====== Genetic Engineering Hypotheses of SARS-CoV-2 Origins ======
From essentially the outset of the [[COVID-19 pandemic]], some scientists have pointed to evidence that SARS-CoV-2 came about through [[:gain-of-function]] research. One of the first published papers on the origins of SARS-CoV-2 pointed out reasons to suspect the use of [[serial passage]] through an animal host or cell culture was likely.((August 12, 2020 | Sirotkin and Sirotkin | [[:BioEssays]] | [[https://onlinelibrary.wiley.com/doi/10.1002/bies.202000091|doi.org/10.1002/bies.202000091]]))

===== Genetic Evidence of Engineering =====
Early during the pandemic, scientists compared the SARS-CoV-2 genome to CoVs native to several species. SARS-CoV-2 was most similar per [[:nucleotide]] to bat CoVs, but more similar in [[:codon]] bias to snakes. Simiarity to CoVs from all observed species largely disappeared in the [[:spike protein]] portion of the genome, which is suggestive of a radical divergence from nature.((January 22, 2020 | Wei Ji et al | Journal of Medical Virology | Cross-species transmission of the newly identified coronavirus 2019-nCoV | [[https://onlinelibrary.wiley.com/doi/10.1002/jmv.25682|https://doi.org/10.1002/jmv.25682]])) Karl and Dan Sirotkin published a paper critiquing [[:gain-of-function]] research and exploring molecular and genetic evidence pointing toward likely lab origins.((October, 2020 | Karl Sirotkin and Dan Sirotkin | Bioessays (journal) | Might SARS‐CoV‐2 Have Arisen via Serial Passage through an Animal Host or Cell Culture? | [[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7435492/|doi: 10.1002/bies.202000091]]))

A group of scientists tried and failed to recreate the furin cleavage site through infection.((July 20, 2022 | Adeno News | [[http://adeno-news.com/2022/07/20/scientists-struggles-to-recreate-the-sars-cov-2-furin-cleavage-site-through-infection/|Scientists struggles to recreate the SARS-CoV-2 furin cleavage site through infection]]))

==== Statistical Evidence ====
  * Preprint: Bruttel, Washburne, and VanDongen 
https://www.biorxiv.org/content/10.1101/2022.10.18.512756v1.full


===== Moderna Links =====
[[:Moderna]] holds patents on thousands of genetic sequences under various contexts. There is specific debate over some key sequences.

==== Furin Cleavage Site Sequence ====
On February 21, 2022, scientists published a paper showing a 19 nucleotide portion of the SARS-CoV-2 genome encompassing the furin cleavage site that is a perfect "complementary match to a codon-optimized propriety sequence that is the reverse complement of the human mutS homolog (MSH3)." The paper goes on to say that recombination in an intermedia host (zoonosis) is unlikely.((February 21, 2022 | Balamurali K. Ambati | [[:Frontiers in Virology]] | [[https://www.frontiersin.org/articles/10.3389/fviro.2022.834808/full|doi.org/10.3389/fviro.2022.834808]]))

"A peculiar feature of the nucleotide sequence encoding the PRRA furin cleavage site in the SARS-CoV-2 S protein is its two consecutive CGG codons. This arginine codon is rare in coronaviruses: relative synonymous codon usage (RSCU) of CGG in pangolin CoV is 0, in bat CoV 0.08, in SARS-CoV 0.19, in MERS-CoV 0.25, and in SARS-CoV-2 0.299 (9).

A BLAST search for the 12-nucleotide insertion led us to a 100% reverse match in a proprietary sequence (SEQ ID11652, nt 2751-2733) found in the US patent 9,587,003 filed on Feb. 4, 2016 (10) (Figure 1). Examination of SEQ ID11652 revealed that the match extends beyond the 12-nucleotide insertion to a 19-nucleotide sequence: 5′-CTACGTGCCCGCCGAGGAG-3′ (nt 2733-2751 of SEQ ID11652), such that the resulting mRNA would have 3′- GAUGCACGGGCGGCUCCUC-5′, or equivalently 5′- CU CCU CGG CGG GCA CGU AG-3′ (nucleotides 23547-23565 in the SARS-CoV-2 genome, in which the four bold codons yield PRRA, amino acids 681–684 of its spike protein). This is very rare in the NCBI BLAST database."

===== Biological Attack (Sub)Hypothesis =====
A long and detailed article published in [[State of the Nation]] lays out a case that [[:COVID-19]] was the result of a biological attack on [[:China]] by the U.S.((March 14, 2020 | [[State of the Nation]] | [[https://stateofthenation.co/?p=9167|COVID-19: A Biological Attack on China by the USA]]))

==== Toxins ====
Research report finding [[:toxin]]-like peptides similar to those in animal [[:venom]] (conotoxins, phospholipsases, phosphodiesterases, zinc metal proteinases, and bradykinins) were found in fecal samples from COVID-19 patients, but not in control patients.((October 14, 2021 | Carlo Brogna et al | F1000 Research (journal) | Toxin-like peptides in plasma, urine and faecal samples from COVID-19 patients | [[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8772524/#|doi: 10.12688/f1000research.54306.2]]))