The origin of SARS-CoV-2

Ivan Toplak
University of Ljubljana, Veterinary Faculty, Institute of Microbiology and Parasitology, Virology Unit, Ljubljana, Slovenia
Ivan.Toplak@vf.uni-lj.si

Coronaviruses (CoV) are divided into four genera: alpha-, beta-, gamma- and delta-CoV. When a virus passes from animals to humans for the first time it is called a spillover event. A virus that is regularly transmitted from an animal to a human is called a zoonotic virus.

Severe acute respiratory syndrome virus (SARS-CoV-2), the etiological agent of the current COVID-19 pandemic, which first detected in December 2019 in Wuhan, China, is the seventh coronavirus known to infect humans. Identifying the origin of SARS-CoV-2 may help us to avoid future epidemics of coronavirus and other zoonoses.
Three possible scenarios that were discussed as the origin of SARS-CoV-2 are (i) natural selection in an animal host before zoonotic transfer, (ii) natural selection in humans following zoonotic transfer and (iii) “a laboratory escape”. Based on nucleotide comparison of closely related genomes, structural studies and biochemical experiments, SARS-CoV-2 have a receptor-binding domain (RBD) that binds with high affinity to angiotensin converting enzyme II (ACE2) from humans, ferrets, cats and other species with high receptor homology.

The second notable feature of SARS-CoV-2 is a polybasic cleavage site (RRAR) at the junction of S1 and S2, the two subunits of the spike protein. This allows effective cleavage by furin and other proteases and has a role in determining viral infectivity and host range. It is not very likely that SARS-CoV-2 emerged through laboratory manipulation of a related SARS-CoV-like coronavirus. All SARS-CoV-2 genomes sequenced so far have the same genomic features and are thus derived from a common ancestor. The available evidence suggests that SARS-CoV-2 has a natural animal origin and is not a manipulated or constructed virus.

SARS-CoV-2 virus most probably has its ecological reservoir in one or more species of bats, which still need to be determined.