On the Origin of SARS-CoV-2: Did Cell Culture Experiments Lead to Increased Virulence of the Progenitor Virus for Humans?

Abstract

We are currently in a rapidly expanding pandemic of the SARS-CoV-2 virus, which originated in the city of Wuhan in central China. The disease COVID-19 is now spread worldwide and has tremendous socio-economic consequences. The origin of the virus can be reconstructed through epidemiological studies and, even more so, from genome comparisons. How the evolution of the virus and the transition to humans might have happened is the subject of much speculation. It is considered certain that the virus is of animal origin and very likely passed from bats to humans in a zoonotic event. An intermediate host was postulated, but many SARS-like bat viruses have the ability to infect human cells directly, which has been shown experimentally by scientists in the Wuhan Institute of Virology using collected specimens containing virus material from horseshoe bats. The propagation of SARS-like bat viruses in cell culture allowed experiments aimed at increasing the infectivity of the virus and adaptation to human cells. This article summarizes the unique properties of SARS-CoV-2 and focusses on a specific sequence encoding the spike protein. Possible scenarios of virus evolution are discussed, with particular emphasis on the hypothesis that the virus could have emerged unintentionally through routine culture or gain-of-function experiments in a laboratory, where it was optimally adapted to human cells and caused cryptic infections among workers who finally spread the virus causing the pandemic.