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The impact of calcitriol and estradiol on the SARS-CoV-2 biological activity: a molecular modeling approach

Mansouri et al., Scientific Reports, doi:10.1038/s41598-022-04778-y
Jan 2022  
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In Silico study predicting that calcitriol and estradiol disrupt the interaction between the SARS-CoV-2 spike protein and ACE2. Authors note that calcitriol may be more effective in the presence of estradiol.
Mansouri et al., 13 Jan 2022, peer-reviewed, 5 authors.
In Silico studies are an important part of preclinical research, however results may be very different in vivo.
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The impact of calcitriol and estradiol on the SARS-CoV-2 biological activity: a molecular modeling approach
Alireza Mansouri, Rasoul Kowsar, Mostafa Zakariazadeh, Hassan Hakimi, Akio Miyamoto
Scientific Reports, doi:10.1038/s41598-022-04778-y
The novel coronavirus disease (COVID-19) is currently a big concern around the world. Recent reports show that the disease severity and mortality of COVID-19 infected patients may vary from gender to gender with a very high risk of death for seniors. In addition, some steroid structures have been reported to affect coronavirus, SARS-CoV-2, function and activity. The entry of SARS-CoV-2 into host cells depends on the binding of coronavirus spike protein to angiotensin converting enzyme-2 (ACE2). Viral main protease is essential for the replication of SARS-CoV-2. It was hypothesized that steroid molecules (e.g., estradiol, progesterone, testosterone, dexamethasone, hydrocortisone, prednisone and calcitriol) could occupy the active site of the protease and could alter the interaction of spike protein with ACE2. Computational data showed that estradiol interacted more strongly with the main protease active site. In the presence of calcitriol, the binding energy of the spike protein to ACE2 was increased, and transferring Apo to Locked S conformer of spike trimer was facilitated. Together, the interaction between spike protein and ACE2 can be disrupted by calcitriol. Potential use of estradiol and calcitriol to reduce virus invasion and replication needs clinical investigation. The novel coronavirus disease (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first recognized in the Hubei Province of China in December 2019 and has been reported as a very widespread disease with people-to-people transmission. Clinical evidence suggests that women are more resilient than men in terms of COVID-19 [1] [2] [3] [4] [5] . In the previous study, the critical factors involved in increasing the mortality and severity of COVID-19 in patients were investigated and higher disease severity and mortality were found in male patients 2 . It has been reported that 12.8% of 86 men died and 75.6% recovered, while 7.3% of 82 females died and 86.6% recovered 6 . In addition, the reports showed a relatively low risk of incidence in children but a very high risk of death in seniors 7 . Elderly patients diagnosed with COVID-19 aged 60 or older 8 had higher clinical signs, higher severity and longer periods of illness 9 . Sex steroid hormones are the primary cause of female and male differences. Testosterone (T) known as the predominant sex steroid hormone in males plays an essential role in sexual and reproductive development. In women, the predominant sex steroid hormones progesterone (P4) and estradiol (E2) are produced by ovaries. With respect to the menstrual cycle, the concentration of E2 reaches the highest level just before ovulation (during the follicular or proliferative phase) and then decreases shortly afterwards (during the luteal or secretory phase). P4 is released at peak level during the luteal phase, and then drops before the next menstrual period. Decreases in menopausal-associated ovarian hormones have been..
Author contributions Conceptualization: R.K., A.M.; Funding acquisition: R.K., A.M.; Investigation: Al.M., R.K., M.Z.; Methodology: Al.M., R.K., M.Z.; Software and Visualization: Al.M., M.Z.; Supervision: A.M., R.K.; Validation: Al.M., R.K., H.H., M.Z.; Writing-original draft: Al.M., R.K., M.Z., H.H.; Writing-review and editing: Al.M., R.K., M.Z., H.H., A.M. Competing interests The authors declare no competing interests. Additional information Supplementary Information The online version contains supplementary material available at https:// doi. org/ 10. 1038/ s41598-022-04778-y. Correspondence and requests for materials should be addressed to R.K. or A.M. Reprints and permissions information is available at Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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