Study on sentinel hosts for surveillance of future COVID-19-like outbreaks | Scientific Reports

Scientific Reports volume 14, Article number: 24595 (2024) Cite this article Metrics details The spread of SARS-CoV-2 to animals has the potential to evolve independently. In this study, we

Scientific Reports volume 14, Article number: 24595 (2024) Cite this article

Metrics details

The spread of SARS-CoV-2 to animals has the potential to evolve independently. In this study, we distinguished several sentinel animal species and genera for monitoring the re-emergence of COVID-19 or the new outbreak of COVID-19-like disease. We analyzed SARS-CoV-2 genomic data from human and nonhuman mammals in the taxonomic hierarchies of species, genus, family and order of their host. We find that SARS-CoV-2 carried by domestic dog (Canis lupus familiaris), domestic cat (Felis catus), mink (Neovison vison), and white-tailed deer (Odocoileus virginianus) cluster closely to human-origin viruses and show no differences in the majority of amino acids, but have the most positively selected sites and should be monitored to prevent the re-emergence of COVID-19 caused by novel variants of SARS-CoV-2. Viruses from the genera Panthera (especially lion (Panthera leo)), Manis and Rhinolophus differ significantly from human-origin viruses, and long-term surveillance should be undertaken to prevent the future COVID-19-like outbreaks. Investigation of the variation dynamics of sites 142, 501, 655, 681 and 950 within the S protein may be necessary to predict the novel animal SARS-CoV-2 variants.

The COVID-19 pandemic, which began in 2019, has had a significant impact on the global economy and public health. As of 30 July 2023, more than 768 million confirmed cases and more than 6.9 million deaths had been reported worldwide1. The pathogen, SARS-CoV-2, is a single, positive-stranded, non-segmented RNA virus, and the viral genome can encode at least 29 proteins, of which the spike (S) protein is a critical structural protein involved in recognition and fusion with the host cell receptor angiotensin-converting enzyme 2 (ACE2)2,3. The S protein is composed of two functional regions, S1 and S2. The S1 region contains two crucial structural domains, the N-terminal domain (NTD) and the receptor-binding domain (RBD), which interfere with the immune response of the host cell and recognize and bind to host-associated receptors, respectively, while the S2 region mediates the fusion of the virus with the cell membrane4,5,6. It has been demonstrated that the high variability of the RBD and NTD relates to the virus’ immune evasion and host selection7.

Coronaviruses have a taxonomically and geographically broad host range and exhibit genetic diversity and frequent gene recombination. Mammals are important potential hosts for cross-species transmission of novel coronaviruses. SARS-CoV-2 is widely believed to have originated in bats8,9,10, and previous studies have suggested that pangolins were likely to be its intermediate host due to their high amino acid sequence similarity11,12,13. However, later studies found that their nucleotide sequence was clearly different, so the conclusion that pangolins are intermediate hosts was not conclusive14. Since the outbreak of the COVID-19 pandemic, numerous infections have been observed in both domestic and wild mammals. Various mammals such as cats, dogs, white-tailed deer, lions and tigers can be infected with SARS-CoV-2 under natural conditions and become potential hosts for the virus15,16,17. Due to the need to adapt quickly to new hosts, transmission between different host species often leads to rapid variation or evolution18. Although the epidemic intensity of COVID-19 in humans has recently declined, the spread of SARS-CoV-2 in these domestic and wild animals remains a major threat and they may at any time cause a re-emerging outbreak, especially considering the possible presence of other SARS-like-CoVs in these animals as well as frequent genetic recombination19, which has raised further concerns about the emergence and re-emergence of coronaviruses. Identifying sentinel hosts for surveillance is important for effective control of infection and transmission of SARS-CoV-2 or other SARS-like-CoVs. In this study, we classified animal hosts into four taxonomic hierarchies of species, genus, family and order, and compared the amino acid sequences of the human SARS-CoV-2 S protein with those of nonhuman mammals to identify critical polymorphic sites and perform phylogenetic and selective pressure analyses. We attempt to identify the sentinel animals that need to be closely monitored and the natural reservoir of SARS-CoV-2 in order to prevent an unexpected pandemic in the future.

In addition to humans, a total of 6 orders, 14 families, 20 genera and 31 species of SARS-CoV-2 hosts were included in this study (Fig. 1).

Nonhuman mammalian hosts of SARS-CoV-2 and their taxonomic hierarchies. All hosts included in this study are mammals, and the taxonomic hierarchies of order, family, genus and species are shown in green, purple, yellow and blue respectively. In total, 6 orders, 14 families, 20 genera and 31 species were included. The star indicates mammalian hosts from which the majority of amino acids in the RBD of SARS-CoV-2 did not differ from those derived from humans.

