Theories of the origin of SARS-CoV-2 in the light of its continuing evolution.

The exact details of the emergence of SARS-CoV-2, the virus causing Covid-19, remain unknown. Scientific publications using data available to date point to a natural origin linked to the wildlife trade at a market in Wuhan, China. Yet, theories postulating a research-related origin of SARS-CoV-2 abound, and currently dominate the public discussion of the origin of the Covid-19 pandemic. Here, we attempt to characterize the diversity of research-related origin scenarios, discuss their characteristics and evidence base, or the lack thereof, and highlight mutual incompatibilities between some scenarios. We then focus on a feature of SARS-CoV-2 that is central in today's leading research-related hypotheses, namely the insertion that led to the introduction of a polybasic cleavage site in the spike glycoprotein. We examine various scenarios put forward to explain this insertion in a research-related context, and we show how SARS-CoV-2's evolution in humans has provided examples demonstrating that such insertions happen naturally.