In Silico Screening of the Phenolic Compound Oleuropein and Its Hydrolysis Product 3-Hydroxytyrosol Against Certain Structural and Non-Structural Proteins of SARS-CoV- 2
Erman Salih Istıflı · Türk Tarım ve Doğa Bilimleri Dergisi · 2021
The novel corona virus has infected nearly 163 million people globally as of May 2021 and caused death of more than 3.3 million patients. Despite intense efforts, however, a small molecule with full therapeutic potential has not been developed in the treatment of SARS-CoV-2. The aim of this study was to investigate the inhibitory potentials of oleuropein and its hydrolysis product 3-hydroxytyrosol against spike glycoprotein, papain-like protease, main protease and RNA-dependent RNA polymerase of SARS-CoV-2 using molecular modelling simulations. Compared to 3-hydroxytyrosol, oleuropein showed stronger binding affinity to all targets in docking, and its affinity to Mpro (-7.0 kcal mol-1) and RdRp (-8.0 kcal mol-1) was quite high. Despite the Mpro-oleuropein complex, the RdRp-oleuropein complex showed a highly stable binding in 15-ns molecular dynamics based on root-mean-square-deviation (0.14 - 0.32 nm) and hydrogen bond numbers (6.85). The intracellular targets of oleuropein covered various proteases (17%), enzymes (16%), family A G protein-coupled receptors (11%), kinases (10%) and other cytosolic proteins (10%), however, probabilistic analysis showed that oleuropein was unlikely (p = 0 - 0.22) to bind these targets. ADMET profile showed that, with few exceptions, oleuropein has the physicochemistry that should be present in a drug molecule. In conclusion, oleuropein binds tightly to the active site of RdRp and could inhibit this enzyme. Oleuropein may be used alone or in combination with replicase inhibitors such as remdesivir or favipiravir in the treatment of COVID-19. Additional in vitro binding assays and in vivo efficacy studies are needed to prove our findings.