chinese presence. Why? “Plausible Deniability”.
When I traveled through Atlanta Hartsfield Airport, in February 2021, it appeared as though the airports were a vector, not a bunch of servicemen in Wuhan.. The virus spread too quickly to have such obscure origins.
In order to destroy Stalinist Communism in China, and Italy (to replace Stalinist with Trotskyite Communists, destroying the Stalinist CCP is paramount. In this fashion, CIA plans to destroy CCP are admirable, but, the downside is a more virulent form of societal control more akin to German National Socialism (NAZIs).
Gain-of-function sociopathy (MERS)
Under cover of “scheduled” military training exercises at Long Beach, 40 miles away, in downtown LA, two blackhawk helicopters, with specially-trained, hand-picked operators, landed on Willshire boulevard (near Korea Town) amidst very tall buildings to extract the deadly payload. It was “planned to be a mystery” as to origin – the Guatemala trade bureau was slated for demolition which would have aerosolized the deadly bioweapon…but it was intended to kill people within 3 weeks of infection. See YouTube video immediately below:
“World Health Organization director-general Margaret Chan in response. “No IP will stand in the way of public health”, suggesting patent theft was in her control regardless of prevailing laws. Dutch researchers, based at Erasmus Medical Center in Rotterdam, the Netherlands, say the patent does nothing to stop the Saudis developing their own tests for the coronavirus that causes MERS. The Dutch have themselves developed and published tests for both the virus and antibodies to it, essential for tracking its spread. And they say they have sent the virus to 40 labs, some of which are developing their own tests, and that they are willing to send the virus to any laboratories who can handle it safely. There have been 44 known cases of MERS worldwide, with more than 20 deaths. The Dutch team says it has repeatedly offered tests for MERS to the Saudis. Ab Osterhaus, head of the virology department at Erasmus, says the Saudis have not replied”.
Why did Saudi Arabian researchers become inflamed? Money. Dr Robert Gallo, with his dubious discovery of the caise of AIDS, demonstrated that the tests are a highly profitable means of remaining a Govt-funded researcher, while profitting in public and private companies. Gallo’s royalty-profits from his test are the envy of every researcher around the globe seeking to re-create Gallo’s success.
Ziad Memish, the deputy Saudi health minister, said that the country has been struggling to develop diagnostics because the virus has been patented. Reuters quoted Ziad Memish as saying: “
- The virus was sent out of the country [Netherlands] and it was patented, contracts were signed with vaccine companies and antiviral drug companies, and that’s why they have a Material Transfer Agreement… and that should not happen.” A Material Transfer Agreement specifies what providers and recipients of biological material can and cannot do with it.
This gain-of-function research applied to Coronavirus research represents a “gain-of-function” weaponization inserted into original SARS-CoV-1. This “escaped pathogen” was isolated from a Saudi Arabian patient with severe acute respiratory syndrome in June 2012 and the virus was later named ‘Middle East Respiratory Syndrome’ – Coronavirus (MERS-CoV) [1]. Since then, multiple outbreaks (leaks) have been reported in or been epidemiologically linked to the Arabian Peninsula Afghanistan and Pakistan. Up to April 18, 2016, the Saudi authorities reported a total of 1386 cases of which 587 died [2]. With a high mortality rate, lack of antiviral treatment, or preventive vaccine, MERS-CoV remains a major public concern. The virulence of the original MERS-CoV has been doubled from 34.5% to 69% since original tests were performed. In the event you were unaware, please see an excerpt from the Obama Whitehouse Archives proving that Obama funded gain-of-function research on pandemic pathogens 24 hours before Trump was inaugurated as POTUS.
How did this happen? Co-mingling private, public and military research as if it was a legal game of 3-card monty. It is obvious to the casual observer what has transpired – copying the Russian strategy of co-mingling private, public, and military research, we have attained another state of ‘mutually-shared destruction’; perhaps extinction. CIA started building labs all over the planet. This attracted the worst ghouls.
Ziad Memish, deputy Saudi minister for public health and head of the WHO Collaborating Centre for Mass Gathering Medicine in Riyadh, helped start an international collaboration to study health at the Hajj, and wrote recently that “sharing of information and research findings are critically important elements of the programme”. It turns out, Ali Zaki, a virologist at the Dr. Soliman Fakeeh Hospital in Jeddah, the first to identify dengue fever and a new tick-borne flavivirus in Saudi Arabia. It was Zaki who sent samples from a mysterious, fatal case of pneumonia to Ron Fouchier, a virologist in Rotterdam, Netherlands and to Saudi ministry of health. Fouchier discovered a novel coronavirus in the sample received fromZaki. Zaki posted this on ProMed, the internet mailing list for emerging disease. Within days, a UK hospital discovered an identical case who had also been in Saudi Arabia.
