Is Fostamatinib a possible drug for COVID-19? – A computational study

Abstract

COVID-19 has turned out to be a global pandemic within a very short period since its first origin in China in December2019. With the gradual increase in the mortality rate all over the world, there is an urgent need for an effectual drug. Though no clinically approved vaccine or drug is available until now but scientists are trying hard to identify potential antivirals to this new coronavirus. Several drugs like hydroxychloroquine, remdesivir, azithromycin etc. are put under evaluation in more than 300 clinical trials for the treatment of COVID-19. Few of them already show encouraging results. The main agent of disease progression of COVID-19 is SARS-CoV2/nCoV, which is believed to have ~89% genetic resemblance with SARSCoV, a coronavirus responsible for the massive outbreak in 2003. With this hypothesis, a recently developed in silico Human-nCoV network and potential COVID-19 spreader proteins, have been derived from the Human-SARS-CoV protein interactions using SIS model and fuzzy thresholding, followed by a potential FDA drugs target based validation. We then perform a two-way analysis to identify the potential drug targets of COVID-19. In the first analysis, we identify the complete list of FDA drugs for the 37 level 1 and 4948 level 2 spreader proteins in this network followed by the application of a consensus strategy. In the second analysis, the same consensus strategy is applied but on a curated overlapping set of key genes identified from COVID-19 symptoms, risk factors and clinical outcome. The applied consensus strategy in both the analysis reveals that Fostamatinib, a FDA approved drug, has the highest drug consensus score both in level 1 and level 2. Further analysis reveals that Fostamatinib also targets CYP3A4, a level 2 spreader protein and the most common target formost of the potential COVID-19 drugs. A subsequent docking study also reveals that Fostamatinib has also the highest docking score with respect to 6LU7, the crystal structure of COVID-19 main protease in complex with an inhibitor N3, in comparison to other potential drugs like hydroxychloroquine, remdesivir, favipiravir and darunavir. Our computational study suggests that Fostamatinib may also be considered as one of the potential candidates for further clinical trials in pursuit to counter the spread of COVID-19.

Integrated network analysis reveals new genes suggesting COVID-19 chronic effects and treatment

“…Fostamatinib is currently used to treat autoimmune diseases and thrombocytopenia, but it has recently been proposed for COVID-19 disease treatment by Saha et al. [ 86 ]. Similar to fostamatinib, we retrieved several drugs targeting the coagulation cascade, such as kappadione, a vitamin K analogue, and menadione, used in hypoprothrombinemia treatment.…”

A systems-based method to repurpose marketed therapeutics for antiviral use: a SARS-CoV-2 case study

“…Among the top predicted SARS-CoV-2–specific drug repurposing candidates were fostamatinib, glutathione, and valproic acid. Fostamatinib, artenimol, and bosutinib were identified in other bioinformatic studies as a potential treatment option to target human proteins associated with COVID-19 ( 36 , 37 ). Furthermore, fostamatinib is used to treat chronic immune thrombocytopenia, a condition associated with severe COVID-19 ( 38 ).…”

Detection of spreader nodes in human-SARS-CoV protein-protein interaction network

“…Spreadability index is applied along with a unique fuzzy protein-protein interaction model to form SARS-CoV2-human PPIN in our other research work (Saha et al, 2020a). The formed PPIN is also compared (Saha et al, 2020b) with that of SARS-CoV2-Human PPIN generated in the work of Gordon et al (Gordon et al, 2020). Henceforth, study and analysis of drug repurposing of COVID-19 are also implemented in the subsequent research work (Saha et al, 2020b).…”

“…The formed PPIN is also compared (Saha et al, 2020b) with that of SARS-CoV2-Human PPIN generated in the work of Gordon et al (Gordon et al, 2020). Henceforth, study and analysis of drug repurposing of COVID-19 are also implemented in the subsequent research work (Saha et al, 2020b). Thus, it explores a new direction in identifying essential drugs/vaccines for SARS-CoV2.…”