SARS-CoV-2 Origins 2–To every thing there is a season, and a time to every purpose under heaven

Attribution is very difficult. Recently several conflicting plausible equivocal hypotheses based on genetic evidence on the mechanism of spillover of SARS-2 have been proposed. One says the virus has been in bats 40-70 years prior to its present form and then spread to humans by happenstance, no intervening animals like snakes or pangolins required. The virus just either evolved a gene for human ACE2 receptor binding by mutation and/or the bats had a similar receptor which evolved toward a human compatible form that selected for better binding among viral mutants. A second hypothesis is that the COVID-19 virus was a result of homologous recombination of two very similar viruses infecting the same host cell in an animal or human. This process is very common in coronaviruses. The enzyme, RNA dependent RNA polymerase can shift between 2 template viral RNAs and yield a hybrid third new virus. However, this same enzyme proof reads the new sequences reducing the probability of mutations and mistakes in replication. Examining the genome of SARS-2 shows recombination has happened in the past. One of these possible bat viruses (the other participant is unknown) is SARSr-Ra-BatCoV-RaTG13. The viruses must have very similar RNA sequences for this to happen. The latter has 96.1% genome identity with SARS-CoV-2. Recently another paper has questioned the validity of the methodology for this observation. The problem with RNA is that the host cell can modify it after replication which can lead to different sequences including changing the sequences of subsequent replicates in the future. Also, genetic and computer mathematical analysis indicates that the region of the genome which determines the cell binding appears to not have undergone homologous recombination. So where are we? We need more than genetic analysis to solve this problem. Viruses must be isolated from natural potential sources. In my tenure in the USAF Counterproliferation Team (1989-2011) l had seen this dilemma before in bacteria and viruses. In anthrax, genetic researchers vehemently declared horizontal gene transfer or homologous recombination of its DNA rarely if ever occurred until we found a hemolytic (breaks down red blood cells) and ampicillin resistant anthrax from a biological warfare plant in Iraq. It was not genetically engineered but only exchanged genetic material with a biological insecticide bacteria grown in the vats between anthrax production as a cover for nefarious activity. Later we discovered this could be accomplished with a synthetic nonproteinaceous virus called a nanobe which transferred ampicillin resistance but also inadvertently activated a silent hemolysis gene by homologous recombination. Later an anthrax-like disease was discovered in equatorial Africa in chimpanzees caused by another bacterium carrying anthrax genes, a natural occurrence of the phenomenon. We also discovered that if a gene for the RNA polymerase of VEE {Venezuelan Equine Encephalitis virus) was placed in a retrovirus crippled so it could not infect and reproduce in cells but only express transferred protein genes, a new complete infectious replicating virus appeared. These examples show the flaw in genetic analysis limited by the assumptions of what can happen and how by genetic natural and artificial manipulation.