“an investigation team from the Saudi ministry of health arrived at the hospital to investigate me aggressively, threatening me about what I had done,” Zaki told New Scientist. Shaken, he took emergency leave in Cairo – and, he says, was told it was “not safe to come back”. His employment has been terminated.
This was a ‘serious business’ for Saudi Arabia; EU had control over the SARS-CoV-1 chimera [MERS] with evidence that Saudi Arabia was doing illegal research with other countries including India, China and Russia – testing it on unwitting citizens of Saudi Arabia (designed to exclusively target semitic genotypes and indo-asiatic Y-haplogroups). And if you thought Saudi Arabian aggression with a Doctor over following the rules of the kingdom’s Heath Ministry was “strange indeed”, wait, there’s more. Zaki fears that if he had sent samples only to the ministry, they would have been “hidden” – or analysed later by someone else (India, Russia and China, see below).
In 2014, Russian ‘Gamaleya Laboratory’, announced a vaccine for MERS-CoV. Here is the patent of gamaleya:
https://patents.google.com/patent/RU2685185C2/en
https://patents.google.com/patent/RU2016111934A/en
The first human coronavirus was cultivated in 1965 on human ciliated embryonal tracheal cells [3]. Literature about human coronaviruses was limited up until the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-1) outbreak in 2002. The interest in coronaviruses reemerged as a hot topic after MERS-CoV outbreaks. Coronaviruses are enveloped, positive stranded RNA viruses classified as a family within the Nidovirales order. They have a crown appearance under the electron microscope due to the ACE2 spike protein on the surface. The coronavirus subfamily is classified into genera: alpha, beta, gama, and delta. Human coronaviruses belong to Alphacoronavirus (α-CoV), Betacoronavirus (β-CoV).
Five CoVs are known to cause human disease, including:
- β-CoVs
- WIV1-CoV**
- WIV16-CoV**
- SARS-CoV, (a/k/a SARS-CoV-1)
- MERS-CoV (Egypt/2013 strain)
- MERS-CoV-C (Qatar15/2015)
- SARS-CoV-2 (formerly, 2019–nCoV), hence ‘Covid-19’
- HCoV-OC43,
- HCoV-HKU1,
- α-CoVs
- HCoV-229E and
- HCoV-NL63 [35].
NOTE: **These two strains differ from SARS-CoV only in containing an extra open reading frame (ORF) (named ORFX), between ORF6 and ORF7, which has no homology to any known protein sequences; suggesting ORFX was added to provide a region wherein new, more virulent protein sequences (i.e. MERS spike protein or SARS-CoV-2 ACE2 proteins). In other words, WIV1-CoV seems to be an engineered “vessel” awaiting the insertion of a Spike protein RNA segment (MERS, Ebola, Rabies, anthrax, rabies, etc).
Three of these HCoVs are claimed to have spilled over from zoonotic reservoirs. SARS-CoV-1, from 2002, which is claimed by CIA/CDC/NIH/CCP to have emerged from the Chinese horseshoe bat (Rhinolophidae) [26]. HCoV-OC43, which may have emerged from bovine CoV (BCoV) [50], and HCoV-229E [36], which was predicted by molecular clock analysis to share a most recent common ancestor (MRCA) just over 200 hundred years ago with a bat CoV found in the leaf-nosed bat (Hipposideros caffer ruber) bat in Ghana [36]. The link between bat and human CoVs is unsubstantiated speculation (a psyop) that all human, and perhaps mammalian, CoVs may have originated in bats [19, 36, 49].
Human coronavirus NL63 (HCoV-NL63) is an alpha-coronavirus that was first identified in 2004 in the nasopharyngeal aspirate (mucous) from a 7-month-old patient with a respiratory tract infection. Previous studies showed that HCoV-NL63 and the genetically distant severe acute respiratory syndrome (SARS)-CoV employ the same receptor for host cell entry, angiotensin-converting enzyme 2 (ACE2), but it is largely unclear whether ACE2 interactions are sufficient to allow HCoV-NL63 binding to cells. Studies showed that angiotensin-converting enzyme 2 (ACE2) on cells previously resistant to HCoV-NL63 renders them susceptible, showing that ACE2 protein acts as a functional receptor and that its expression is required for infection. However, comparative analysis showed that directed expression or selective scission of the ACE2 protein had no measurable effect on virus adhesion. In contrast, binding of HCoV-NL63 to heparan sulfates was required for viral attachment and infection of target cells, showing that these molecules serve as attachment receptors for HCoV-NL63.
