SARS-CoV-2 and the Missing Link of Intermediate Hosts in Viral Emergence - What We Can Learn From Other Betacoronaviruses

Abstract

The emergence of SARS-CoV-2 in 2019 has resulted in a global pandemic with devastating human health and economic consequences. The development of multiple vaccines, antivirals and supportive care modalities have aided in our efforts to gain control of the pandemic. However, the emergence of multiple variants of concern and spillover into numerous nonhuman animal species could protract the pandemic. Further, these events also increase the difficulty in simultaneously monitoring viral evolution across multiple species and predicting future spillback potential into the human population. Here, we provide historic context regarding the roles of reservoir and intermediate hosts in coronavirus circulation and discuss current knowledge of these for SARS-CoV-2. Increased understanding of SARS-CoV-2 zoonoses are fundamental for efforts to control the global health and economic impacts of COVID-19.

Global SARS-CoV-2 genomic surveillance: What we have learned (so far)

“…Up to now, different zoonoses have emerged from the Coronaviridae family in the past century ( n = 7), including three responsible for noteworthy human mortality (SARS-CoV, MERS-CoV, and SARS-CoV-2). Those viruses are believed to have originally derived from a bat reservoir species ( Lytras et al, 2022 ; Pekar et al, 2022 ), although several intermediate wild animal species (such as dromedary camel, palm civet, and swine) have been suggested to participate in introduction to human populations, e.g., pangolins for SARS-CoV-2 ( Schindell et al, 2022 ) and camels for MERS-CoV ( Chu, 2015 ; Dudas et al, 2018 ).…”

“…Due to factors such as urbanisation and globalisation, there is currently a wide range of wild, farmed, and domesticated species of animals in close contact with humans across the world, within environments with adequate conditions for transmission (e.g., farms, wild-life trade). During the pandemic, spillback was shown to occur e.g., in domesticated animals such as cats and dogs ( Bienzle et al, 2022 ), urban-related animals such as squirrels (Bosco-Lauth et al, 2021), and farmed animals such as minks and ferrets ( Schindell et al, 2022 ). A notable example was the mid-2020 mink farm outbreak in Denmark that revealed a mink-specific SARS-CoV-2 variant with a combination of mutations not previously described, but that critically included the mutation D614G which had been shown to play a major role in the maintenance of more transmissible lineages among humans ( Larsen et al, 2021 ).…”

Identification of key residues in MERS-CoV and SARS-CoV-2 main proteases for resistance against clinically applied inhibitors nirmatrelvir and ensitrelvir

“…SARS-CoV-1 (Betacoronavirus lineage B) and MERS-CoV (Betacoronavirus lineage C) are known to be enzoonotic in bats and other species such as civets or camels with occasional spillovers into human populations (63,68). Similarly, SARS-CoV-2 (Betacoronavirus lineage B) has most likely been transmitted zoonotically from bats (69)(70)(71)(72)(73)(74). Given that bats are a frequent source of dangerous viruses, we also tested the bat coronavirus HKU9-M pro (Betacoronavirus lineage D) (6,75).…”

SARS-CoV and SARS-CoV -2 cross-reactive antibodies in domestic animals and wildlife in Nigeria suggest circulation of sarbecoviruses

“…The subgenus Sarbecovirus within the Betacoronavirus genus is thought to be one of the youngest subgenera, from which the most recently emerged species Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and SARS-CoV-2 jumped somehow from their original bat host to humans [ 14 ]. In both events, intermediate hosts are thought to have enabled this jump, serving as incubators and propagators for the further evolution and adaptation of the virus to new host species [ 15 , 16 ].…”