Abstract
In the current report, we studied the possible inhibitors of COVID-19 from bioactive constituents of Centaurea jacea using a threefold approach consisting of quantum chemical, molecular docking and molecular dynamic techniques. Centaurea jacea is a perennial herb often used in folk medicines of dermatological complaints and fever. Moreover, anticancer, antioxidant, antibacterial and antiviral properties of its bioactive compounds are also reported. The Mpro (Main proteases) was docked with different compounds of Centaurea jacea through molecular docking. All the studied compounds including apigenin, axillarin, Centaureidin, Cirsiliol, Eupatorin and Isokaempferide, show suitable binding affinities to the binding site of SARS-CoV-2 main protease with their binding energies -6.7 kcal/mol, -7.4 kcal/mol, -7.0 kcal/mol, -5.8 kcal/mol, -6.2 kcal/mol and -6.8 kcal/mol, respectively. Among all studied compounds, axillarin was found to have maximum inhibitor efficiency followed by Centaureidin, Isokaempferide, Apigenin, Eupatorin and Cirsiliol. Our results suggested that axillarin binds with the most crucial catalytic residues CYS145 and HIS41 of the Mpro, moreover axillarin shows 5 hydrogen bond interactions and 5 hydrophobic interactions with various residues of Mpro. Furthermore, the molecular dynamic calculations over 60 ns (6×106 femtosecond) time scale also shown significant insights into the binding effects of axillarin with Mpro of SARS-CoV-2 by imitating protein like aqueous environment. From molecular dynamic calculations, the RMSD and RMSF computations indicate the stability and dynamics of the best docked complex in aqueous environment. The ADME properties and toxicity prediction analysis of axillarin also recommended it as safe drug candidate. Further, in vivo and in vitro investigations are essential to ensure the anti SARS-CoV-2 activity of all bioactive compounds particularly axillarin to encourage preventive use of Centaurea jacea against COVID-19 infections.
Highlights
Viral infections are continued to emerge and symbolize a major problem to public health
Inhibition constant obtained from the binding energies of Mpro in complex with Apigenin, Axillarin, Centaureidin, Cirsiliol, Eupatorin and Isokaempferide were 11.77 μM, 3.59 μM, 7.08 μM, 54.09 μM, 27.46 μM and 9.94 μM respectively see table 1
We have successfully performed molecular docking and molecular dynamic studies to explore the potential of different compounds as potential inhibitor for COVID-19 Mpro from Centaurea jacea
Summary
Viral infections are continued to emerge and symbolize a major problem to public health. In last 20 years, numerous viral epidemics such as the SARS-CoV (severe acute respiratory syndrome coronavirus) in 2002 to 2003, H1N1 pandemic in 2009 and MERS-CoV (Middle East respiratory syndrome coronavirus) was first discovered in Saudi Arabia in 2012, have been reported (Perlman and Netland, 2009; Chan et al, 2013). Previous studies have described that CoVs (coronaviruses) are an etiologic agent of various infections especially respiratory and digestive disorders in mammals, reptiles, avian species and humans (Malik et al, 2020). In the last weeks of 2019, a viral infection COVID-19 caused by a novel virus named as SARSCoV-2 (severe acute respiratory syndrome–coronavirus 2), a new strain of CoVs has been reported in Wuhan, China and spread rapidly throughout the whole world (Wu et al, 2020). SARS-Cov-2 has been identified as an enveloped, non-segmented RNA virus with 29.5kb genome (Adem et al, 2020). Genome sequencing of SARS-CoV-2 showed that SARS-CoV-2 is 96.2% identical to a bat CoV and the RNA genome of SARS-CoV-2 is 79.5% identical with the RNA genome of SARS-CoV (Lu et al, 2020; Wu et al, 2020; Zhou et al, 2020)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
