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Potential SARS-CoV-2 interactions with proteins involved in trophoblast functions - An in-silico study.
Placenta. 2021 01 01; 103:141-151.P

Abstract

BACKGROUND

Though a large number of pregnant females have been affected by COVID-19, there is a dearth of information on the effects of SARS-CoV-2 infection on trophoblast function. We explored in silico, the potential interactions between SARS-CoV-2 proteins and proteins involved in the key functions of placenta.

METHODS

Human proteins interacting with SARS-CoV-2 proteins were identified by Gordon et al. (2020). Genes that are upregulated in trophoblast sub-types and stages were obtained by gene-expression data from NCBI-GEO and by text-mining. Genes altered in pathological states like pre-eclampsia and gestational diabetes mellitus were also identified. Genes crucial in placental functions thus identified were compared to the SARS-CoV-2 interactome for overlaps. Proteins recurring across multiple study scenarios were analyzed using text mining and network analysis for their biological functions.

RESULTS

The entry receptors for SARS-CoV-2 - ACE2 and TMPRSS2 are expressed in placenta. Other proteins that interact with SARS-CoV-2 like LOX, Fibulins-2 and 5, NUP98, GDF15, RBX1, CUL3, HMOX1, PLAT, MFGE8, and MRPs are vital in placental functions like trophoblast invasion and migration, syncytium formation, differentiation, and implantation. TLE3, expressed across first trimester placental tissues and cell lines, is involved in formation of placental vasculature, and is important in SARS-CoV (2003) budding and exit from the cells by COPI vesicles.

CONCLUSION

SARS-CoV-2 can potentially interact with proteins having crucial roles in the placental function. Whether these potential interactions identified in silico have effects on trophoblast functions in biological settings needs to be addressed by further in vitro and clinical studies.

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Authors+Show Affiliations

Seethy AA
Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
Singh S
Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
Mukherjee I
Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India; Amity Institute of Biotechnology, Amity University, Noida, India.
Pethusamy K
Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
Purkayastha K
Department of Paediatrics, All India Institute of Medical Sciences, New Delhi, India.
Sharma JB
Department of Obstetrics and Gynaecology, All India Institute of Medical Sciences, New Delhi, India.
Sharma RS
Indian Council of Medical Research, New Delhi, India.
Dhar R
Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India. Electronic address: rubydhar@gmail.com.
Karmakar S
Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India. Electronic address: subhradip.k@aiims.edu.

MeSH

COVID-19Computational BiologyComputer SimulationDatasets as TopicFemaleHEK293 CellsHumansPlacentaPregnancyPregnancy Complications, InfectiousPregnancy ProteinsPregnancy Trimester, FirstProtein BindingProtein Interaction MapsProteomicsSARS-CoV-2TrophoblastsUp-Regulation

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33126048

Citation

Seethy, Ashikh A., et al. "Potential SARS-CoV-2 Interactions With Proteins Involved in Trophoblast Functions - an In-silico Study." Placenta, vol. 103, 2021, pp. 141-151.
Seethy AA, Singh S, Mukherjee I, et al. Potential SARS-CoV-2 interactions with proteins involved in trophoblast functions - An in-silico study. Placenta. 2021;103:141-151.
Seethy, A. A., Singh, S., Mukherjee, I., Pethusamy, K., Purkayastha, K., Sharma, J. B., Sharma, R. S., Dhar, R., & Karmakar, S. (2021). Potential SARS-CoV-2 interactions with proteins involved in trophoblast functions - An in-silico study. Placenta, 103, 141-151. https://doi.org/10.1016/j.placenta.2020.10.027
Seethy AA, et al. Potential SARS-CoV-2 Interactions With Proteins Involved in Trophoblast Functions - an In-silico Study. Placenta. 2021 01 1;103:141-151. PubMed PMID: 33126048.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Potential SARS-CoV-2 interactions with proteins involved in trophoblast functions - An in-silico study. AU - Seethy,Ashikh A, AU - Singh,Sunil, AU - Mukherjee,Indrani, AU - Pethusamy,Karthikeyan, AU - Purkayastha,Kakali, AU - Sharma,Jai Bhagwan, AU - Sharma,Radhey S, AU - Dhar,Ruby, AU - Karmakar,Subhradip, Y1 - 2020/10/22/ PY - 2020/06/03/received PY - 2020/09/29/revised PY - 2020/10/22/accepted PY - 2020/10/31/pubmed PY - 2021/3/12/medline PY - 2020/10/30/entrez KW - COVID-19 KW - Placenta KW - Pregnancy KW - Protein-protein interaction KW - SARS-CoV-2 KW - Trophoblast SP - 141 EP - 151 JF - Placenta JO - Placenta VL - 103 N2 - BACKGROUND: Though a large number of pregnant females have been affected by COVID-19, there is a dearth of information on the effects of SARS-CoV-2 infection on trophoblast function. We explored in silico, the potential interactions between SARS-CoV-2 proteins and proteins involved in the key functions of placenta. METHODS: Human proteins interacting with SARS-CoV-2 proteins were identified by Gordon et al. (2020). Genes that are upregulated in trophoblast sub-types and stages were obtained by gene-expression data from NCBI-GEO and by text-mining. Genes altered in pathological states like pre-eclampsia and gestational diabetes mellitus were also identified. Genes crucial in placental functions thus identified were compared to the SARS-CoV-2 interactome for overlaps. Proteins recurring across multiple study scenarios were analyzed using text mining and network analysis for their biological functions. RESULTS: The entry receptors for SARS-CoV-2 - ACE2 and TMPRSS2 are expressed in placenta. Other proteins that interact with SARS-CoV-2 like LOX, Fibulins-2 and 5, NUP98, GDF15, RBX1, CUL3, HMOX1, PLAT, MFGE8, and MRPs are vital in placental functions like trophoblast invasion and migration, syncytium formation, differentiation, and implantation. TLE3, expressed across first trimester placental tissues and cell lines, is involved in formation of placental vasculature, and is important in SARS-CoV (2003) budding and exit from the cells by COPI vesicles. CONCLUSION: SARS-CoV-2 can potentially interact with proteins having crucial roles in the placental function. Whether these potential interactions identified in silico have effects on trophoblast functions in biological settings needs to be addressed by further in vitro and clinical studies. SN - 1532-3102 UR - https://www.unboundmedicine.com/medline/citation/33126048/Potential_SARS_CoV_2_interactions_with_proteins_involved_in_trophoblast_functions___An_in_silico_study_ DB - PRIME DP - Unbound Medicine ER -