The phylogenetic tree of the S gene showed a strong tendency for SARS-CoV-2 to cluster according to epidemic area and host species, and a moderate tendency for temporal clustering. The viruses isolated from different hosts in the early phase can be clustered on the phylogenetic tree according to host species. Sequences from domestic dog (Canis lupus familiaris), domestic cat (Felis catus), mink (Neovison vison), and white-tailed deer (Odocoileus virginianus) showed a closer relationship to the reference, whereas sequences from the genera Manis and Rhinolophus were located at the root of the tree (Fig. 2A). Indeed, both before and after the pandemic, viruses from the genera Manis and Rhinolophus were distant from the reference (Fig. 2B, C, F, G), but for viruses isolated from other hosts, the trend of clustering based on host species was broken on the phylogenetic trees during the later phase of the pandemic, with sequences from each species dispersed and shifting from host species clustering to predominantly endemic area clustering (Fig. 2D, E). Sequences from the genus of Panthera were also distant from the reference (Fig. 2A, D, E). Unlike most other hosts, whose viruses tended to cluster separately during the early phase and then mix, the lion (Panthera leo) sequences consistently formed a distinct cluster both early and late phases of the pandemic (Fig. 2A, D, E). It is not easy to determine whether the lion-derived virus originated in humans during the pandemic or had circulated previously. It can therefore be confirmed that, with the exception of SARS-CoV-2 isolated from pangolins, bats and lions, the viruses isolated from other hosts all originated from human epidemic spillover infections.

Phylogenetic trees of SARS-CoV-2 spike (S) protein genes. No more than 20 earliest sequences from each species were retained to construct the overall phylogenetic tree (A). Due to the large gap between sequences from pangolin or bat and human sources, unrooted trees were constructed separately: pangolin-derived (B) and bat-derived (C). The phylogenetic trees of S protein sequences with similarity less than 0.9965 were constructed according to the time of sequence collection before 2020 and after 2020: phylogenetic tree of the complete S protein sequence after 2020 (D), phylogenetic tree of the NTD and RBD regions after 2020 (E), phylogenetic tree of the complete S protein sequence before 2020 (F), phylogenetic tree of the NTD and RBD regions before 2020 (G).

Manis and Rhinolophus are two host genera worth investigating. On the pre-2020 phylogenetic trees, compared with the Manis genus sequences, the Rhinolophus genus sequences are closer to the human reference sequence, and the closest is the bat coronavirus RaTG13 from a Chinese horseshoe bat (Rhinolophus affinis) in Yunnan (Fig. 2F, G). Sequences from the Manis and Rhinolophus genera were both distant from the human sequences, suggesting that although it cannot be ruled out that the viruses they carry are of human-origin, they are more likely to serve as natural hosts and provide a persistent SARS-like-CoVs reservoir for infection. The identities of them are shown in Supplementary Table S1, S2.

There were seven hosts in the species hierarchy, i.e., small-clawed otter (Aonyx cinereus), lion, tiger (Panthera tigris), Roborovski hamster (Phodopus roborovskii), golden hamster (Mesocricetus auratus), European mink (Mustela lutreola), ferret (Mustela furo), with significant difference sites, of which lion had the largest number of statistically significant differential majority of amino acids (9), with seven of them located in the key NTD or RBD (Fig. 3). In the hierarchy of genus, Panthera, Mesocricetus, Mustela, Aonyx and Phodopus had statistically significant differential majority of amino acids in the key NTD or RBD. A total of 15 statistically significant differential amino acid sites were identified across species, genus, family and order, of which eight were located in the NTD (19, 69, 95, 142, 144, 156, 157 and 158), four in the RBD (452, 478, 486, 501) and one in the furin protease cleavage site (Table 1). In the host taxonomic hierarchy of species, sites 452, 478, 486, and 501 of the S protein showed lower conservation (Fig. 4). In all host taxonomic hierarchies, RBD is more variable than NTD (Supplementary Fig. S1, S2). Detailed results of the differential majority of amino acids in four host taxonomic hierarchies are given in Supplementary Tables S3-S6.

Graph of SARS-CoV-2 S protein amino acid polymorphism in species of the host taxonomic hierarchy. The red font indicates that the majority of amino acid residues in the SARS-CoV-2 S protein from that species differed from those in humans at those positions, e.g. L5F indicates that the majority of amino acids in the SARS-CoV-2 S protein sequence from the small-clawed otter (Aonyx cinereus) differed at 5 positions from the human-derived SARS-CoV-2 sequence, which was varied from L (leucine) to F (phenylalanine). Lion (Panthera leo) had the largest number of statistically significant different majority amino acid residues (9), seven of which were in the NTD or RBD.

