Robust antiviral activity of commonly prescribed antidepressants against emerging coronaviruses: in vitro and in silico drug repurposing studies

Abstract

During the current coronavirus disease 2019 (COVID-19) pandemic, symptoms of depression are commonly documented among both symptomatic and asymptomatic quarantined COVID-19 patients. Despite that many of the FDA-approved drugs have been showed anti-SARS-CoV-2 activity in vitro and remarkable efficacy against COVID-19 in clinical trials, no pharmaceutical products have yet been declared to be fully effective for treating COVID-19. Antidepressants comprise five major drug classes for the treatment of depression, neuralgia, migraine prophylaxis, and eating disorders which are frequently reported symptoms in COVID-19 patients. Herein, the efficacy of eight frequently prescribed FDA-approved antidepressants on the inhibition of both SARS-CoV-2 and MERS-CoV was assessed. Additionally, the in vitro anti-SARS-CoV-2 and anti-MERS-CoV activities were evaluated. Furthermore, molecular docking studies have been performed for these drugs against the spike (S) and main protease (Mpro) pockets of both SARS-CoV-2 and MERS-CoV. Results showed that Amitriptyline, Imipramine, Paroxetine, and Sertraline had potential anti-viral activities. Our findings suggested that the aforementioned drugs deserve more in vitro and in vivo studies targeting COVID-19 especially for those patients suffering from depression.

Design, Synthesis, Biological Evaluation, and Molecular Dynamics Studies of Novel Lapatinib Derivatives

“…Then, to prepare the designed compounds ( 6a – l ) for the docking processes, they were sketched using ChemDraw Professional program, introduced individually into the working window of the MOE, 3D hydrogenated, and energy minimized as previously described [ 49 , 50 ]. The prepared derivatives ( 6a – l ) were inserted into two different databases besides the co-crystallized inhibitor (AQ4 or 03P) for EGFR and HER2 docking processes, respectively.…”

Investigating the possible mechanisms of pirfenidone to be targeted as a promising anti-inflammatory, anti-fibrotic, anti-oxidant, anti-apoptotic, anti-tumor, and/or anti-SARS-CoV-2

“…Coronavirus illness (COVID-19) is a global pandemic that has caused problems for public health and the economy [132] , [133] , [134] , [135] . In patients with COVID-19, cytokine storms, multiorgan failure, and especially acute respiratory distress syndrome (ARDS) are the major causes of mortality and morbidity [136] , [137] , [138] .…”

In vitroand computational investigations of novel synthetic carboxamide-linked pyridopyrrolopyrimidines with potent activity as SARS-CoV-2-MProinhibitors

“…This functional importance, together with the absence of a closely related analogous target in humans, made the SARS-CoV-2 main protease M pro an interesting target for the design of antiviral agents. 5,8,9 Consequently, many attempts have been adopted to develop M pro inhibitor-based antiviral medication. As a result, a number of antiviral agents with prominent activity against SARS-CoV-2 were discovered.…”

“…As a result, a number of antiviral agents with prominent activity against SARS-CoV-2 were discovered. These include boceprevir (8) and GC-376 (9) which were veried as inhibitors of M pro through binding to its catalytic active site. 10 Computational methods play an important role in the design of novel M pro antagonistic drugs.…”