Note to readers: ACE2 protein was proposed as a receptor for HCoV-NL63 already in 2005, but an in-depth analysis of early events during virus infection had not been performed thus far. Here, ACE2 protein is required for viral entry but that it is not the primary binding site on the cell surface. Conducted research showed that heparan sulfate proteoglycans function as adhesion molecules, increasing the virus density on cell surface and possibly facilitating the interaction between HCoV-NL63 and its receptor. Obtained results show that the initial events during HCoV-NL63 infection are more complex than anticipated and that a newly described interaction may be essential for understanding the infection process and, possibly, also assist in drug design.
The perfect binding ability of SARS‐CoV‐2 alphacoronavirus to human cells and the presence of the furin cleavage site, which is new for SARS‐like coronaviruses, might derive from genetic manipulation performed during evolutionary studies (CRISPR manipulation). By combining a bat coronavirus backbone and a receptor binding domain from pangolin coronavirus the resulting chimera would seem “completely natural” (of zoonotic origin). Primarily, two main SARS‐CoV‐2 features stand-out, (1) the presence of a furin cleavage site missing in other CoVs of the same group and (2) a receptor binding domain (RBD) optimized to bind to human cells[ 2 ] might be the result of lab manipulation techniques such as site‐directed mutagenesis. The acquisition of both unique features by SARS‐CoV‐2 more or less simultaneously is less likely to be natural or caused only by cell/animal serial passage.
Wuhan Institute of Virology (WIV) were the first to identify and characterize a new coronavirus (CoV), SARS‐CoV‐2. The genomic sequences obtained from early cases shared 79% sequence identity to the CoVs that caused severe acute respiratory syndrome (SARS‐CoV) in 2002–2003 and 96.2% sequence identity to RaTG13 (MN996532), a CoV sequence detected from a Rhinolophus affinis bat. RaTG13 is currently the closest phylogenetic relative for SARS‐CoV‐2 found,[ 4 ] but its complete genomic sequence was not published before the outbreak of SARS‐CoV‐2 and the original sample was collected in the Yunnan province (China) by the same group of WIV researchers in 2013. Zhou et al.[ 3 ] stated to have found a match between SARS‐CoV‐2 and a short region of RNA‐dependent RNA polymerase (RdRp) of a CoV in their database and then fully sequenced the original sample collected in 2013, which they called RaTG13.
RdRp of RaTG13 has 100% nucleotide identity with the sequence BtCoV/4991 (KP876546), which was identified by Ge et al.[ 5 ] in a Rhinolophus affinis bat in the Yunnan province in 2013, same location and year as RaTG13. BtCoV/4991 was collected in a mine colonized by bats near Tongguanzhen, Mojiang, Yunnan. The WIV researchers were invited to investigate the mine after six miners there had contracted severe pneumonia in 2012iii, and three of the miners have died.[ 6 ] The miners have been tasked with clearing out bat droppings in the mine, and the severity of their pneumonia correlated with the duration of exposure to the mine.
Based on phylogenetic analysis, BtCoV/4991 was the only SARS‐related strain, separated from all known alpha‐ and beta‐CoVs at that time. BtCoV/4991 was also different from other bat CoVs in the phylogenetic analysis carried out by Wang et al. in 2019.[ 9 ] Chen et al.[ 10 ] identified BtCoV/4991 as the closest sequence to SARS‐CoV‐2 because RaTG13 had not yet been published at that time. BtCoV/4991 and RaTG13 have been later asserted to be two different coding names of the same strain, as their original authors at Wuhan Institute of Virology registered the two strains as one entry in the Database of Bat‐associated Viruses (DBatVir).iv
In late July 2020, Zhengli Shi, the leading CoV researcher from WIV, in an email interview [ 11 ] asserted the renaming of the RaTG13 sample and unexpectedly declared that the full sequencing of RaTG13 has been carried out as far back as in 2018 and not after the SARS‐CoV‐2 outbreak, as stated in Zhou et al.[ 3] The reversal in Wuhan’s stance on when exactly RaTG13 was fully sequenced could have been due to the discovery by independent researchers into the origins of SARS‐CoV‐2 that the filenames of the raw sequencing reads deposited by WUhan on May 19, 2020v seem to indicate that sequencing for RaTG13 was done in 2017 and 2018.vi However, no formal erratum about year of sequencing and sample renaming from the authors of Zhou et al. [ 3 ] has yet appeared, or as far as is currently known, has been submitted.
