CLEAR EVIDENCE it is NOT a Bioweapon. So What’s All This About ACE2 and nCoV-2019 (COVID-2019)?

LIVING IN THE LAND OF ABJECT OBJECTIVITY, as a truly independent scientist, I see streams of information from a wide and diverse number of sources. It’s also a cozy little spot where arrows of bias from “both sides” of every issue are flung with remarkable ease – and with little consideration for liability over unwarranted attempts at defamation.

Of course, some would say I’ve “defamed” myself merely by admitting that vaccines can harm, and vaccines can kill – as if that’s (a) not true, and (b) a reality that is so taboo that anyone who dares breathe a word of it is fair game for the slightest expression of hate (such as name-calling) and outright accusations of being a fraud.

Peanut gallery managers who do little to actually effect change in a positive manner, enjoy the chance to bully someone with, apparently, society’s blessings. “Hit ’em harder!” “Well done!” Except everything I publish is backed by experiment, if not that, by observational studies, if not that, by summary statistics, if not that, by initial observersations leading to Science. Their habit of following objective scientists around is a mere annoyance.

COVID-2019?

World Health Organization (WHO) has renamed the virus SARS-CoV-2, and the disease it causes COVID-2019. The classification of viruses should ideally reflect their phylogenetic relationships and especially inherited genetic capacity for pathogenicity [thx reader for the update on the name]. But that would require a deep understanding of the evolutionary history of the functional elements contributing to the virulence and transmissibility of viruses – something that public health officials and run-of-the-mill MDs are too distant from to understand.

For the last week, I’ve been analyzing the motif patterns in B-CoV’s, and as a result of that, having settled the issue that pShuttle-SN is not likely to have been involved in the origin of COVID-19, and furthermore that no recombinant B-coronavirus for which we have data is likely to be ultimately found to be the ancestor of COVID-19 (in review), it’s time to look at another claim about the virus now raging: ACE2.

ACE2

A paper, “The novel coronavirus 2019 (2019-nCoV) uses the SARS-coronavirus receptor ACE2 and the cellular protease TMPRSS2 for entry into target cells”, published on bioRxiv, examined SARS 2 (new name for 2019-nCoV) cell entry using pseudoviruses made (using recombinant technology) that express the SARS 2 spike protein, which is used by SARS 2 to gain entry into cells. The pseudoviruses were made using vesicular stomatitis virus (VSV) particles. The authors of the study evaluated the abilty of these pseudoviruses to enter a variety of human and animal cell lines under different experimental conditions.

Their experiments and analysis found that SARS 2 Spike protein binds to angiotensin-converting enzyme 2 (ACE2), and that it uses a cellular protease called TMPRSS2 to activate, or “prime” viral fusion and entry into cells.

This means that TMPRSS2 might be potentially useful therapeutic target for the treatment and prevention of SARS 2 entry into cells. One such candidate is camostat mesylate, a known TMPRSS2 inhibitor. Camostat mesylate is approved for human use in Japan.

The authors also noted that serum from a convalescent SARS-CoV patient neutralized S-protein mediated entry into cells. This means that survivors of the infection may be a useful source of biologics to help others who are infected survive or avoid critical illness. The rate of critical illess of COVID-19 in China is staggering.

It’s important to note that the SARS 2 Spike protein uses a different cellular entry receptor from MERS-CoV, which uses human DPP4. Also, the seasonal coronavirus uses 229E (human APN), and that other coronaviruses, including SARS and HCoV-NL63, use ACE2 to enter cells. The finding that COVID-2 has especially strong binding capacity to ACE2 is consistent either with recent adaptation for living in humans, or for older adaptation in the wild to a mammal that has ACE2 structures that resemble humans.

ACE2 has other roles in the body has well; gene expression data tell us that it plays a role in the regulation of cardiovascular and renal function, as well as fertility (Refseq).

IS COVID-2019 DESIGNED TO SPECIFICALLY ENTER VIA ACE-2 TO “TARGET” ASIANS?

