User:Bakkster Man/Origin Sandbox

COVID-19 Origin Hypotheses

There are multiple proposed explanations for how SARS-CoV-2 was introduced into, and evolved adaptations suited to, the human population. There is significant evidence and agreement that the most likely original viral reservoir for SARS-CoV-2 is horseshoe bats, with the closest known viral relative being RaTG13. The evolutionary distance between SARS-CoV-2 and RaTG13 is estimated to be between 20 and 90 years, which each origin hypothesis attempts to explain in a different way. These scenarios continue to be investigated in order to identify the definitive origin of the virus.

The most direct pathway of introduction is direct zoonotic transmission (also known as spillover) from the reservoir species to humans. Human contact with bats has increased as bat habitats and human population centers encroach on one another, creating additional opportunities for spillover. Bats are a significant reservoir species for a diverse range of coronaviruses, and humans have been found with antibodies for them suggesting that this form of direct infection by bats is common. In this scenario, the direct ancestor of SARS-CoV-2 remains undiscovered in bats.

In addition to direct spillover, another pathway is that of transmission through an intermediate host. Specifically, this implies that a cross species transmission occurred prior to the human outbreak and that it had pathogenic results on the animal. This pathway has the potential to allow for greater adaptation to human transmission via animals with more similar protein shapes to humans, though this is not required for the scenario to occur. The evolutionary separation from bat viruses is explained in this case by the virus' presence in an unknown species with less viral surveillance than bats. The virus' ability to easily infect and adapt to additional species (including mink) provides evidence that such a route of transmission is possible.

Another proposed introduction to humans is through fresh or frozen food products, referred to as the cold/food chain. This scenario's source animal could be either a direct or intermediary species as described above. Many investigations centered around the Huanan Seafood Wholesale Market in Wuhan, which had an early cluster of cases. While there have been food-borne outbreaks of human viruses in the past, and evidence of re-introduction of SARS-CoV-2 into China through imported frozen foods, investigations found no conclusive evidence of viral contamination in products at the Huanan Market.

The final scenario is the introduction of the virus to humans through a laboratory incident. The Wuhan Institute of Virology has performed research into bat coronaviruses since 2005, aiming to understand the source of the 2002–2004 SARS outbreak, and identified the RaTG13 virus which is the closest known relative of SARS-CoV-2. The proximity of the laboratory to the initial outbreak has lead some to speculate as to it being the entry point. RaTG13 was sampled from bats in Yunnan (located roughly 1,300 km away from Wuhan), and there are relatively few bat coronaviruses from Hubei province. Deliberate bioengineering of the virus has been ruled out, with remaining investigations considering the possibility of a collected natural virus inadvertently infecting laboratory staff during the course of study.

Other info

According to biotech entrepreneur Yuri Deigin, coauthor of a scientific paper on the laboratory scenario, "The biggest coincidence is this [initial outbreak] happening in Wuhan, next door to the number one lab in China on coronaviruses. This [proximity] coincidence hasn't been explained at all". Deigin also said that "Wuhan is a very odd place for a bat coronavirus spillover to ocurr because, first of all, they don't eat bats in Wuhan or Hubei, as opposed to the South of China, where it is part of the cuisine.". He stated that "those bats that cause the coronavirus they don't live anywhere near Wuhan, they live 2,000 km away in Yunnan". Direct citation to Deigin/Segreto study (doesn't appear to be peer-reviewed)..

From a genomic perspective, Lau et al (2020) comment on some abnormal features of SARS-CoV-2 (i.e. its evolutionarily-distinct RBD and the insertion of S1/S2 cleavage site which is very rare among Sarbecovirus species) acknowledging that they may have "raised the suspicion of an artificial recombinant virus". However, other than these observed peculiarities, the authors say "there is currently no evidence showing that SARS-CoV-2 is an artificial recombinant, which theoretically might not carry signature sequences" and conclude that "further surveillance studies in bats are needed to identify the possible source and evolutionary path of SARS-CoV-2."