The 2nd non‐human RdRp sequence closest to BtCoV/4991 (91.89% nucleotide identity) is the CoV sequence MP789 (MT084071) isolated in 2019 in a Malaysian pangolin (Manis javanica) from the Guangdong province (GD), China.[12 ] The envelope protein of MP789 shows surprisingly 100% aminoacidic identity with the corresponding protein in RaTG13, in bat‐SL‐CoVZXC21 (MG772934.1), in bat‐SL‐CoVZC45 (MG772933.1) and in some early SARS‐CoV‐2 isolates (e.g. YP_009724392).[13 ] The envelope protein of CoVs is involved in critical aspects of the viral lifecycle, such as viral entry, replication and pathogenesis.[14 ].
Researchers have been chimeric alpha and beta CoVs for over two decades, long before the advent of modern sequencing or genetic engineering techniques. For example, in 1999, a group from Utrecht University used targeted RNA recombination to create a “cat‐and‐mouse” CoV chimera: the RBDs of a feline and murine CoV were swapped, demonstrating that this exchange swapped also species tropism during in vitroexperiments.[ 28 ]
In 2007, the Shi group at Wuhan Institute of Virology created a series of “bat‐man” CoV chimeric spike proteins while trying to determine what exactly confers CoVs the ability to jump from one species to another. The researchers used different segments of the spike protein of the human SARS virus to replace corresponding segments in the spike protein of a bat viral backbone. It was concluded that a relatively short region (aa 310 to 518) of the spike protein “was necessary and sufficient to convert Rp3‐S into a huACE2‐binding molecule,” 29 that is to provide the bat CoV spike protein with a novel ability of binding to a human ACE2 receptor.
In 2008, the Baric group at the University of North Carolina (UNC) took the Wuhan research one step further: instead of using human immunodeficiency viruses (HIV-1) pseudo‐viruses with bat CoV spike proteins, a live chimeric CoV was created. Following the experiments of their 2007 Wuhan colleagues, the Baric group used a bat SARS‐like CoV as a backbone and replaced its RBD with the RBD from human SARS-CoV-1.[ 30 ].
The largest reported number of novel chimeric viruses created was described in a 2017 paper from the Shi group at Wuhan Institute of Virology,[15 ] in which the authors reported creating eight chimeric viruses using WIV1 as a backbone and transplanting into it various RBDs from bat SARS‐like viruses. These viruses were collected over a span of 5 years from the same cave near Kunming, Yunnan Province, where the Shi group originally found Rs3367 and RsSHC014. Only two of the eight live chimeric viruses were successfully rescued, and those two strains were found to possess the ability to bind to the human ACE2 receptor, as confirmed by experiments in hACE2‐expressing HeLa cells and RT‐PCR quantification of viral RNA.
Recombination events between the RBD of CoV from pangolins and RaTG13‐like backbone could have produced SARS‐CoV‐2 as chimeric strain. For such, “naturally occurring” recombination to occur, the two viruses must have infected the same cell in the same organism simultaneously, a rather improbable event considering the low population density of pangolins and the scarce presence of CoVs in their natural populations.x Moreover, receptor binding studies of reconstituted RaTG13 showed that it does not bind to pangolin ACE2.xi.
SARS‐CoV‐2 differs from its closest relative RaTG13 by a few key characteristics. The largest difference is the acquisition in the spike protein of SARS‐CoV‐2 of a cleavage site activated by a host‐cell enzyme furin, previously not identified in other beta‐CoVs of lineage b[36 ] and similar to that of Middle East respiratory syndrome (MERS) coronavirus.[35 ] Host protease processing plays a pivotal role as a species and tissue barrier and engineering of the cleavage sites of CoV spike proteins modifies virus tropism and virulence.[37 ] The ubiquitous expression of furin in different organs and tissues have conferred to SARS‐CoV‐2 the ability to infect organs usually invulnerable to other CoVs, leading to systemic infection in the body.[38 ] Cell‐cultured SARS‐CoV‐2 that was missing the above‐mentioned cleavage site caused attenuated symptoms in infected hamsters,[39 ] and mutagenesis studies have confirmed that the polybasic furin site is essential for SARS‐CoV‐2′s ability to infect human lung cells.
SARS‐CoV‐2 remains unique among its beta CoV relatives not only due to a polybasic furin site at the S1/S2 junction, but also due to the four amino acid insert PRRA that had created it. The insertion causes a split in the original codon for serine (TCA) in MP789 or RaTG13 to give part of a new codon for serine (TCT) and part of the amino acid alanine (GCA) in SARS‐CoV‐2. The insertion of the furin cleavage site in SARS‐CoV‐2 is not consistent with the rest of the sequence, when compared with the MP789 and the RaTG13 sequences (Figure 3). Therefore, it is possible to exclude that such insertion could have originated naturally by polymerase slippage or by releasing and repriming, because insertion mutations generated by these mechanisms have been postulated to maintain the reading frame of the viral sequence.[ 46 ] The possibility that the furin cleavage site could have been acquired by recombination has been questioned by Seyran et al.,[ 47 ] because the SARS‐CoV‐2 spike protein seems to lack any further recombination event in contrast with the recombination model of other CoVs.
