Unraveling the Zoonotic Origin and Transmission of SARS-CoV-2

Abstract

The origin and zoonotic transmission route of SARS-CoV-2 remain speculative. We discuss scenarios for the zoonotic emergence of SARS-CoV-2, and also explore the missing evidence and ecological considerations that are necessary to confidently identify the origin and transmission route of SARS-CoV-2 and to prevent future pandemics of zoonotic viruses.

Figure 1

Possible Scenarios for the Origin of SARS-CoV-2. SARS-related coronaviruses (SARSr-CoVs) have been circulating in selected species of bats. It is possible that SARS-CoV-2 remains undiscovered in bats (1). Bats may spread CoVs within bat populations without causing clinical signs of disease (2). Owing to unknown factors, bats may occasionally shed CoVs. Bat SARSr-CoVs may infect humans directly (5) or via an intermediate host (3 and 4), and select for human-adapted strains such as SARS-CoV-2 through adaptive evolution (5; scenario A). A bat SARSr-CoV could have evolved into SARS-CoV-2 in bats before spilling over into humans (5). Alternatively, bat SARSr-CoVs may infect other mammalian intermediate species that remain to be discovered (3) (? indicates an undiscovered intermediate host), and the virus may undergo adaptive evolution in these animals (scenario B). Virus species with enhanced fitness, such as SARS-CoV-2, could then infect humans that are in close contact with the intermediate animal host (4). Pangolins could have been infected with a bat SARSr-CoV, either directly (7) or via an undiscovered intermediate host (8), leading to recombination events between existing pangolin SARSr-CoVs and bat SARSr-CoVs to generate SARS-CoV-2 (scenario C). The recombined virus could have then spilled over into humans (9). Alternatively, pangolins could have been infected with SARSr-CoVs from bats (6 or 7), followed by adaptive or convergent evolution (scenario D) to generate pangolin SARSr-CoVs and/or SARS-CoV-2. Figure created with BioRender.com.