SeqLogo of amino acid substitutions in SARS-CoV-2 S protein in different taxonomic hierarchies of the mammalian hosts. Sequence logos of conserved majority of amino acid from species (a), genera (b), families (c) and orders (d) are shown. Sites where the majority of amino acid of the S protein differ significantly from those of human-acquired viruses in that taxonomic hierarchy are marked in red. The height of each letter in the figure is proportional to the frequency of occurrence of the corresponding amino acid residue at that position, and the letters at each position are arranged in order of conservation from large to small, with the top letters representing conserved sequences.

Viruses isolated from domestic dog, domestic cat, mink, and white-tailed deer showed typical characteristics of those from humans in terms of amino acid polymorphism. The viral S protein from these animals showed no differences in the majority of amino acid compared with the full-length reference. The protein from the lion exhibited again much more divergent sites from the human-derived sequences, only next to those from the genera of Manis and Rhinolophus (Table 2).

FUBAR detected more positively selected sites than SLAC. In the species hierarchy, three host animals, mink, domestic dog, and green monkey (Chlorocebus sabaeus), had positively selected sites searched by SLAC, with the numbers of 3, 3, and 2, respectively, while FUBAR detected more positively selected sites, with a total of 14 species having positively selected sites. Combining the two methods, the top four species with the highest number of positively selected sites were domestic dog, domestic cat, mink and white-tailed deer with 42, 28, 21 and 18, respectively (Fig. 5). These results suggest that although SARS-CoV-2 in these animals originated from human spillover during the pandemic, it retains significant mutational potential during its circulation and may give rise to novel variants in the future. Lion, closely following the four species above, showed a total of 8 positively selected sites, 6 of which were in critical regions such as RBD and NTD using the FUBAR method. In the genus hierarchy, the top five genera with the highest number of positively selected sites were Canis, Felis, Neovison, Odocoileus, and Panthera. Among these, Canis, Neovison, and Panthera had significant positively selected sites by both methods, including key sites such as 501 and 681. In particular, the genus Panthera not only had positively selected sites by both methods, but also had statistically significant differential majority amino acid residues in key regions such as the RBD, NTD and the furin protease cleavage site. In the taxonomic hierarchies of species, genus and order, and by the FUBAR method, the five positively selected sites with the highest frequency are 681, 501, 142, 222, 655; 681, 501, 142, 655, 950; and 681, 501, 655, 478, 18 respectively (Supplementary Table S7). When combined across three taxonomic hierarchies, the five positively selected sites with the highest frequency are sites 681, 501, 142, 655 and 950. Tracking the variation dynamics of these sites may be necessary to predict the novel animal-origin variants of SARS-CoV-2.

Graph of the number of positively selected sites in the S protein of SARS-CoV-2 in different mammalian taxonomic hierarchies. The graph shows the number of positively selected sites of different species, genera and orders using the two methods of FUBAR and SLAC. The domestic dog (Canis lupus familiaris), domestic cat (Felis catus), mink (Neovison vison) and white-tailed deer (Odocoileus virginianus) have the most positively selected sites using the FUBAR method.

Since the beginning of the COVID-19 pandemic, the range of infected animals has expanded to an unprecedented extent. There is a significant risk that they could transmit SARS-CoV-2 back to humans. Identification of sentinel animals for epidemic surveillance is critical to control emerging or re-emerging outbreaks caused by novel SARS-CoV-2 variants or other SARS-like-CoVs. In this study, based on a large-scale bioinformatic analysis of viral genomes from human and nonhuman mammals, we identify domestic dog, domestic cat, mink, and white-tailed deer as well as their respective genera as the sentinel hosts that require special attention to prevent them from transmitting an evolved SARS-CoV-2 variant back to humans and causing a re-emerging outbreak. The genera Panthera (especially lion), Manis and Rhinolophus are proposed to be monitored for potential emerging outbreaks caused by other SARS-like-CoVs. In addition, it is recommended that the variation dynamics of sites 142, 501, 655, 681 and 950 within the S protein be studied to predict the novel variants of SARS-CoV-2 originating from animals.