The high‐affinity binding of the SARS‐CoV‐2 spike protein to hACE2 could not have been predicted by models based on the RBD of SARS‐CoV. Based on the structural analysis conducted by Wan et al.,[49 ] SARS‐CoV‐2 has the potential to recognize hACE2 more efficiently than the SARS‐CoV, which emerged in 2002. Moreover, generation of CoV chimeric strains, in Wuhan Institute of Virology, has recently demonstrated that bat CoV spikes can bind to the hACE2 receptor with more plasticity than previously predicted.[15 ] All amino acids in the RBD have been extensively analyzed and new models to predict ACE2 affinity are available.[50 ] In this regard, BatCoV Rs3367 (99.9% identity to WIV1) has been shown to share with SARS‐CoV‐2 four out of six critical residues in the RBD. Considering that WIV1 was shown to directly bind to hACE2, the same assumption could easily have been made about SARS‐CoV‐2 RBD.[51 ]
HIV-1 vaccines and Covid-19 vaccines
Antiretroviral therapies capable of controlling HIV-1 replication, rather than completely eradicating HIV-1 virus from patients, catalyzed research initiatives into mRNA vaccines for eradication of AIDS. In other words, current vaccines designed for SARS-Cov-1, MERS-CoV, and SARS-CoV-2 are founded in HIV-1 vaccine research for which Pharma companies insist they deserve to recover via sales of products using mRNA vaccines which intrinsically contain HIV-1 Lipid Nano-Particles. These lipid nanoparticles are best thought of as a tiny, hollow, sphere of fat, into which micro-doses of molecular pharmaceuticals, or mRNA are delivered to very-specific cells.
This is due to discovery of a latent virus reservoir of hard-to-reach ‘nooks and crannies’ of the human body (lymph nodes, brain, fats, calcified nanoparticles); even in resting CD4+ T cells, which persists even in the presence of HAART (antiretroviral treatments). Forced activation of latently infected cells could induce HIV-1 virus production, triggering AIDS, by allowing targeting of the cell (possessing a new marker) by the immune response. A variety of molecules are able to stimulate HIV-1 from latency and exploding into full-blown AIDS. Regardless, HIV-1 Lipid NanoParticles are essential to ferretting those hard-to-find “lurking” viruses, and to do so, it must necessarily trigger activation of those lurking HIV-1 viruses so that molecular packages of pharmaceuticals can recognize a protein and hunt the activated HIV-infected cells, tissue or fluids. It’s a very clever delivery mechanism.
During untreated HIV infection, the majority of infected cells are short-lived: HIV-1 viremia is sustained by a process of unending rounds of de novo infection. Initiation of HAART leads to a dramatic reduction in the levels of viral load and in the frequency of infected cells. Residual viremia persists and can originate from low levels of ongoing replication or, more likely, from the continuous production of viral particles from stable reservoirs. The majority of infected cells in HIV-1+ (on HAART) do not produce viral HIV-1 particles and are defined as “latently HIV-1 infected cells”. Although the production of spliced transcripts or viral proteins is rare, a relatively large fraction of these cells produce short, abortive viral transcripts. Complete silencing of HIV genomes may also occur when epigenetic regulators repress the LTR transcriptional activity, yet, we have not reached this outcome.
But what happens when the molecular pharmaceutical packages are replaced with an mRNA sequence to modify every cell in body to produce specific molecules (transforming humans into bioreactors which can be programmed to produce an abundance, or a nullifying dearth, of chemicals which could be harvested at-will? Further, imagine the HIV-1 lipid nanoparticle activates latent HIV-1 cells which may be dormant, yet undetectable; sudden AIDS cases start showing up in people who had no sexual contact in over 6 months, nor were they needle-users, worse Simian Immunodeficiency Virus (SIV – monkeypox) appears as well. As you’ll see, below, the confluence of these bizarre diseases showing-up where none was present before points a finger at SARS-CoV-2 Vaccines which contained Simian viruses (see table below). Why would this happen?
I conjecture that the HIV-1 lipid nanoparticles are causing suppressed immune systems (due to Covid-19 vaccines containing such) to allow a higher HIV-1 viral load, activated by HIV-1 lipid nanoparticles causing a spectrum of symptoms otherwise diagnostically identical to AIDS – for which mRNA gene-modifying techniques were developed. This suggests that many people may have been unwittingly exposed to HIV-1 yet were asymptomatic due to low viral load and HIV-1 latency; which is South Africa’s rationale for banning Russia’s Sputnik-V vaccine.
