International Journal of Novel Trends in Pharmaceutical Sciences

REVIEW ARTICLE Keerthi Chadam Venkatesulu et al., Int. J Nov. Tren. Pharm. Sci. 2020; 10(3): 67-70 INTERNATIONAL JOURNAL OF NOVEL TRENDS IN PHARMACEUTICAL SCIENCES Published by ScienzTech Publication Journal Home Page: www.scienztech.org/ijntps Role of estrogen in the management of COVID – 19 in females Keerthi Chadam Venkatesulu* , Shaik Habeeb Jan, Harika Sree Gaddam Department of Pharmacy Practice, Seven Hills College of Pharmacy, Vekataramapuram, Thanapalle, Tirupathi-517561, Andhra Pradesh, India Article History: Received on: 10 Sep 2020 Revised on: 01 Oct 2020 Accepted on: 20 Oct 2020 Published on: 30 Nov 2020 Volume: 10 Issue: 3 Keywords: Estrogen, Hormonal therapy, COVID19, Corona impact on females ∗ ABSTRACT With the increase, the spread of COVID-19 its effect can be seen on health care systems seek innovative treatment ways as the need of the hour. The suspected leading cause of COVID-19 is due to the response to in lammations and the cytokine storm, which majorly damages the lung tissue. The difference in response to the vaccine can be seen due to different sex. Moreover, age-related decrease in sex steroid hormones like Estrogen as well as testosterone can promote pro-in lammatory raise in older individuals which in turn increases the risk of COVID-19 related adverse outcomes. Such sex hormones have the capacity of mitigating in lammatory response and can also provide promising therapeutic bene its for patients suffering from COVID-19. Moreover, over above the effects of on any ERS, these drugs showed useful ancillary properties. Most showed to highlight broader roles in mitigating viral replication by the ER-independent mechanisms as mentioned. Data simpliies ER modulation an apt pharmacological approach for restricting storm and thus prevents the in lammation due to COVID-19. Mainly the application of or tissue-selective estrogen complex can provide a pharmacological response. Such treatment options can be fruitful for both sexes in the early phase of such disease condition to prevent further progression of the disease to severe forms. Corresponding Author Name: Keerthi Chadam Venkatesulu Phone: 8523086231 Email: kirthichandrika.333@gmail.com eISSN: 2277-2782 DOI: https://doi.org/10.26452/ijntps.v10i3.1355 Production and Hosted by ScienzTech.org © 2020 | All rights reserved. INTRODUCTION (SARS-CoV-2) is causing COVID-19 pandemic, which has already infected more than 8 million people and killed more than 550 000 globally [1, 2]. The search for an appropriate therapy is ongoing but is in wait to get success [3]. Thus we should look outside the box and consider the biological reasons as in why women are less effected from COVID-19 in compar- ison to men [4]. The suspected primary cause of COVID-19 is the in lammatory response and the cytokine storm, which majorly damages the lung tissue [5]. The difference in response to the vaccine can be seen due to different sex [6]. Moreover, age-related decrease in such sex steroid hormones, mainly estrogen and testosterone can promote pro-in lammatory raise in older individuals which in turn increases the chance of COVID-19 related adverse outcomes [7]. It is found that sex hormones hold the capacity of mitigating in lammatory response and can also provide better therapeutic bene its for patients suffering from COVID-19 [2]. COVID – 19 in males Vs females Male as well as females show prominent differences instead of several infective diseases which are caused by several viral pathogens [8]. Even though data reveals that COVID-19 has almost the same numbers of countable cases between men © ScienzTech Publication | International Journal of Novel Trends in Pharmaceutical Sciences 67 Keerthi Chadam Venkatesulu et al., Int. J Nov. Tren. Pharm. Sci. 2020; 10(3): 67-70 and women, however signi icant sex differences in terms of death rate and even in terms of vulnerability to Covid-19 is being observed. Recent data reveals that more men are dying than women, potentially it can be because of sex-based immunological differences [9, 10]. One more possible explanation can be the role of estrogens. Viral infections are found to vary between men and women in terms of prevalence, intensity and various pathogenic mechanism [11, 12]. Estrogen regulation of COVID-19 