Animals in close contact with humans, whether as pets or as a source of fur or food protein, have increasing opportunities to share and exchange pathogens with humans. In this study, in the species taxonomic hierarchy, the S protein of SARS-CoV-2 from four animal hosts, including domestic dog, domestic cat, mink and white-tailed deer, showed no or only minor differences from the human-derived reference, both in terms of phylogenetic trees and majority amino acids. It is more likely that they were infected with SARS-CoV-2 from humans. In previous studies, Hale VL et al. and Chandler JC et al. found that white-tailed deer can carry SARS-CoV-220,21. Palmer MV et al. also found that white-tailed deer can exhibit subclinical symptoms after nasal inoculation with SARS-CoV-2 and that humans can be infected through contact with white-tailed deer22. Studies in Poland and Hong Kong, China, found SARS-CoV-2 infection in domestic dogs and cats, but it was not clear whether it could be transmitted to humans15,23,24. American mink on fur farms in the Netherlands, Denmark, Poland and Utah, USA, have been found to have widespread infections, posing a significant risk of transmission to farm workers and other local wildlife, making them worthy of attention as potential intermediate hosts25,26,27,28. Additionally, the Spanish study has identified SARS-CoV-2 infection in two wild minks within self-sustaining populations29. A plausible explanation for the infection in these animals is that they were sporadically exposed to viruses present in wastewater30. This highlights the potential significance of an indirect transmission route, possibly through wastewater, as a source of infection that warrants thorough investigation. Due to a relatively independent host ecosystem and microecosystem, the evolutionary dynamics of these viruses tend to be different from those that persist and circulate in the human population, which can lead to the emergence of novel variants that are more adapted to humans18. Selective pressure (usually from the host immune system) plays the dominant role. Under positively selective pressure, in order to evade the immune response of the animal host and establish a persistent infection, the virus exhibits high genetic variation, making it possible for new variation signatures to occur31,32. Our study confirmed the presence of most positively selected sites within the S protein of viruses isolated from these hosts as well as their respective genera. This suggests that, over time, human-derived SARS-CoV-2 infecting and circulating in these animals may sooner or later evolve into novel variants that may be better adapted to humans. If re-introduced into humans through cross-species transmission, it is possible to trigger re-emerging pandemics. In terms of SARS-CoV-2 alone, viruses currently circulating in domestic dog, domestic cat, mink and white-tailed deer as well as their respective genera may be more dangerous, as these viruses are subject to continuous selection in their animal hosts, potentially leading to novel variants of SARS-CoV-2. Therefore, monitoring of SARS-CoV-2 carried by these sentinel animals should be emphasized to prevent the emergence of novel variants and back transmission to humans.

Viruses from the Manis and Rhinolophus genera showed significant differences from the human reference on the phylogenetic trees, suggesting that the possibility of direct transmission from them to humans and vice versa is not substantial. Previous and ongoing studies have shown that the beta-coronaviruses carried by bats and pangolins pose a potential threat to human public health, as they may evolve into new coronaviruses other than SARS-CoV-2 that can infect humans through continuous variation11,12,33. In order to monitor the possible emergence of new SARS-like-CoVs outbreaks in the future, emphasis should be placed on real-time investigation of host animals belonging to the genera Manis and Rhinolophus. For the same purpose, the genus Panthera (especially lions) is particularly worthy of close monitoring, as it not only has the most statistically significant differential majority of amino acids (except for Manis and Rhinolophus genera), but also has the most positively selected sites (except for Canis, Felis, Neovison and Odocoileus genera). Our study showed that all host-derived viruses, except lion, tended to cluster separately during the early phase and mix together afterward. However, the lion-derived sequences consistently formed a distinct cluster both early and late phases of the pandemic (Fig. 2A, D, E). It is not easy to determine whether the lion-derived virus originated from humans during the pandemic or had been circulating previously. In addition, the lion, which has the highest number of statistically significant differential amino acids and a high number of positively selected sites (just after domestic dog, domestic cat, mink and white-tailed deer), clustered close to the genera of Manis and Rhinolophus. We cautiously raise the question of whether the lion-derived viruses are of human-origin, or whether there is a relatively independent lineage of SARS-CoV-2 within lion that triggered the pandemic. A recent review described positive contact tracing studies confirming possible lion-to-human transmission34. Although the lion-transmitted viruses exhibit complexity and uncertainty in both origin and evolutionary trends, the number of positively selected sites also warrants attention to prevent the emergence of new strains of beta-coronaviruses that could be transmitted to humans.

Specific laboratory animals such as mice (Mus musculus), green monkeys, western gorillas (Gorilla gorilla) and snow leopards (Panthera uncia) also need to be monitored. Nonhuman primates are often used as medical research animals to create disease models. According to the World Organization for Animal Health (WOAH) database (https://www.woah.org/en/document/sars-cov-2-in-animals-situation-report-20/), both natural infections with SARS-CoV-2 and spillover events between humans and gorillas have been reported. Once the virus carried by nonhuman primates has mutated into a novel variant, the species barrier that must be crossed to infect humans is minimal.

SARS-CoV-2 appears to be capable of infecting several mammalian species. Detections of this virus in pets, zoo animals, wildlife and livestock have raised questions about zoonotic (animal-to-human) reinfection of humans. To date, however, the COVID-19 pandemic has revealed a global paucity of publicly available biological samples that are representative of space, time and taxonomic diversity. The shortage is particularly severe in biodiverse and low-income countries. Taxonomically, geographically, and temporally comprehensive surveillance in these countries may not be practical35,36, but to extrapolate animals from known sentinel host species to the genus, family, and even order of the taxonomic hierarchies for monitoring purposes may be triable. Our study recommends the inclusion of animals belonging to the genera of Canis, Felis, Neovison, Odocoileus, Panthera, Mustela, and Aonyx etc. as potential sentinel hosts for surveillance, especially the first five genera. In the host taxonomic hierarchy of the genus, SARS-CoV-2 derived from them has been detected more positively selected sites within the S protein.

