TABLE 1.
The potential intermediate hosts for SARS-CoV-2.
| Species | Analytic method | Supported evidence or opposed reason | References |
| Pangolin | Gene Sequence Analysis and Comparison | Malayan pangolins contain sequences strongly similar to SARS-CoV-2 | Xiao et al., 2020 |
| High-throughput Sequencing and phylogenetic analysis | Pangolin-nCoV belongs to two sub-lineages of SARS-CoV-2 related coronaviruses | Lam et al., 2020 | |
| Molecular and phylogenetic analyze the assembled complete genome of pangolin-nCoV | Pangolin-nCoV have the highly conserved S genes and structure of RBD protein to SARS-CoV-2 | Liu P. et al., 2020 | |
| Gene sequence analysis of coronavirus genomes reconstructed from viral metagenomic datasets of hosts and SARS-CoV-2 | High sequence similarity in the RBM between SARS-CoV-2 and a coronavirus genome from datasets of pangolin | Wong et al., 2020 | |
| Systematic comparison and analysis to predict the interaction between the RBD and the ACE2 | Regarding the similarity of the key amino acids of interaction between RBD and ACE2 to humans, the pangolin is closer than the bat | Liu Z. et al., 2020 | |
| Molecular evolution and phylogenetic analysis of SARS-CoV-2 and hosts ACE2 protein | The evolutionary divergence between pangolin ACE2 and hACE2 is lower than that between bat ACE2 and hACE2 | Lopes et al., 2020 | |
| The phylogenetic tree based on Hausdorff distance and Center distance between SARS-CoV-2 strains and host-nCoV groups | The pangolin-nCoV is closely related to the SARS-CoV-2 group based on the genome divergences | Dong et al., 2020 | |
| Phylogenetic, split network, transmission network, and comparative analyses of the genomes | The pangolin-nCoV from the two pangolin samples did not have the PRRA insertion, which is crucial in viral invasion | Li X. et al., 2020 | |
| Virus infectivity studies using HEK293T cells expressing ACE2 from 11 species of animals | Pangolin ACE2 could mediate SARS-CoV-2 entry | Tang et al., 2020 | |
| Pseudotyping particles of Spike mimics particle entry and quantitative cell-cell fusion assay | Pangolin sustained higher levels of entry than was seen with an equivalent hACE2 construct | Conceicao et al., 2020 | |
| Mink | Compare the infectivity patterns by deep learning algorithm of VHP | Mink coronavirus have the closest infectious patterns to SARS-CoV-2 | Guo et al., 2020 |
| Genetic and epidemiological sleuthing | The SARS-CoV-2 outbreak in mink farms is introduced by humans, and infected minks can transmit the virus to human and other animals via viral dust or droplets | Oreshkova et al., 2020 | |
| Turtle | Systematic comparison and analysis to predict the interaction between the RBD and ACE2 | Regarding the similarity of the key amino acids of interaction between RBD and ACE2 to humans, the turtle is closer than the bat | Liu Z. et al., 2020 |
| Analyze the affinity to S protein of the 20 key residues in ACE2 | Oppose: Nearly half of the 20 key residues in ACE2 from turtles were abolished | Luan J. et al., 2020a | |
| Snake | Relative synonymous codon usage (RSCU) comparison and analysis | Snake shared the lowest RSCU distance to SARS-CoV-2 | Ji et al., 2020 |
| Analyze the affinity to S protein of the 20 key residues in ACE2 | Oppose: Nearly half of the 20 key residues in ACE2 from snakes were abolished | Luan J. et al., 2020a | |
| Reperform the RSCU comparison and analysis conducted by Ji et al. (2020) | Oppose: RSCU is not specific enough to identify the intermediate host | Zhang C. et al., 2020 | |
| Ferrets | Establish a ferret model of SARS-CoV-2 infection and transmission | SARS-CoV-2 is effectively transmitted to naïve ferrets by direct contact and leads acute bronchiolitis | Kim et al., 2020 |
| Intranasally inoculated SARS-CoV-2 to domestic animals | Ferrets have high susceptibility to SARS-CoV-2 | Shi et al., 2020 | |
