Human endemic coronavirus emergence in the context of past and recent zoonotic outbreaks

Abstract

Understanding the evolutionary dynamics of the four human endemic coronaviruses might provide insight into the future trajectories of SARS-CoV-2 evolution. We re-assessed the timing of endemic coronavirus emergence and we show that all viruses entered human populations in a time-frame ranging from ~500 to 55 years ago. Because the three highly pathogenic coronaviruses (SARS-CoV, MERS-CoV, and SARS-CoV-2) spilled-over in tight temporal succession, the pattern of coronavirus emergence, in analogy to that of influenza pandemics, is highly irregular. To contextualize this observation in a wider perspective of viral diseases emergence since 1945, we mined epidemiology database information. After controlling for reporting bias, we find that, contrary to widespread beliefs, the occurrence of viral diseases (either zoonotic or not) has not increased over the last decades. Analysis of the recent and ongoing evolution of HCoV-229E and HCoV-OC43 indicated that positive selection most likely contributed to fine-tune the interaction with the human interferon/inflammatory response. Conversely, integration of evolutionary inference and molecular dating provided evidence that these viruses are not undergoing antigenic drift and the temporal emergence of spike protein variants is best explained by optimization of receptor binding affinity. These data provide a fresh look on viral disease emergence and on coronavirus evolution.

Heterologous humoral immunity to human and zoonotic coronaviruses: Aiming for the achilles heel

“…Nevertheless, the fact that multiple HCoVs are concurrently endemic highlights the limits of heterologous immunity and further suggests that it played a limited role during the initial introduction of HCoVs into humans. For example, molecular clock analysis of the HCoV-OC43 S gene indicated a relatively recent zoonotic introduction, dating to around 1890 [ 114 ], whereas other HCoVs are estimated to have been introduced much earlier [ [115] , [116] , [117] ]. Therefore, HCoV-OC43 appears to have successfully established endemic infection in humans and is even hypothesised to have caused the 1889–1890 pandemic [ 114 ] despite the pre-existence of other HCoVs [ 117 ].…”

“…For example, molecular clock analysis of the HCoV-OC43 S gene indicated a relatively recent zoonotic introduction, dating to around 1890 [ 114 ], whereas other HCoVs are estimated to have been introduced much earlier [ [115] , [116] , [117] ]. Therefore, HCoV-OC43 appears to have successfully established endemic infection in humans and is even hypothesised to have caused the 1889–1890 pandemic [ 114 ] despite the pre-existence of other HCoVs [ 117 ]. The same can also be argued for all endemic and new pandemic CoVs that were introduced in humans after the first endemic HCoV was established.…”

“…It is interesting to note, however, that the estimated order in which HCoVs first emerged in humans may be related to the degree of heterologous immunity they each elicit. In the alphacoronaviruses, HCoV-NL63, which has been suggested to induce stronger heterologous immunity against HCoV-229E than HCoV-229E does against HCoV-NL63 [ 11 ], is estimated to have emerged after HCoV-229E [ 117 ]. Similarly, in the betacoronaviruses, HCoV-OC43, which is thought to induce stronger heterologous immunity against HCoV-HKU1 than HCoV-HKU1 does against HCoV-OC43 [ 11 , 108 ], is estimated to have emerged after HCoV-HKU1 [ 117 ].…”

“…In the alphacoronaviruses, HCoV-NL63, which has been suggested to induce stronger heterologous immunity against HCoV-229E than HCoV-229E does against HCoV-NL63 [ 11 ], is estimated to have emerged after HCoV-229E [ 117 ]. Similarly, in the betacoronaviruses, HCoV-OC43, which is thought to induce stronger heterologous immunity against HCoV-HKU1 than HCoV-HKU1 does against HCoV-OC43 [ 11 , 108 ], is estimated to have emerged after HCoV-HKU1 [ 117 ]. The ability to escape heterologous immunity elicited by their respective, pre-existing genus member may have contributed to the successful establishment of HCoV-NL63 and HCoV-OC43 in humans.…”

Bioinformatic identification of Endemic Coronaviruses’ epitopes in SARS-CoV-2 genomes isolated in Kenya

“…These viruses entered human populations between 500 to 55 years ago, and their evolutionary dynamics provide insights into the potential future trajectories of emerging coronaviruses like SARS-CoV-2 3 . Understanding the emergence, immunity and evolution of both endemic and emerging coronaviruses is essential for comprehensive preparedness and response strategies to combat the ongoing and potential future threats posed by these viruses 4,5 .…”