Version 1
: Received: 26 March 2024 / Approved: 27 March 2024 / Online: 28 March 2024 (08:38:26 CET)
How to cite:
Azad, A. Network Medicine-Based Approach Reveals Cyclosporine and Selinexor Drug Combination as an Effective Therapy against SARS-COV-2. Preprints2024, 2024031708. https://doi.org/10.20944/preprints202403.1708.v1
Azad, A. Network Medicine-Based Approach Reveals Cyclosporine and Selinexor Drug Combination as an Effective Therapy against SARS-COV-2. Preprints 2024, 2024031708. https://doi.org/10.20944/preprints202403.1708.v1
Azad, A. Network Medicine-Based Approach Reveals Cyclosporine and Selinexor Drug Combination as an Effective Therapy against SARS-COV-2. Preprints2024, 2024031708. https://doi.org/10.20944/preprints202403.1708.v1
APA Style
Azad, A. (2024). Network Medicine-Based Approach Reveals Cyclosporine and Selinexor Drug Combination as an Effective Therapy against SARS-COV-2. Preprints. https://doi.org/10.20944/preprints202403.1708.v1
Chicago/Turabian Style
Azad, A. 2024 "Network Medicine-Based Approach Reveals Cyclosporine and Selinexor Drug Combination as an Effective Therapy against SARS-COV-2" Preprints. https://doi.org/10.20944/preprints202403.1708.v1
Abstract
The proliferation of SARS-COV-2 through enhanced viral replication and its subsequent triggering of cytokine storm, are some of the hallmark phenotypes in severe COVID-19 patient cases. Cyclosporine, an immunosuppressant drug and Selinexor, an inhibitor of nuclear transporter protein, both have been successfully demonstrated to be effective against SARS-COV-2 infection by targeting those functions individually. However, the highly multifactorial pathology of SARS-COV-2 infection hinders any mono-therapeutic strategy to become an optimal option. In this study, we assess the potential efficacy of the Cyclosporine-Selinexor combination on an integrated interactome by adopting a network-medicine-based repositioning technique, where disease proximity, functional proximity and their topological separation are evaluated, followed by a robust statistical significance test. Results have shown that both drug target modules are highly proximal to the SARS-COV-2 disease modules in terms of network topology and functional associations, in a statistically significant manner, individually. Functional enrichment of both drug modules and SARS-COV-2 infected modules has shown that two drugs target the functions related to viral replication and cytokine storm during infection. Moreover, a high degree of network separation been those two drug target modules has been observed, revealing ``complementary exposure`` patterns, rendering this drug combination as an effective one against SARS-COV-2 infection. We hope that our results will encourage researchers to further investigate the potency of Cyclosporine and Selinexor combination in vivo or in vitro, and ultimately lead that up to clinical trials to treat SARS-COV-2 patients.
Keywords
Cyclosporine; Selinexor; Drug Combination; Network Medicine; SARS-COV-2; Functional Enrichment; Drug Target
Subject
Computer Science and Mathematics, Mathematical and Computational Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
