Are losartan and imatinib effective against SARS-CoV2 pathogenesis? A pathophysiologic-based in silico study
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ORIGINAL RESEARCH
Are losartan and imatinib effective against SARS‑CoV2 pathogenesis? A pathophysiologic‑based in silico study Reza Nejat1 · Ahmad Shahir Sadr2,3,4,5 Received: 24 July 2020 / Accepted: 4 November 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Proposing a theory about the pathophysiology of cytokine storm in COVID19, we were to find the potential drugs to treat this disease and to find any effect of these drugs on the virus infectivity through an in silico study. COVID-19-induced ARDS is linked to a cytokine storm phenomenon not explainable solely by the virus infectivity. Knowing that ACE2, the hydrolyzing enzyme of AngII and SARS-CoV2 receptor, downregulates when the virus enters the host cells, we hypothesize that hyperacute AngII upregulation is the eliciting factor of this ARDS. We were to validate this theory through reviewing previous studies to figure out the role of overzealous activation of AT1R in ARDS. According to this theory losartan may attenuate ARDS in this disease. Imatinib, has previously been elucidated to be promising in modulating lung inflammatory reactions and virus infectivity in SARS and MERS. We did an in silico study to uncover any probable other unconsidered inhibitory effects of losartan and imatinib against SARS-CoV2 pathogenesis. Reviewing the literature, we could find that over-activation of AT1R could explain precisely the mechanism of cytokine storm in COVID19. Our in silico study revealed that losartan and imatinib could probably: (1) decline SARS-CoV2 affinity to ACE2. (2) inhibit the main protease and furin, (3) disturb papain-like protease and p38MAPK functions. Our reviewing on renin-angiotensin system showed that overzealous activation of AT1R by hyper-acute excess of AngII due to acute downregulation of ACE2 by SARS-CoV2 explains precisely the mechanism of cytokine storm in COVID-19. Besides, based on our in silico study we concluded that losartan and imatinib are promising in COVID19. Keywords SARS-CoV2 · Losartan · Imatinib · Cytokine storm · Papain-like protease · Main protease
Introduction
Reza Nejat and Ahmad Shahir Sadr contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s40203-020-00058-7) contains supplementary material, which is available to authorized users.
Since December 2019, a viral disease called COVID-19 has hunted thousands of people savagely all around the world and the death toll increases in a skyrocketing manner every day. It was elucidated that a coronavirus named SARSCoV2 caused the disease eventually named as COVID-19 (Chan et al. 2020; Viruses 2020). Coronaviruses are classified into the order Nidovirales, the suborder Coronavirinae,
* Reza Nejat [email protected]
3
Department of Computer Science, Faculty of Mathematical Sciences, Shahid Beheshti University, Tehran, Iran
Ahmad Shahir Sadr [email protected]
4
Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Behesh
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