Freshly baked, here is presented the Bernd Kaina’s study on the new Coronavirus. The German biologist and toxicologist explains in detail the particularities and the alleged origin of SARS-CoV-2 with the courage that every honest and respectable scientist should have. Kaina’s research has been devoted to DNA damage and repair, DNA damage response, genotoxic signaling and cell death induced by carcinogenic DNA damaging insults. He contributed to more than 300 publications in internationally respected journals and books, so, the German scientist has a quite impressive résumé:
- He identified the repair enzyme O-6-methylguanine-DNA methyltransferase (MGMT) as a protection mechanism against the killing, clastogenic, recombinogenic and carcinogenic effects of alkylating carcinogens;
- He made significant contributions to our understanding of the effects of alkylating carcinogens and chemotherapeutic agents;
- his group studied the importance of DNA repair in drug resistance of glioblastomas, malignant melanomas and other tumour types;
- He contributed to a deeper insight of the mutagenic and cytotoxic effect of UV light, ionizing radiation and chemical genotoxins;
- He assessed the regulation of repair genes and showed that specific DNA repair functions can be induced following genotoxic stress, thus contributing to the cells’ adaptation to these detrimental exposure;
- He demonstrated a repair defect in immunocompetent cells (monocytes);
- He assessed the regulation of repair genes by cytokines;
- He is engaged in studies on the genotoxic effects of TCM drugs such as artesunate.
All roads lead to the laboratory
After having thoroughly evaluated all the zoonotic scenarios (even one without an intermediate host) that could have involved a species jump, the author explains how they do not provide an answer on how a bat virus could have found its way into an intermediate host, be it the pangolin, the cat, or others. Furthermore, he underlines that none of these scenarios answer the question about the origin of the furin cleavage site, the gain of which was obviously a “clonal” event.
Thus, it is assumed that the virus originated from the Wuhan Institute of Virology or the Municipal Institute for Disease Control, which is located in the immediate vicinity of the Huanan wildlife market.
The author analyzes the artificial hypothesis dividing it into 3 different possibilities:
a) The intentional construction through genetic manipulation;
b) The intentional selection in the laboratory for high infectivity in vitro and in the test animal;
c) The accidental evolution and human adaptation of the virus in the laboratory.
And continues explaining that SARS coronaviruses were genetically engineered in several laboratories, including in Wuhan, and chimeric viruses were produced that contained nucleotide sequences from different virus strains (31, 44, 45), but the human SARS-CoV-2 shows no evidence of this type of genetic manipulation; it does not bear signs of gross genetic changes (96.2% identity to RaTG13) and, therefore, does not appear to be a simple fusion product of different viruses. In fact, the changes that make it different from the putative bat progenitor are more subtle. They are technically feasible, so it is more difficult to assess whether options (b) or (c) apply. These scenarios also postulate human involvement and are based on the fact that at the place of origin of the pandemic, in Wuhan, intensive work was and is being carried out on SARS-CoV, involving human cell infection, large-scale virus propagation and experimenting with them in vitro and in experimental animals.
All the unusual properties of the new coronavirus
The Bernd Kaina’s study on the new Coronavirus lists all the unusual properties that need to be considered in substantiating the laboratory hypothesis:
a) The high level of infectivity, the low proportion of infected individuals that became ill, and the low level of lethality (ratio of deceased to ill patients). Thus, the lethality for other coronavirus infections is high (9.6% for SARS/2002; 34.4% for MERS/2012; 40.4% for Ebola; 80.0% for Marburg) compared to COVID-19 (2.1%). High infectivity and symptom-free carriers are expected to favor the spread of infection if a laboratory event happened. The low disease and lethality rate enables the virus to propagate in a cryptic, undetected way in humans.
b) Bat RaTG13 and other SL-CoVs are able to infect human cells directly. The insertion of 12 nucleotides in the spike protein sequence turned the bat progenitor virus (RaTG13 or a similar strain) to a more aggressively growing virus characterized by high ACE2 binding and optimised RBD processing by cellular membrane-bound proteases. Thus, the gain of the PCS/furin cleavage site enhanced the infection rate in human cells.
c) The spike insert sequence of SARS-CoV-2 is present in MERS, with 50% identity on amino acid level and some identity on nucleotide level, which is highly unlikely to be gained accidentally given the degeneration of the code. It is conceivable that coinfection of human cells expressing ACE2 and DPP4 with RaTG13 (or another bat progenitor) with MERS-CoV led to the selection of a hybrid virus that gained through recombination the insert and the furin cleavage site. This is a reasonable process since coronaviruses are highly recombinogenic. As a result, virus propagation would be enhanced in vitro. Thus, without selection pressure, cotransduction experiments with human cells in vitro would lead to a virus strain with improved properties regarding cell entrance and propagation.
d) The presence of a human sequence in the virus genome strongly indicates that SARS-CoV-2 was propagated in human cells before it caused the pandemic.
e) SARS-CoV-2 infection is strongly enhanced by supportive factors such as neuropilin-1 and the proteases MPRSS2 and furin. It is highly unlikely that this complex scenario that facilitates the virus entrance was gained in a single step and in an intermediate animal host. It is more likely that these properties were obtained during virus propagation in human cells, which were engineered (ACE2, DPP4) or in transient transfection experiments in order to improve the conditions for virus entrance. Overall, SARS-CoV-2 appears to be ideally adapted to human cells, which supports the laboratory hypothesis (see the image below).
In conclusion, the Bernd Kaina’s study on the new Coronavirus explain that It should be emphasized that the laboratory hypothesis does not posit that SARS-CoV-2 was genetically engineered on purpose, in simple words “a laboratory construct”. The hypothesis rather states that SARS-CoV-2 is an unintended byproduct of gain-of-function and cotransfection/cotransduction experiments using human (genetically engineered) cell lines in vitro. Selection occurred during virus propagation for a bat virus that is best equipped with tools using supportive factors of human cells and therefore best adapted to humans. There are many conceivable scenarios how transmission could occur in the laboratory, e.g. through aerosols during the work or during handling of waste. Such laboratory events could have occurred repeatedly long before December 2019. They remained undetected because of the cryptic propagation of the virus especially in young people. Nevertheless, a laboratory accident cannot be excluded. In contrast to this, the intermediate host hypothesis rests on many more assumptions. Thus, it is unclear how the virus from nocturnal bats found the way into the intermediate host and how the selection for optimal human propagation could take place there. The intermediate host hypothesis is therefore regarded as less likely.
It’s time for an indipendent international investigation to start.