First example, of a vaccine containing HIV-1 lipid nanoparticles [Russian vernacular for ‘Lipid nanoparticles’ is “poly-saccharides”], is the Sputnik-V vaccine from Gamaleya Laboratory, Russia. Russian lab, Gamaleya, took an existing MERS-CoV vaccine formula and replaced the spike-protein mRNA of the MERS ACE2 spike-protein, and inserted the mRNA of SARS-CoV-2 ACE2 spike-protein to remove the bioweapon lethality of MERS-CoV. (See below):
Sputnik-V was rejected for use in South Africa precisely because the South African researchers insisted Sputnik-V causes AIDS where none existed; suggesting foreknowledge of the impact of HIV-1 activation upon latent HIV-1. Sputnik-V merges two dissimilar adenovirus-vectored ‘constructs’ based on Adenovirus Type 26 (Ad26) and Adenovirus Type 5 (Ad5); this combination is due to Russians weaponizing the MERS-CoV virus and modulating Ad5 and Ad26 vectors with interchangeable payloads. which pieces are swapped out (for “plausible deniability”. SAHPRA noted that there were concerns about the safety of Ad5-vectored shots in people who are at the risk for HIV infection. I posit the issue isn’t ad5-vectored nor ad26-vectored vaccines, the issue is the residual HIV-1 lipid nanoparticles which compel latent HIV-1,SIV-1, and SARS-CoV-2 to blossom…without a twin process of eradication of HIV-1 itself, once activated via the SARS-CoV-2 vaccine injections.
Where HIV-1 latency is associated with transcriptional latency (i.e., the lack of transcription from the HIV-1 activator), an increasing number of studies indicate that complete silencing of *any* HIV-1 activator is a rare event [33, 34]. A large fraction and possibly the majority of latently infected cells (as defined by cells that do not produce HIV-1 viral particles) may express low levels of short HIV-1 transcripts [34, 35]. Although these abortive transcripts are frequently produced, they rarely elongate enough to generate complete or spliced transcripts (they simply don’t trigger collapse of the human immune system [36]. Production of HIV-1 proteins by latently infected cells appears to be rare but there is a rising (order of magnitude rise) [37, 38]. This suggests that several blocking mechanisms may contribute to the inability of persistently infected cells to produce infectious HIV-1 particles, including blocks in elongation of transcription [36] nuclear export [39], multiple splicing [34] and translation, as detailed below.
Even if the majority of persistently infected cells do not produce viral particles spontaneously, low levels of ‘measurable HIV-1 viral-load (below the limit of detection of commercial assays) can be measured in the majority of patients with latent HIV-1 on HAART [40, 41]. The presence of residual presence of viruses in the blood indicates that a small fraction of persistently infected cells produces viral HIV-1 particles at a given time. As mentioned above, residual presence of viruses in the blood is unlikely to originate from low levels of residual replication, but rather from the production of viral particles from a stable pool of persistently infected cells. Indeed, the small population of viral particles circulating in individuals on HAART is dominated by a predominant plasma clone not found in the latent reservoir, indicating that these virions are unlikely to replenish the persistent reservoir [42, 43]. Residual levels of viruses in the blood show a two-phase decay, suggesting that it may arise from at least two cell compartments, one in which viral production decays over time and a second in which viral production remains stable for at least 7 years. [44]. The source of residual viruses in the blood remains currently unknown. The existence of this “active reservoir” is an additional challenge to the development of effective curative strategies, since it represents a likely cause of viral rebound upon HAART interruption.” https://www.jci.org/articles/view/136227
“Although the HIV reservoir is usually defined as a pool of cells harboring replication-competent (and therefore intact) genomes, several lines of evidence indicate that defective proviruses, even if not capable of replication, have the ability to produce viral transcripts and viral proteins (45, 46). Albeit indirectly, these defective genomes likely contribute to sustained inflammation and T cell activation even after prolonged HAART [47, 48] which may in turn contribute to HIV persistence by promoting the proliferation of infected T cells [49, 50].”