Combining the results of amino acid polymorphism and positively selected sites, five sites (142, 501, 655, 681 and 950) in the S protein require special attention, one of which is located in the NTD (142), one in the RBD (501) and one in the furin protease cleavage site (681). The amino acids at these five sites may have a tendency to vary, which could lead to the development of a novel SARS-CoV-2 variant that is better adapted to humans. This is consistent with much research on the relationship between these sites and the infectious properties of SARS-CoV-237,38,39. In our study, for example, the amino acid residue at cleavage site 681 is differential in three taxonomic hierarchies: family (Circetidae), genera (Panthera, Mesocricetus) and species (lion, tiger, golden hamster); the residue at site 142 is differential in four taxonomic hierarchies: order (Primates), family (Circetidae), genera (Panthera, Mustela) and species (lion, golden hamster); the residue at site 950 is differential only in the Panthera genus and lion species; at site 501 is differential only in the ferret species. All of these sites are likely to be critical in determining host tropism40. Variations at these sites increase the binding affinity of the S protein to the ACE2 receptor or decrease its affinity to antibodies, leading to immune escape, making the mutant strains more transmissible and potentially increasing their host range41,42,43.

Our study highlights the need for a robust One Health-based investigation to monitor susceptible animal hosts. Since the emergence of the COVID-19 epidemic, normal human life and economic activities have been severely disrupted worldwide. It is important to regularly monitor the evolution of SARS-CoV-2 in both human and animal populations and to adopt an approach that sustainably balances and optimizes human, animal and ecosystem health to build a community of human health.

SARS-CoV-2 genomic data were obtained from two databases, the National Center for Biotechnology Information (NCBI, https://www.ncbi.nlm.nih.gov/) and the Global Initiative of Sharing All Influenza Data (GISAID) EpiCoV (https://gisaid.org/). Nonhuman mammalian viral genomes were downloaded according to host species, while human viral genomes were downloaded separately according to PANGO lineages, with only the earliest 10 genomes downloaded for each PANGO lineage.

The viral genomes were aligned using MAFFT 7.503 with the complete S gene of isolate Wuhan-Hu-1 (NC_045512) as a reference. The aligned genomic sequences were trimmed using MEGA 6.0 software, retaining only the S genes. Due to the large number of human-derived viral genomes, a special quality control procedure was implemented. Any genomic sequence with a total number of ‘n’ greater than 40 or containing more than three consecutive ‘n’ was considered to be of sub-optimal sequencing quality and was therefore excluded from subsequent analyses.

The principle of sequence inclusion is that if the number of sequences in a given taxonomic hierarchy is less than six, it is considered insufficient for basic sampling needs and is therefore not analysed in that hierarchy, but is retained and merged up to the higher level of the taxonomic hierarchies, and so on. The taxonomic hierarchies used in this study were species, genus, family and order, all belonging to the class Mammalia.

Phylogenetic trees were constructed using the neighbour-joining method with bootstrap analysis of 1,000 replicates in MEGA 6.0, using the p-distance nucleotide substitution model and selecting pairwise deletion for gaps data treatment.

For ease of presentation, no more than 20 of the earliest sequences from each species were retained to construct the overall phylogenetic tree. Sequences from the widespread genera Manis and Rhinolophus are quite different from those of human-origin, so additional phylogenetic analyses were performed for them.

To investigate potential SARS-like-CoVs (other than SARS-CoV-2) carried by these nonhuman mammals, phylogenetic analysis of the virus from each mammalian species was also performed separately according to time of collection (before and after 2020) and region (NTD and RBD and full-length S gene). Due to the large number of sequences from animal hosts after 2020, CD-HIT 4.8.1 Linux version was used with a threshold of 99.65% to exclude the redundancies.

The coding regions of human and nonhuman mammalian S sequences were translated into amino acids using the Megalign module of Lasergene software. The majority of amino acids at each site was counted in the taxonomic hierarchy levels of host species, genera, families and orders, and then compared one by one with that of the human-derived SARS-CoV-2. Chi-square tests were performed using SPSS 19.0 to determine whether there were statistically significant differences in the amino acid majority at each site.

The aligned S gene sequences were used to explore the selective pressure on the viruses in the taxonomic hierarchies of host species, genera, families and orders. The SLAC (Single-Likelihood Ancestor Counting) and FUBAR (Fast Unconstrained Bayesian Approximation) programs on the Datamonkey Web server (http://www.datamonkey.org/) were executed for this purpose44.

The methodological flow chart for this study is shown in the Supplementary Fig. S3.

