Superiority of cilostazol among antiplatelet FDA‐approved drugs against COVID 19 M^pro and spike protein: Drug repurposing approach

Abstract

Coronavirus disease 2019 (COVID 19) was first identified in Wuhan, China near the end of 2019. To date, COVID‐19 had spread to almost 235 countries and territories due to its highly infectious nature. Moreover, there is no vaccine or Food and Drug Administration (FDA)‐approved drug. More time is needed to establish one of them. Consequently, the drug repurposing approach seems to be the most attractive and quick solution to accommodate this crisis. In this regard, we performed molecular docking‐based virtual screening of antiplatelet FDA‐approved drugs on the key two viral target proteins: main protease (Mpro) and spike glycoprotein (S) as potential inhibitor candidates for COVID‐19. In the present study, 15 antiplatelet FDA‐approved drugs were investigated against the concerned targets using the Molecular Docking Server. Our study revealed that only cilostazol has the most favorable binding interaction on Mpro (PDB ID: 6LU7) and cilostazol, iloprost, epoprostenol, prasugrel, and icosapent ethyl have a higher binding affinity on spike glycoprotein (S) (PDB ID: 6VYB) compared with recent anti‐CoVID‐19. Therefore, cilostazol is a promising FDA drug against COVID‐19 by inhibiting both Mpro and S protein. The insights gained in this study may be useful for quick approach against COVID‐19 in the future.

Tioconazole and Chloroquine Act Synergistically to Combat Doxorubicin-Induced Toxicity via Inactivation of PI3K/AKT/mTOR Signaling Mediated ROS-Dependent Apoptosis and Autophagic Flux Inhibition in MCF-7 Breast Cancer Cells

“…PubChem's database uses the 3D chemical structures of Doxorubicin, Chloroquine, and Tioconazole. Auto Dock 4 was used for docking accounts; then the Molecular Docking Server (https://www.dockingserver.com accessed on 7 July 2019) was used [14], Protein structures and the selected drugs were prepared as previously described [77].…”

Potential antiviral properties of antiplatelet agents against SARS-CoV-2 infection: an in silico perspective

“…The authors' recently published docking study suggests the possibility of antiplatelet drugs against COVID-19 [ 24 ]. To prove these drugs' effectiveness, we include molecular dynamics simulation for the SARS-CoV-2 protein targets M pro and the spike protein for 100 ns (see the supplementary figure S1).…”

“…The structure of the ligands (FDA- approved Antiplatelets) are retrieved from the PubChem database and prepared for the docking study [ 24 , 25 ]. Additionally, the SARS-CoV-2 M pro and spike protein structures are retrieved from the Protein Data Bank (PDB ID: 6Y84 and 6YLA, respectively).…”

“…So, drug repurposing has been launched as an inspiring approach, as recommended by WHO [ 23 ]. Our group recently revealed the promising role of antiplatelet FDA-approved drugs in the treatment of COVID-19 by inhibiting main protease (M pro ) and spike glycoprotein (S) [ 24 ].…”

Nonsteroidal anti-inflammatory drugs and glucocorticoids in COVID-19

“…In silico screening suggests that an antagonist of PGE 2 receptor 4 (EPR4), grapiprant, interferes with the interaction between SARS-CoV-2 and cell surface binding of an immunoglobin protein by locking the substrate binding domain in a closed conformation ( Zhang et al, 2021 ). In addition, a docking-based virtual screening of antiplatelet FDA-approved drugs revealed that iloprost and epoprostenol, two stable prostacyclin analogs, have promising binding interactions with S-protein ( Abosheasha and El-Gowily, 2021 ). However, the impact of these interactions on viral entry or replication has yet to be elucidated.…”