Potential SARS-CoV-2 interactions with proteins involved in trophoblast functions - An in-silico study.

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.

Is pregnancy an immunological contributor to severe or controlled COVID-19 disease?

Since its emergence in Wuhan as a novel coronavirus disease, it has taken only a few months since January 2020 for it to be recognized as a widespread COVID-19 pandemic which has contributed to global health devastation. As pointed out by health experts, it is a once in a century pandemic of our times. Clinical observations so far indicate that the older population and immune compromised individuals, particularly in African American and Hispanic/Latino communities, are at much higher risk for infection with this novel coronavirus. In this regard, pregnancy offers an altered immunity scenario which may allow severe COVID-19 disease. The literature is so far highly conflicting on this issue. This review will offer a conceptual basis for severe or controlled disease and address trepidations for pregnant women associated with COVID-19 pandemic, particularly in the comparative context of clinical consequences of other coronaviruses such as SARS and MERS. We will highlight the possible consequences of COVID-19 on the general health of pregnant women as well as its possible effects at the maternal-fetal interface. For the placenta-related pathology, we will focus our discussion on the temporal expression of ACE2 throughout gestation for possible propagation of SARS-CoV-2 in the placenta in infected women and ensuing consequences.