Working Paper Article Version 2 This version is not peer-reviewed

Predicting and Repurposing of Drug and Drug Like Compounds for Inhibition of the Covid-19 and Its Cytokine Storm by Computational Methods

Version 1 : Received: 30 March 2020 / Approved: 31 March 2020 / Online: 31 March 2020 (10:23:10 CEST)
Version 2 : Received: 22 April 2020 / Approved: 23 April 2020 / Online: 23 April 2020 (14:56:22 CEST)

How to cite: Sallari Jazzi, A.; Mahnam, K.; Hossein Hejazi, S.; Damavandi, M.S.; Sadeghi, P.; Zeinalian, M.; Tabesh, F.; Mirbod, S.M.; Khanahmad, H. Predicting and Repurposing of Drug and Drug Like Compounds for Inhibition of the Covid-19 and Its Cytokine Storm by Computational Methods. Preprints 2020, 2020030457 Sallari Jazzi, A.; Mahnam, K.; Hossein Hejazi, S.; Damavandi, M.S.; Sadeghi, P.; Zeinalian, M.; Tabesh, F.; Mirbod, S.M.; Khanahmad, H. Predicting and Repurposing of Drug and Drug Like Compounds for Inhibition of the Covid-19 and Its Cytokine Storm by Computational Methods. Preprints 2020, 2020030457

Abstract

Background: The SARS-CoV-2 virus is a new highly pathogen virus that can suppress cell immune response (Poly ADPR process, and interferon releasing in infected cell) by viral macrodomain and create fatal pneumonia. Cytokine storm phenomenon which can create consequence of SARS COV-2 by increase of the performance of human TRPM2, is a dangerous condition for human and its body organ such as kidney, heart, and liver. it seems like prevention of beginning of these events is necessary. Material and methods: in this study drug and drug like database was used for inhibition of the viral macrodomain and human TRPM2 that can initiate of the viral cell cycle infection and human cytokine storm respectively. Ligand base drug designed, pharmacophore modeling, docking and molecular dynamic simulation was performed Results: among up to billion compounds, 20 compounds were screened by infinisee program. Then 7 compounds were selected by pharmacophore modeling. between 7 compounds, 5 compound was removed because of high similarity to ADPR and possibility of toxic effect for human RNA and DNA polymerase. One compound was losartan and selected for docking and molecular dynamic simulation. Conclusion: losartan earned a proper dock score and binding affinity to create the complexes with TRPM2 and macrodomain. Molecular dynamic simulation has shown losartan had an adequate binding free energy for human trpm2 and viral macrodomain. The inhibitory effect of losartan on these protein has shown and it could interfere in several points (PARP, PARG- macrodomain and TRPM2) and decreases oxidative stress, apoptosis, cytokine storm in COVID-19.

Subject Areas

Viral Macrodomain; COVID-19; TRPM2; losartan; Bioinformatics

Comments (1)

Comment 1
Received: 23 April 2020
Commenter: Hossein Khanahmad
Commenter's Conflict of Interests: Author
Comment: Title and abstract changed
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