Expression map of entry receptors and infectivity factors for pan-coronaviruses in preimplantation and implantation stage human embryos

Colaco, S.; Chhabria, K.; Singh, D.; Bhide, A.; Singh, N.; Singh, A.; Husein, A.; Mishra, A.; Sharma, R.; Ashary, N.; Modi, D.

PURPOSE: To predict if developing human embryos are permissive to multiple coronaviruses. METHOD: We analyzed publicly available single-cell RNA-seq datasets of human embryos for the known canonical and non-canonical receptors and spike protein cleavage enzymes for multiple coronaviruses like SARS-CoV, SARS-CoV-2, MERS-CoV, hCoV-229E, and hCoV-NL63. We also analyzed the expression of host genes involved in viral replication, host proteins involved in viral endosomal sorting complexes required for transport (ESCRT), genes of host proteins that physically interact with proteins of SARS-CoV-2, and the host genes essential for coronavirus infectivity. RESULTS: Of the known receptors of SARS viruses, ACE2, BSG, GOLGA7, and ZDHHC5 were expressed in different proportions in the zygote, 4-cell, 8-cell, morula, and blastocysts including the trophectoderm. The MERS-CoV receptor, DPP4, and hCoV-229E receptor, ANPEP, were expressed mainly from the compact morula to the blastocyst stages. Transcripts of the MERS-CoV alternate receptor LGALS1 were detected in most cells at all stages of development. TMPRSS2 transcripts were detected in the epiblast, primitive endoderm, and trophectoderm, while transcripts of the endosomal proteases CTSL, CTSB, and FURIN were expressed in most cells at all stages of development. ACE2 and TMPRSS2 were co-expressed in a proportion of epiblast and trophectoderm cells. The embryonic cells expressed genes involved in ESCRT, viral replication, SARS-CoV-2 interactions, and coronavirus infectivity. The ACE2 and TMPRSS2 co-expressing cells were enriched in genes associated with lipid metabolism, lysosome, peroxisome, and oxidative phosphorylation pathways. CONCLUSION: Preimplantation and implantation stage human embryos could be permissive to multiple hCoVs. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10815-021-02192-3.