This recombinant ACE2 protein is a mammalian cell-expressed, C-terminal hFc-tagged form of Paguma larvata (masked palm civet) ACE2, comprising the extracellular domain (amino acids 18-740). It demonstrates high purity (>90% determined by SDS-PAGE and SEC-HPLC) and low endotoxin levels (<1.0 EU/μg, LAL method), ensuring compatibility with sensitive cellular and enzymatic assays. Functionally validated, this recombinant ACE2 protein binds immobilized SARS-CoV S-RBD (CSB-MP348663HQE) with high affinity (EC50: 5.056–7.559 ng/mL in ELISA) and exhibits enzymatic activity via cleavage of the fluorogenic substrate Mca-Ala-Pro-Lys(Dnp)-OH (Km: 22.84 μM). The hFc tag enhances stability and facilitates detection/purification. Provided as a lyophilized powder, this protein is ideal for studying ACE2-mediated viral entry mechanisms (e.g., SARS-CoV interactions) and physiological roles in peptide metabolism. Mammalian expression ensures proper post-translational modifications, closely mimicking native protein behavior for reliable in vitro and in vivo applications.
The ACE2 protein from the Paguma larvata has been implicated in the host interactions of multiple coronaviruses, particularly as an intermediate host in the transmission pathways from bats to humans for SARS-CoV. The ACE2 receptor is critical as it serves as the entry point for these viruses into host cells. Molecular studies indicate that differences in ACE2 sequences across species can significantly affect their binding affinities to the spike proteins of SARS-CoV and SARS-CoV-2 [1][2][3]. Specifically, Paguma larvata ACE2 shows notable sequence alterations compared to human ACE2, including several key amino acid changes that could influence its interaction strength with the virus [1][4].
Research has demonstrated that the ACE2 receptor from Paguma larvata is capable of facilitating infection by SARS-CoV-2 due to a binding affinity that is sufficiently strong to allow viral entry [2][4]. This finding is supported by computational models that assessed the binding characteristics of the Paguma larvata ACE2 and compared them across various species, including both domestic and wild animals [5][4]. Importantly, studies indicate that the interaction energy scores for binding between the SARS-CoV-2 spike protein and the Paguma larvata ACE2 suggest substantial susceptibility to the virus, similar to other known susceptible species [6][7].
Furthermore, the palm civet's role as an intermediate host was notably observed during the early outbreaks of SARS-CoV, wherein it was discovered that genetic variants of the ACE2 receptor in civets played a significant role in the transmission dynamics of the virus from bats to humans [8][9]. It is also important to note that Paguma larvata has been the subject of extensive genomic analysis that revealed critical insights into its ACE2 sequence and subsequent implications for zoonotic transmissions. This species has been implicated as a critical link for earlier SARS-CoV spillover events and, more recently, in studies examining potential spillover risks for SARS-CoV-2 [10][11]. Continued research into animal ACE2 variants, particularly in civets, is essential for understanding the complexities of interspecies viral transmission [12][13].
References:
[1] X. Zhai, J. Sun, et al. Comparison of severe acute respiratory syndrome coronavirus 2 spike protein binding to ace2 receptors from human, pets, farm animals, and putative intermediate hosts. Journal of Virology, vol. 94, no. 15, 2020. https://doi.org/10.1128/jvi.00831-20
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[3] Y. Yang, M. Zheng, et al. Analysis of intermediate hosts and susceptible animals of sars-cov-2 by computational methods. Zoonoses, vol. 1, no. 1, 2021. https://doi.org/10.15212/zoonoses-2021-0010
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[7] J. Luan, Y. Lu, X. Jin, & L. Zhang. Spike protein recognition of mammalian ace2 predicts the host range and an optimized ace2 for sars-cov-2 infection. Biochemical and Biophysical Research Communications, vol. 526, no. 1, p. 165-169, 2020. https://doi.org/10.1016/j.bbrc.2020.03.047
[8] C. Baruah, P. Devi, & D. Sharma. Sequence analysis and structure prediction of sars‐cov‐2 accessory proteins 9b and orf14: evolutionary analysis indicates close relatedness to bat coronavirus. Biomed Research International, vol. 2020, no. 1, 2020. https://doi.org/10.1155/2020/7234961
[9] A. Camacho-Ortíz. A year after the start of covid-19. Revista Medicina Universitaria, vol. 23, no. 1, 2021. https://doi.org/10.24875/rmu.m21000056
[10] H. Mou, B. Quinlan, et al. Mutations derived from horseshoe bat ace2 orthologs enhance ace2-fc neutralization of sars-cov-2. Plos Pathogens, vol. 17, no. 4, p. e1009501, 2021. https://doi.org/10.1371/journal.ppat.1009501
[11] C. Devaux, L. Pinault, I. Osman, & D. Raoult. Can ace2 receptor polymorphism predicts species susceptibility to sars-cov-2? 2020. https://doi.org/10.21203/rs.3.rs-25753/v1
[12] C. Wu, M. Zheng, et al. In silico analysis of intermediate hosts and susceptible animals of sars-cov-2. 2020. https://doi.org/10.26434/chemrxiv.12057996.v1
[13] Z. Tan, K. Yong, & J. Shu. Predicting potential sars-cov-2 spillover and spillback in animals, Journal of Microbiology Immunology and Infection. vol. 57, no. 2, p. 225-237, 2024. https://doi.org/10.1016/j.jmii.2024.01.002