Some or all data, models, or code generated or used during the study are available from the corresponding author by request.

WHO. COVID-19 Weekly Epidemiological Update. (2023).

Kadam, S. B., Sukhramani, G. S., Bishnoi, P., Pable, A. A. & Barvkar, V. T. SARS-CoV-2, the pandemic coronavirus: Molecular and structural insights. J. Basic. Microbiol. 61, 180–202. https://doi.org/10.1002/jobm.202000537 (2021).

Article PubMed PubMed Central Google Scholar

Wang, Q. et al. A unique protease cleavage site predicted in the spike protein of the Novel Pneumonia Coronavirus (2019-nCoV) potentially related to viral transmissibility. Virol. Sin. 35, 337–339. https://doi.org/10.1007/s12250-020-00212-7 (2020).

Article PubMed PubMed Central Google Scholar

Harvey, W. T. et al. SARS-CoV-2 variants, spike mutations and immune escape. Nat. Rev. Microbiol. 19, 409–424. https://doi.org/10.1038/s41579-021-00573-0 (2021).

Article PubMed PubMed Central Google Scholar

Xia, X. Domains and functions of spike protein in Sars-Cov-2 in the context of Vaccine Design. Viruses. 13 https://doi.org/10.3390/v13010109 (2021).

Zhang, J., Xiao, T., Cai, Y. & Chen, B. Structure of SARS-CoV-2 spike protein. Curr. Opin. Virol. 50, 173–182. https://doi.org/10.1016/j.coviro.2021.08.010 (2021).

Article PubMed PubMed Central Google Scholar

Chen, Y. et al. Broadly neutralizing antibodies to SARS-CoV-2 and other human coronaviruses. Nat. Rev. Immunol. 23, 189–199. https://doi.org/10.1038/s41577-022-00784-3 (2023).

Article PubMed Google Scholar

Xu, X. et al. Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission. Sci. China Life Sci. 63, 457–460. https://doi.org/10.1007/s11427-020-1637-5 (2020).

Article PubMed PubMed Central Google Scholar

Paraskevis, D. et al. Full-genome evolutionary analysis of the novel corona virus (2019-nCoV) rejects the hypothesis of emergence as a result of a recent recombination event. Infect. Genet. Evol. 79, 104212. https://doi.org/10.1016/j.meegid.2020.104212 (2020).

Article PubMed PubMed Central Google Scholar

Benvenuto, D. et al. The 2019-new coronavirus epidemic: evidence for virus evolution. J. Med. Virol. 92, 455–459. https://doi.org/10.1002/jmv.25688 (2020).

Article PubMed PubMed Central Google Scholar

Zhang, T., Wu, Q. & Zhang, Z. Probable pangolin origin of SARS-CoV-2 Associated with the COVID-19 outbreak. Curr. Biol. 30, 1346–1351e1342. https://doi.org/10.1016/j.cub.2020.03.022 (2020).

Article PubMed PubMed Central Google Scholar

Xiao, K. et al. Isolation of SARS-CoV-2-related coronavirus from Malayan pangolins. Nature. 583, 286–289. https://doi.org/10.1038/s41586-020-2313-x (2020).

Article ADS PubMed Google Scholar

Li, X. et al. Emergence of SARS-CoV-2 through recombination and strong purifying selection. bioRxiv. https://doi.org/10.1101/2020.03.20.000885 (2020).

Article PubMed PubMed Central Google Scholar

Schindell, B. G., Allardice, M., McBride, J. A. M., Dennehy, B. & Kindrachuk, J. SARS-CoV-2 and the Missing Link of Intermediate hosts in viral emergence - what we can learn from other Betacoronaviruses. Front. Virol. 2https://doi.org/10.3389/fviro.2022.875213 (2022).

Sit, T. H. C. et al. Infection of dogs with SARS-CoV-2. Nature. 586, 776–778. https://doi.org/10.1038/s41586-020-2334-5 (2020).

Article ADS PubMed PubMed Central Google Scholar

McAloose, D. et al. From people to Panthera: natural SARS-CoV-2 infection in Tigers and Lions at the Bronx Zoo. mBio. 11 https://doi.org/10.1128/mBio.02220-20 (2020).

Gaudreault, N. N. et al. SARS-CoV-2 infection, disease and transmission in domestic cats. Emerg. Microbes Infect. 9, 2322–2332. https://doi.org/10.1080/22221751.2020.1833687 (2020).

Article PubMed PubMed Central Google Scholar

McBride, D. S. et al. Accelerated evolution of SARS-CoV-2 in free-ranging white-tailed deer. Nat. Commun. 14, 5105. https://doi.org/10.1038/s41467-023-40706-y (2023).

Article ADS PubMed PubMed Central Google Scholar

Su, S. et al. Epidemiology, genetic recombination, and Pathogenesis of coronaviruses. Trends Microbiol. 24, 490–502. https://doi.org/10.1016/j.tim.2016.03.003 (2016).

