Title:Virtual Screening Attributes Male Biased COVID-19 Mortality to Predicted Antiviral Activity of Female Sex Hormones
Volume: 18
Issue: 9
Author(s): Galal Yahya, Basem Mansour *, Kristina Keuper , Moataz Shaldam and Ahmed M. El-Baz
Affiliation:
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa 11152,Egypt
Keywords:
COVID-19, molecular docking, sex hormones, corticosteroids, ACE2 receptors, X- chromosome.
Abstract:
Background: Coronavirus disease-19 (COVID-19) is a newly emerged pandemic leading to a
state of international alert and leaving millions of infections and thousands of deaths all over the world.
Analysis of statistics and epidemiological data for the pandemic outcome pinpointed a puzzling influence
of human sex on the heterogeneous outcome of COVID-19, where hospital admissions and mortality were
higher among males than females. Two theories explained the observed male-biased COVID-19 mortality
based on either dosage of immunoregulatory genes coded in X- chromosomes, or on the abundance of the
angiotensin-converting enzyme two (ACE2) receptors in males than females.
Objective: In our study, we propose a third scenario through virtual screening of direct antiviral effects of
sex hormones.
Materials and Methods: Updated screening statistics from 47 countries displaying sex-disaggregated data
on COVID-19 were employed and visualized in the form of heatmaps depicting sex difference effects on
statistics of cases and deaths. Molecular docking and binding simulations of investigated sex steroids
against COVID-19 specific proteins were investigated.
Results: Analysis of COVID-19 sex-disaggregated data confirmed that male-biased mortality and
computer-aided docking found unexpected female sex hormones biased binding against key targets
implicated in the life cycle of COVID-19 compared to the male sex hormone testosterone. Other
investigated steroids showed promising docking scores, while the male sex hormone exhibited the lowest
affinity.
Conclusion: Female sex hormones virtually exhibit direct anti-COVID-19 effect, the proposed antiviral
effect of sex hormones should be considered to explain the outcomes of mortality. Moreover, the
fluctuation of sex hormones influences sex and personal derived-differential response to COVID-19
infection.