So, clearly there are important positions that people can take in the area of international intrigue. In the area of bioweapons rumors, Western countries like the US and Canada have touted the idea that COVID-19 might be a bioweapon that escaped. In China, far-right groups are touting that the virus was made by the US and is an attack on the Han people.

Polymorpisms certainly exist in the ACE locus, and earlier studies found differences among Asians, Caucasian, and people of African descent with respect to the frequencies of two alleles – the D and I alleles. Alleles combine in pairs to make genotypes (one from mom, one from dad), and the meta-analysis reported that the II, ID and DD genotypes were found at 22.5% II, 47% ID, and 30.5% DD. (As an aside, here’s a handy Hardy-Weinberg calculator to test for HW-Equilibrium to see if there’s anything ususual about this distribution that might lead to a hypothesis of ongoing selection. For those who like to do such things).

The specific D allele frequency found across ethnic groups were 39.1% in Asians, 56.2% in Caucasians, and 60.3% people of African descent. (For those who may not know, the corresponding I allele frequency) would be 100%-D for each ethnic group).

This distribution of genotype and alleles of the ACE gene would be a TERRIBLE target for a bioweapon that is alleged to target Asians for obvious reasons: it would end up targeting a huge proportion of the rest of the world, and the “home” population, whichever side targeted people based on their ACE genotype.

So, without bothering to condescend to those who thought that somehow ACE was so different in Asians that a bioweapon has been masterminded and has been recently, I am very happy to say that the likelihood of this from a purely strategic standpoint is nil. (NB: ACE is a different gene from ACE2, see article addressing this here).

Since recombination in nature is not a likely explanation of the massive morbidity and mortality of COVID-19 from SARS 2, and recombination technology was not used to create this, and it is not a US Bioweapon that backfired, nor a Chinese bioweapon that backfired, we still need to wonder: why is the mortality and critical illness from COVID-2019 in the Wuhan district so high in comparison to that seen in the rest of the world so far?

Another possibility is high ambient exposure to bat coronaviruses. People in the region, however, have been eating wild-caught animals for thousands of years. Since China has such an exceptional written history going deep into their past, it would behoove humanity to study the ancient scrolls from China for evidence of plagues traced to eating bats, pangolins and other animals we now know understand can harbor coronaviruses. It is likey that B-coronaviruses have been infecting humans for tens if not hundreds of thousands of millenia.

So what’s different in 2019? On Dec 1, a new national vaccine law went into effect. “China is to implement a state immunization program, and residents living within the territory of China are legally obligated to be vaccinated with immunization program vaccines, which are provided by the government free of charge. Local governments and parents or other guardians of children must ensure that children be vaccinated with the immunization program vaccines (art. 6).”

The first reported case of COVID19?

December 1, 2019.

In my first article on the origins of the virus, I mentioned that one way to get hundreds of thousands super sick from a coronavirus is to have sensitized the population with a vaccine containing a spike protein. Why? Because prior animal studies showed high mortality following re-challenge in vaccinated animals. See studies, below.

References

Staessen, J., Ginocchio, G., Wang, J. G., Saavedra, A. P., Soubrier, F., Vlietinck, R. & Fagard, R. (1997). Genetic variability in the renin-angiotensin system: prevalence of alleles and genotypes. Journal of Cardiovascular Risk 4, 401–422.

Te et al., 2012. Immunization with SARS coronavirus vaccines leads to pulmonary immunopathology on challenge with the SARS virus. PLoS One 7(4) https://www.ncbi.nlm.nih.gov/pubmed/22536382

Tseng et al., 2012. Double-Inactivated Severe Acute Respiratory Syndrome Coronavirus Vaccine Provides Incomplete Protection in Mice and Induces Increased Eosinophilic Proinflammatory Pulmonary Response Upon Challenge https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3209347/

Yasui et al., Prior immunization with severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) nucleocapsid protein causes severe pneumonia in mice infected with SARS-CoV. J Immunol. 181:6337-48 https://www.ncbi.nlm.nih.gov/pubmed/18941225 https://www.jimmunol.org/content/181/9/6337.long