Article PubMed PubMed Central Google Scholar

Hale, V. L. et al. SARS-CoV-2 infection in free-ranging white-tailed deer. Nature. 602, 481–. https://doi.org/10.1038/s41586-021-04353-x (2022).

Article ADS PubMed Google Scholar

Chandler, J. C. et al. SARS-CoV-2 exposure in wild white-tailed deer (Odocoileus virginianus). Proc. Natl. Acad. Sci. U S A. 118 https://doi.org/10.1073/pnas.2114828118 (2021).

Palmer, M. V. et al. Susceptibility of white-tailed deer (Odocoileus virginianus) to SARS-CoV-2. J. Virol. 95https://doi.org/10.1128/jvi.00083-21 (2021).

Bao, L. et al. Susceptibility and attenuated transmissibility of SARS-CoV-2 in domestic cats. J. Infect. Dis. 223, 1313–1321. https://doi.org/10.1093/infdis/jiab104 (2021).

Article PubMed Google Scholar

Sharun, K., Saied, A. A., Tiwari, R. & Dhama, K. SARS-CoV-2 infection in domestic and feral cats: current evidence and implications. Vet. Q. 41, 228–231. https://doi.org/10.1080/01652176.2021.1962576 (2021).

Article PubMed PubMed Central Google Scholar

Shriner, S. A. et al. SARS-CoV-2 exposure in escaped Mink, Utah, USA. Emerg. Infect. Dis. 27, 988–990. https://doi.org/10.3201/eid2703.204444 (2021).

Article PubMed PubMed Central Google Scholar

Khalid, M., Alshishani, A. & Al-Ebini, Y. Genome similarities between human-derived and mink-derived SARS-CoV-2 make Mink a potential Reservoir of the Virus. Vaccines (Basel). 10https://doi.org/10.3390/vaccines10081352 (2022).

Rabalski, L. et al. Severe Acute Respiratory Syndrome Coronavirus 2 in Farmed Mink (Neovison vison), Poland. Emerg. Infect. Dis. 27, 2333–2339. https://doi.org/10.3201/eid2709.210286 (2021).

Article PubMed PubMed Central Google Scholar

Hammer, A. S. et al. SARS-CoV-2 transmission between Mink (Neovison vison) and humans, Denmark. Emerg. Infect. Dis. 27, 547–551. https://doi.org/10.3201/eid2702.203794 (2021).

Article ADS PubMed PubMed Central Google Scholar

Aguiló-Gisbert, J. et al. First description of SARS-CoV-2 infection in two feral American Mink (Neovison vison) caught in the Wild. Animals. 11, 1422. https://doi.org/10.3390/ani11051422 (2021).

Article PubMed PubMed Central Google Scholar

Padilla-Blanco, M. et al. The Finding of the severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) in a wild Eurasian River Otter (Lutra lutra) highlights the need for viral surveillance in wild mustelids. Front. Veterinary Sci. 9 https://doi.org/10.3389/fvets.2022.826991 (2022).

Nunes, B. et al. Heterogeneous selective pressure acting on influenza B Victoria- and Yamagata-like hemagglutinins. J. Mol. Evol. 67, 427–435. https://doi.org/10.1007/s00239-008-9154-9 (2008).

Article ADS PubMed Google Scholar

Torresi, J., Johnson, D. & Wedemeyer, H. Progress in the development of preventive and therapeutic vaccines for hepatitis C virus. J. Hepatol. 54, 1273–1285. https://doi.org/10.1016/j.jhep.2010.09.040 (2011).

Article PubMed Google Scholar

Lau, S. K. P. et al. Severe acute respiratory syndrome coronavirus-like virus in Chinese horseshoe bats. Proceedings of the National Academy of Sciences 102, 14040–14045, doi: (2005). https://doi.org/10.1073/pnas.0506735102

Siegrist, A. A. et al. Probable transmission of SARS-CoV-2 from African Lion to Zoo employees, Indiana, USA, 2021. Emerg. Infect. Dis. 29, 1102–1108. https://doi.org/10.3201/eid2906.230150 (2023).

Article PubMed PubMed Central Google Scholar

Colella, J. P. et al. Leveraging natural history biorepositories as a global, decentralized, pathogen surveillance network. PLoS Pathog. 17, e1009583. https://doi.org/10.1371/journal.ppat.1009583 (2021).

Article PubMed PubMed Central Google Scholar

Goraichuk, I. V., Arefiev, V., Stegniy, B. T. & Gerilovych, A. P. Zoonotic and reverse zoonotic transmissibility of SARS-CoV-2. Virus Res. 302, 198473. https://doi.org/10.1016/j.virusres.2021.198473 (2021).

