The Evidence which Suggests that This Is No Naturally Evolved Virus A Reconstructed Historical Aetiology of the SARS-CoV-2 Spike

To discover exactly how to attack SARS-CoV-2 safely and efficiently, our vaccine candidate Biovacc-19 was designed by first carefully analysing the biochemistry of the Spike. We ascertained that it is highly unusual in several respects, unlike any other CoV in its clade. The SARS-CoV-2 general mode of action is as a co-receptor dependent phagocyte. But data shows that simultaneously it is capable of binding to ACE2 receptors in its receptor binding domain. In short, SARS-CoV-2 is possessed of dual action capability. In this paper we argue that the likelihood of this being the result of natural processes is very small. The spike has six inserts which are unique fingerprints with five salient features indicative of purposive manipulation. We then add to the bio-chemistry a diachronic dimension by analysing a sequence of four linked published research projects which, we suggest, show by deduction how, where, when and by whom the SARS-CoV-2 Spike acquired its special characteristics. This reconstructed historical aetiology meets the criteria of means, timing, agent and place to produce sufficient confidence to reverse the burden of proof. Henceforth, those who would maintain that the Covid-19 pandemic arose from zoonotic transfer need to explain precisely why this more parsimonious account is wrong before asserting that their evidence is persuasive, most especially when, as we also show, there are puzzling errors in their use of evidence. Introduction: Why does this matter? No-one has ever produced a safe and effective vaccine against a coronavirus. In the context of a forthcoming paper addressing contingency actions cognizant of this fact, the potentialities for 'trained immunity' from 'new old friends' in the form of Bacillus Calmette–Guérin (BCG), Microbacillus vaccae (IMM-102) and most especially Microbacillus obuense (IMM101) by stimulating the innate immune system and especially Delta Gamma T cells are explored; and a salutary review of failed vaccine programmes is included (Kleen et al., 2020). On 28th April 2020, Nature published a graphical guide to eight conceptual approaches featuring in current explorations of around 90 vaccine development programmes intended to counter SARS-CoV-2 (Callaway, 2020). We have just (2nd June 2020) published Biovacc-19 in QRB-Discovery: a candidate vaccine for this daunting task (Sørensen et al., 2020). Its mode of action is unique and therefore is not included in the Nature review. In our paper we gave reasons why the virus vector or RNA vector based approaches that are the basis of the eight methodologies reviewed in Nature are unlikely to prove immunogenic and why either, but especially RNA vectored models, may carry significant risk of Antibody Dependent Enhancement (ADE). As we have detailed in QRB-D, we have seen such a story before over thirty years in the failure of all three mainstream vaccine approaches to HIV, which we predicted but were disbelieved. As with our HIV vaccine, the methodology underpinning Biovacc-19 first analysed fully the virus target. In this case we published the general mode of action for infectivity of SARS-CoV-2. Doing this took us into a fundamental exploration of the biochemistry and structure of the SARS-CoV-2 Spike which is highly singular, possessed of features that we have not seen before and which are not present in other SARS viruses of that clade. We posited that the SARS-CoV-2 general mode of action is as a co-receptor dependent phagocyte. But unusually, simultaneously, data shows that it is capable of binding to ACE2 receptors in its receptor binding domain. In short, SARSCoV-2 is possessed of dual action capability. How do we think this was made possible? That is the subject of this paper. We shall argue from evidence below that the likelihood of this being the result of natural processes is very small. The co-receptor dependent phagocytic general method of action for infectivity and pathogenicity of SARS-CoV-2 appears to be specifically related to cumulative charge resulting from inserts placed on the surface of the Spike receptor binding domain, right next to the receptor binding motif. That SARS-CoV-2 has charged inserts is not in dispute (Zhou et al., 2020) What we have shown that is new is that the SARS-CoV-2 Spike carries significant additional charge (isoelectric point (pI) pI=8.2) compared to human SARS-CoV Spike,( pI = 5.67) and the implications thereof. Basic domains partly inserted, partly substituted amino acids and partly redistributed from outside the receptor binding domain explain the salt bridges formed between the SARS-CoV-2 Spike and its co-receptors on the cell membrane. We comment further on the significance of this in the next section.