through ACE – ef icient in females Estrogen controls cytokines storm by initiating suppression of IL-1β and IL-6 production, as a result of which it reduces the risk of any acute lungs in lammation in women. Estrogen might also play a signi icant role in lowering the exhaustion of T cells caused by cytokines storm. However, the protective mechanism by Estrogen in reducing ER stress is not reported and established yet as studies estrogen show it’s a crucial role by reducing ER stress, caused by the infection [23]. ACKNOWLEDGEMENTS SARS-CoV-2 is dependent on angiotensin-converting enzyme 2 (ACE2) for the cell entry, which in turn engages serine protease transmembrane protease serine 2 (TMPRSS2) for priming viral spike protein. Thus both ACE2 & TMPRSS2 are important for SARSCoV-2 to cause this infection. It is found thatE2 treated NHBE cells expresses lower levels of ACE2 mRNA in comparison with treated controls. E2 SARS-CoV2 ace/angiotensin-II receptor modula- driven downregulation of ACE2 expression is helpful in this regard as the ef iciency of ACE2 usage by tion and estrogen therapy Virus SARS-Cov has infected and destroyed the lives SARS-CoV is found to be an essential determinant in of many human being starting from the end of terms of viral replication as well as disease severity. 2019 and the beginning of 2020, which is contin- Estrogen receptor modulators a possible “adjuued [13]. Even though science and technology are vant drugs” most advanced, most of the countries are still strug- Endogenous estrogens show a protective effect, gling to overcome this pandemic [14]. Virus SARS- which is highlighted by drugs of the class SERMs. CoV-2 have RNA as its single-stranded genetic mate- These drugs show agonist as well as antagonist rial [15]. Human coronavirus comes under the cat- modulatory response of the ER subtypes, which in egory of second genera corona viridae family [16]. turn shows in lammatory responses. The outer membrane of this virus is made of protein A preclinical study explained the need of sex horwhich is known as surface protein [17]. mones in a particular single-gender – highlightInitially, it was believed that this particular infec- ing the vulnerability of SARS-CoV virus where both tious disease would transmit from animal to human, types of mice were infected with SARS-CoV. Male but later it was clear that it spreads via human to mice were found to be more susceptible to SARS-CoV human transmission [18, 19]. Coronavirus spread infection compared to female mice [24]. this infection by inserting its genetic material, i.e. Moreover, over above the effects of SERMs on any single-stranded RNA genome into the host cell and ERS, these drugs showed useful ancillary properties. immediately which starts its replication and thus Most SERMs showed to highlight broader roles in produces ER stress in mainly three ways which are mitigating viral replication by the ER-independent a) Forming double-membrane vesical (DMV), mechanisms as mentioned [25]. b) Glycosylating viral proteins CONCLUSION c) Depleting ER membrane lipids. However, estrogen hormone can lower the burden Data simpli ies ER modulation an apt pharmacologiof ER stress, and it does by activating unfolded pro- cal approach for restricting cytokine storm and thus tein response (UPR) [20]. Once ER stress is expe- prevents the in lammation due to COVID-19. Mainly rienced, then to counteract estrogen hormone binds the application of SERMs or tissue-selective estroto its receptor ERα which is present in the cytoplasm gen complex can provide a favourable pharmacologas a result of this binding, rapid activation of phos- ical response. Such treatment options can be fruitful pholipase C enzyme happens which cleaves its sub- for both sexes in the early phase of such disease constrate PIP2 into DAG (diacylglycerol) andIP3 (inosi- dition to prevent further progression of the disease to severe forms. tol triphosphate) [21, 22]. 68 The authors are thankful to all who have extended their constant support for the completion of the work. Funding Support The authors declare that they have no funding support for this study. © ScienzTech Publication | International Journal of Novel Trends in Pharmaceutical Sciences Keerthi Chadam Venkatesulu et al., Int. J Nov. Tren. Pharm. 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