No viral-purging strategy has proven capable of eliminating HIV-1 infection completely or preventing viral rebound if HAART therapy is stopped – novel latency activation approaches are required. Lipid Nanoparticles offer several advantages over more traditional drug delivery methods, including improved drug solubility, stability, and the ability to simultaneously target multiple different molecules to particular cell or tissue types. For example, a lipid nanoparticle was created to demonstrate this point; a novel lipid nanoparticle with the protein kinase C activator bryostatin-2 incorporated (LNP-Bry). These particles can target and activate primary human CD4+ T-cells and stimulate latent HIV-1 virus production from human T-cell lines in vitro and from latently infected cells in a humanized mouse model ex vivo. This activation was enhanced by the HDAC inhibitor sodium butyrate. LNP-Bry can also be loaded with the protease inhibitor nelfinavir (LNP-Bry-Nel), producing a nano-particle capable of both activating latent virus and inhibiting viral spread. Taken together this demonstrates the ability of nanotechnological approaches to provide improved methods for activating latent HIV-1 and provide key proof-of-principle experiments showing how novel delivery systems may enhance future HIV-1 therapy.
Bryostatin-2 was chosen for incorporation into the LNP due to the low effective dosage for latent HIV-1 activation (1–10 nM) as well as the fact that this class of compounds have been widely used in clinical trials exploring its anti-cancer properties [13], [14], [15], [16], [17], [18]; therefore bryostatin preparations could possibly be more rapidly advanced to clinical trial for use in HIV-1 therapy. Bryostatin-2 incorporation was efficient due to its small size (MW = 863 daltons) and hydrophobic nature, which allows it to be readily incorporated into the membrane of the lipid nanoparticles, forming nanoparticles with an average size of 219 nm. Further characterization showed efficient lipid nanoparticles uptake in various cell types. The punctate dots observed in HeLa cells and primary macrophages represent a classical sign of particles localized in cellular compartments such as caveolea pits or early endosomes. The diffuse layer of nanoparticles present in all three tested cell types more likely represents a fusion event where lipid nanoparticles are dispersing into the cellular membranes.
LNP uptake in CEM T-cells was found to be efficient, and proved to be dose, temperature, and time dependent (Fig. 1E–F). The lipid nanoparticles were non-toxic in all cell types tested including peripheral blood mononuclear cells (PBMCs). These data demonstrate the ability of our lipid nanoparticles delivery system to be efficiently taken up into various cell types providing a platform in which we can effectively deliver our cargo of interest, including the HIV latency activator bryostatin-2 and the protease inhibitor nelfinavir.
The pathogenesis of HIV infection and the progression from infection to AIDS vary significantly between exposed individuals. Infection occurs after the virus, which has macrophage (M)- and T lymphocyte (T)-tropic strains and more than 12 subtypes, survives an array of nonspecific, nongenetic environmental and host factors.” https://www.omim.org/entry/609423
Lipid Nanoparticles
Aging is associated with increased morbidity and mortality to viral infections including SARS-CoV-235. Of the multiple factors that contribute to this, impaired vaccine responsiveness and the creation of immunological memory are key contributors; except when manufacturing processes tweak the vaccine ingredients differently. To continue to identify vaccine platforms and adjuvants that strongly promote immune responses in older adults is critically important. Recently, modified mRNA vaccines were approved to control the ongoing pandemic caused by SARS-CoV-2 (COVID-19). These vaccines utilize four-component lipid nanoparticles (LNPs) that have been shown to potently induce IL-1, IL-6 secretion, TFH and GC B cell generation in humans1,10,36,37,38. As more mRNA-LNP vaccines are being designed for other infectious diseases, studies investigating the mechanism of immune modulation including the effect of LNP on innate immunity are critical to improve the efficacy of vaccines in older populations.
Lipid nanoparticles can be synthesized with relative ease, to protect the mRNA against degradation or oxidation, facilitate endosomal escape that can be targeted to the desired cell type by surface decoration with ligands, and as needed, can be codelivered with adjuvants.
HIV-1 Env is an inherently poor immunogen because it has exceptional properties.
“The most optimal HIV-1 purging strategy would involve specific targeting of latently infected cells, but this may prove unachievable because there is no known distinguishing cell surface marker for a cell which is latently infected with HIV-1 [42]. However, it may still be possible to activate only the subset of cells that may harbor the latent infection and in doing so minimize cellular activation of all non-targeted cells. Therefore for this proof-of-concept study we chose CD4 as our target receptor for possible latently infected cells. Targeted particles (LNP-CD4) did indeed target CD4+ cells in a PBMC culture (Fig. 4A–D) when compared with isotype control antibody coated particles (LNP-Iso). As expected LNP-Iso (non-targeting) showed no preference for activating CD4+ or CD8+ T-cells.”