Article PubMed Google Scholar

Liu, Y. et al. Delta spike P681R mutation enhances SARS-CoV-2 fitness over alpha variant. Cell. Rep. 39https://doi.org/10.1016/j.celrep.2022.110829 (2022).

Jeong, B. S. et al. Structural basis for the broad and potent cross-reactivity of an N501Y-centric antibody against sarbecoviruses. Front. Immunol. 13, 1049867. https://doi.org/10.3389/fimmu.2022.1049867 (2022).

Article PubMed PubMed Central Google Scholar

Liu, S., Huynh, T., Stauft, C. B., Wang, T. T. & Luan, B. Structure-function analysis of resistance to Bamlanivimab by SARS-CoV-2 variants Kappa, Delta, and Lambda. J. Chem. Inf. Model. 61, 5133–5140. https://doi.org/10.1021/acs.jcim.1c01058 (2021).

Article PubMed Google Scholar

Tan, C. C. S. et al. Transmission of SARS-CoV-2 from humans to animals and potential host adaptation. Nat. Commun. 13, 2988. https://doi.org/10.1038/s41467-022-30698-6 (2022).

Article ADS PubMed PubMed Central Google Scholar

Wang, X. et al. Evaluating the effect of SARS-CoV-2 spike mutations with a linear doubly robust learner. Front. Cell. Infect. Microbiol. 13, 1161445. https://doi.org/10.3389/fcimb.2023.1161445 (2023).

Article PubMed PubMed Central Google Scholar

Chen, J., Gao, K., Wang, R. & Wei, G. W. Revealing the threat of emerging SARS-CoV-2 mutations to antibody therapies. J. Mol. Biol. 433, 167155. https://doi.org/10.1016/j.jmb.2021.167155 (2021).

Article PubMed PubMed Central Google Scholar

Kurhade, C. et al. Low neutralization of SARS-CoV-2 Omicron BA.2.75.2, BQ.1.1 and XBB.1 by parental mRNA vaccine or a BA.5 bivalent booster. Nat. Med. 29, 344–347. https://doi.org/10.1038/s41591-022-02162-x (2023).

Article PubMed Google Scholar

Weaver, S. et al. Datamonkey 2.0: a modern web application for characterizing selective and other evolutionary processes. Mol. Biol. Evol. 35, 773–777. https://doi.org/10.1093/molbev/msx335 (2018).

Article PubMed PubMed Central Google Scholar

Download references

This research was funded by the Shanghai New Three-year Action Plan for Public Health (2023-2025, Grant No. GWVI-11.1-03), the National Natural Science Foundation of China (Grants 81872673) and the Three-Year Action Plan of Shanghai Public Health System Construction-Key Discipline Construction (2020-2022, Grant No. GWV-10.1-XK03). The funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report.

Yanjiao Li, Jingjing Hu, Jingjing Hou and Shuiping Lu contributed equally to this work.

Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200433, China

Yanjiao Li, Jingjing Hu, Shuiping Lu, Yuxi Wang, Weijie Chen, Yue Pan, Qingwu Jiang, Weibing Wang & Chenglong Xiong

Key Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai, 200433, China

Yanjiao Li, Jingjing Hu, Shuiping Lu, Yuxi Wang, Weijie Chen, Yue Pan, Qingwu Jiang, Weibing Wang & Chenglong Xiong

Department of Pulmonary and Critical Care Medicine, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065, China

Jingjing Hou

Division of Emergency Management, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, 200336, China

Jiasheng Xiong

Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, 43400, Malaysia

Zhong Sun & Karuppiah Thilakavathy

Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China

Yi Feng

You can also search for this author in PubMed Google Scholar

Y. L., S. L., J. X. and C. X. wrote the first draft of the paper; Y. L., J. Hou, Y. W. and W. C. performed the literature search; J. Hu, J. X., Z. S. and Y. P. performed the data processing; K. T., Y. F., Q. J., W. W. and C. X. performed the systems review. C.X. and W. W. supervised the study. All authors made substantial revisions and critical review, and all authors have seen and approved the final version.

Correspondence to Weibing Wang or Chenglong Xiong.

The authors declare no competing interests.

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Below is the link to the electronic supplementary material.

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Reprints and permissions

Li, Y., Hu, J., Hou, J. et al. Study on sentinel hosts for surveillance of future COVID-19-like outbreaks. Sci Rep 14, 24595 (2024). https://doi.org/10.1038/s41598-024-76506-7

Download citation

Received: 12 April 2024

Accepted: 14 October 2024

Published: 19 October 2024

DOI: https://doi.org/10.1038/s41598-024-76506-7

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

Vitamin B12 treatment Rozebalamin approved for ALS in Japan

Trial analysis shows vitamin D supplementation doesn't cut cardiac risk

News

Study on sentinel hosts for surveillance of future COVID-19-like outbreaks | Scientific Reports