The Proximal Origin of SARS-CoV-2
http://virological.org/t/the-proximal-origin-of-sars-cov-2/398
Conclusions
In the midst of the global COVID-19 public health emergency it is reasonable to wonder why the origins of the epidemic matter. A detailed understanding of how an animal virus jumped species boundaries to infect humans so productively will help in the prevention of future zoonotic events. For example, if SARS-CoV-2 pre-adapted in another animal species then we are at risk of future re-emergence events even if the current epidemic is controlled. In contrast, if the adaptive process we describe occurred in humans, then even if we have repeated zoonotic transfers they are unlikely to take-off unless the same series of mutations occurs. In addition, identifying the closest animal relatives of SARS-CoV-2 will greatly assist studies of virus function. Indeed, the availability of the RaTG13 bat sequence facilitated the comparative genomic analysis performed here, helping to reveal the key mutations in the RBD as well as the polybasic cleavage site insertion.
The genomic features described here may in part explain the infectiousness and transmissibility of SARS-CoV-2 in humans. Although genomic evidence does not support the idea that SARS-CoV-2 is a laboratory construct, it is currently impossible to prove or disprove the other theories of its origin described here, and it is unclear whether future data will help resolve this issue. Identifying the immediate non-human animal source and obtaining virus sequences from it would be the most definitive way of revealing virus origins. In addition, it would be helpful to obtain more genetic and functional data about the virus, including experimental studies of receptor binding and the role of the polybasic cleavage site and predicted O-linked glycans. The identification of a potential intermediate host of SARS-CoV-2, as well as the sequencing of very early cases including those not connected to the Wuhan market, would similarly be highly informative. Irrespective of how SARS-CoV-2 originated, the ongoing surveillance of pneumonia in humans and other animals is clearly of utmost importance.