“In sharp contrast, when introduced into a mixed peripheral blood cell culture LNP-CD4 preferentially induced CD69 expression on CD4+ cells with minimal activation of CD8+ cells (Fig. 4E,F). LNP-CD4 was also capable of activating latent HIV-1 in J-Lat 8.4 cells and primary thymocytes (Fig. 4G,H). These data demonstrate the ability of lipid nanoparticles to target and activate latent HIV-1 in CD4+ cells while minimizing cellular activation of non-targeted cells. It’s important to note that when constructing the most optimal in vivo HIV-1 purging strategy, multiple types of lipid nanoparticles that target different cells or tissue types could be used in combination. For example, while CD4-targeting lipid-nanoparticles may be useful in systemic T-cell targeting, unmodified liposomes have been documented to target lymphoid tissue due to their size and drainage into lymphatic vessels [43], [44], [45]. This type of combinatorial approach along with the idea that both latency activators and protease inhibitors will be delivered by the same vehicle may be used to enhance HIV-1 latency purging strategies in vivo.”
“The major cause of acquired immune deficiency syndrome (AIDS) is human immunodeficiency virus type 1 (HIV-1). We have been using evolutionary comparisons to trace (i) the origin(s) of HIV-1 and (ii) the origin(s) of AIDS. The closest relatives of HIV-1 are simian immunodeficiency viruses (SIVs) infecting wild-living chimpanzees (Pan troglodytes troglodytes) and gorillas (Gorilla gorilla gorilla) in west central Africa. Phylogenetic analyses have revealed the origins of HIV-1: chimpanzees were the original hosts of this clade of viruses; four lineages of HIV-1 have arisen by independent cross-species transmissions to humans and one or two of those transmissions may have been via gorillas. However, SIVs are primarily monkey viruses: more than 40 species of African monkeys are infected with their own, species-specific, SIV and in at least some host species, the infection seems non-pathogenic. Chimpanzees acquired from monkeys two distinct forms of SIVs that recombined to produce a virus with a unique genome structure.
“We have found that SIV infection causes CD4+ T-cell depletion and increases mortality in wild chimpanzees, and so the origin of AIDS is more ancient than the origin of HIV-1. Tracing the genetic changes that occurred as monkey viruses adapted to infect first chimpanzees and then humans may provide insights into the causes of the pathogenicity of these viruses”. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2935100/
“The genetic diversity of HIV-1 has continued to increase, which poses an additional challenge to the treatment and prevention of HIV-1 infection [1]. HIV-1 diversity can be attributed to low fidelity of reverse transcriptase in the process of biosynthesis of double stranded DNA, as reflected in its high rate of mutation as well as recombination between different viral strains [2]. Therefore, a large proportion of HIV-1 strains may be defective due to the spontaneous passage of lethal mutations [3]. In long-term non-progressors, levels of HIV-1 defectiveness have been reported to be as high as 64% in accessory genes and 41% in env V3 region [4]. Astonishingly, defective proviruses accumulate rapidly during acute HIV-1 infection to make up over 93% of all proviruses, regardless of how early antiretroviral therapy (HAART) is initiated [5].
“Defective provirus mutants may still play a role in HIV-1 pathogenesis through recombination and rescue of drug resistance phenotypes, and viral recombination may take place with defective viral forms among the quasispecies to increase viral fitness and transmission capacity [6]…The evolution of HIV-1 in the host is complex and subject to the pressure of the immune system. Defective viruses are produced in the process of continuous evolution of HIV-1. However, the role of those defective genes might be converted from junk genes to useful materials as the immune status changed. Defective species can potentially be a part of the HIV-1 reservoir and may contribute over time to fully infectious viral progeny through recombination. Therefore, the existence of the defective HIV-1 promotes the evolution of the virus, increases the diversity of HIV-1 population, and to a certain extent, may affect the immunization effect and the clearance of the HIV-1 reservoir”. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401196/
Schematic overview of the HIV-1 replication cycle in presence or absence of integrase inhibitors. The figure illustrates the main steps in the HIV-1 life cycle divided into an early and a late phase. The early phase includes: the attachment of the virus particle to the CD4 receptor and co-receptors CCR5 or CXCR4; the fusion with the host cell membrane; the uncoating of the viral capsid; the release of the HIV-1 RNA genome and proteins into the cytoplasm; the reverse transcription of the viral RNA genome into a DNA duplex, which has terminal duplications known as long terminal repeats (LTRs); the translocation into the nucleus and the integration into the cell genome. In the nucleus, unintegrated viral DNA is found in both linear and circular forms. The unintegrated circular forms of viral DNA have either one or two LTRs. The linear unintegrated viral DNA is the precursor of integrated proviral DNA, which is a stable structure that remains indefinitely in the host-cell genome. After the integration, the late phase of the cycle starts in which: the proviral DNA is transcribed to form new viral RNA, which subsequently is translated to form viral proteins; these proteins translocate to the cell surface to assemble in the cell membrane and form new viruses. Finally, the new viral particles bud off and are released as mature virions.
Maimonidean Angst 