| Pseudotyping particles of Spike mimics particle entry and quantitative cell-cell fusion assay | Ferret ACE2 is not used efficiently by SARS-CoV-2 for entry | Conceicao et al., 2020 | |
| Bovidae (yak) | Analyze the affinity to S protein of the 20 key residues in ACE2 | The majority of key residues in ACE2 are identical to hACE2 protein | Luan J. et al., 2020a |
| Phylogenetic tree analysis and structural models’ comparison | A yak betacoronavirus strain has spike glycoproteins structure models closest to SARS-CoV-2 | Dabravolski and Kavalionak, 2020 | |
| Dogs | Pseudotyping particles of Spike mimics particle entry and quantitative cell-cell fusion assay | Dog sustained higher levels of entry than was seen with an equivalent hACE2 construct | Conceicao et al., 2020 |
| Intranasally inoculated SARS-CoV-2 to domestic animals | Oppose: Dogs have little susceptibility to SARS-CoV-2 | Shi et al., 2020 | |
| Investigate the level of ACE2 expression in different organs | Oppose: Higher mRNA levels in organs such as kidney and heart, while low mRNA levels in respiratory tract | Zhai et al., 2020 | |
| Use single-cell technique to screen of ACE2 and TMPRSS2(SARS-CoV-2 target cell) in different organs of animals | Oppose: Co-expression of ACE2 and TMPRSS2 is absent in poultry lung cells and rare in dog lung cells | Chen D. S. et al., 2020 | |
| Virus infectivity studies using HEK293T cells expressing ACE2 from 11 species of animals | Dog ACE2 could mediate SARS-CoV-2 entry | Tang et al., 2020 | |
| Cats | Intranasally inoculated SARS-CoV-2 to domestic animals | Cats have high susceptibility to SARS-CoV-2 | Shi et al., 2020 |
| Phylogenetic clustering and sequence alignment to evaluate the receptor-utilizing capability of ACE2 | Cat ACE2 have the receptor-utilizing capability of SARS-CoV-2 | Qiu et al., 2020 | |
| Use expressed RBD proteins to perform surface staining of cells transfected with expression plasmids of ACE2 orthologs | Cats support the efficient entry of SARS-CoV-2, SARS-CoV, and Bat-nCoV RaTG13 | Li Y. J. et al., 2020 | |
| Intranasally inoculated SARS-CoV-2 or close contact with infected cat | Cats are subclinical infection and shed virus for no more than 5 days | Bosco-Lauth et al., 2020 | |
| Pseudotyping particles of Spike mimics particle entry and quantitative cell–cell fusion assay | Cat sustained higher levels of entry than was seen with an equivalent hACE2 construct | Conceicao et al., 2020 | |
| Use single-cell technique to screen of ACE2 and TMPRSS2(SARS-CoV-2 target cell) in different organs of animals | Cats have the highest proportion of SARS-CoV-2 target cell, and those cells were widely distributed among digestive system, respiratory system and urinatory system | Chen D. S. et al., 2020 | |
| Virus infectivity studies using HEK293T cells expressing ACE2 from 11 species of animals | Cat ACE2 could mediate SARS-CoV-2 entry | Tang et al., 2020 | |
| Swine (pigs) | Phylogenetic clustering and sequence alignment to evaluate the receptor-utilizing capability of ACE2 | Swine ACE2 have the receptor-utilizing capability of SARS-CoV-2 | Qiu et al., 2020 |
| Use expressed RBD proteins to perform surface staining of cells transfected with expression plasmids of ACE2 orthologs | Pigs support the efficient entry of SARS-CoV-2, SARS-CoV, and Bat-nCoV RaTG13 | Li Y. J. et al., 2020 | |
| Use single-cell technique to screen of ACE2 and TMPRSS2 (SARS-CoV-2 target cell) in different organs of animals | Pig have a variety of cell types co-expressing SARS-ACE2 and TMPRSS2 | Chen D. S. et al., 2020 | |
| Virus infectivity studies using HEK293T cells expressing ACE2 from 11 species of animals | Pig ACE2 could mediate SARS-CoV-2 entry | Tang et al., 2020 | |
| Intranasally inoculated SARS-CoV-2 to domestic animals | Oppose: Pigs have little susceptibility to SARS-CoV-2 | Shi et al., 2020 | |
| Investigate the level of ACE2 expression in different organs | Oppose: Higher mRNA levels in organs such as kidney and heart, while low mRNA levels in respiratory tract | Zhai et al., 2020 |