Paradigm of Well-Orchestrated Pharmacokinetic Properties of Curcuminoids Relative to Conventional Drugs for the Inactivation of SARS-CoV-2 Receptors: An In Silico Approach
Akhileshwar Kumar Srivastava, Divya ; Singh, Priya ; Yadav, Monika ; Singh, Sandeep Kumar Singh, Ajay Kumar
Stresses, doi:10.3390/stresses3030043
To cure SARS-CoV-2 infection, the repurposing of conventional antiviral drugs is currently advocated by researchers, though their action is not very effective. The present study, based on in silico methods, was intended to increase the therapeutic potential of conventional drugs: hydroxychloroquine (HCQ), favipiravir (FAV), and remdesivir (REM) by using curcuminoids like curcumin (CUR), bisdemethoxycurcumin (BDMC), and demethoxycurcumin (DMC) as adjunct drugs against SARS-CoV-2 receptor proteins, namely main protease (Mpro) and the S1 receptor-binding domain (RBD). The curcuminoids exhibited similar pharmacokinetic properties to the conventional drugs. The webserver (ANCHOR) predicted greater protein stability for both receptors with a disordered score (<0.5). The molecular docking study showed that the binding energy was highest (-27.47 kcal/mol) for BDMC toward Mpro receptors, while the binding energy of CUR (-20.47 kcal/mol) and DMC (-20.58 kcal/mol) was lower than that of HCQ (-24.58 kcal/mol), FAV (-22.87 kcal/mol), and REM (-23.48 kcal/mol). In the case of S1-RBD, CUR had the highest binding energy (-38.84 kcal/mol) and the lowest was in FAV (-23.77 kcal/mol), whereas HCQ (-35.87 kcal/mol) and REM (-38.44 kcal/mol) had greater binding energy than BDMC (-28.07 kcal/mol) and DMC (-30.29 kcal/mol). Hence, this study envisages that these curcuminoids could be employed in combination therapy with conventional drugs to disrupt the stability of SARS-CoV-2 receptor proteins.
formation. Each result from FireDock provided a rank and scores based on the energy function. About 3.5 s was spent per candidate solution, which offers large-scale flexible refinement and the scoring of docking compounds to be performed. For the imaging of interactive molecules (antiviral drugs and curcuminoids) with SARS-CoV-2 receptors, a visualizer software, Discovery Studio 4.5 Client, was employed.
Conclusions Various promising antiviral drugs against COVID-19 are being examined, although there have not yet been satisfactory outcomes. This study has focused on exploring the main causes of these drugs' ineffectiveness against the COVID-19 disease. Hence, the two receptor proteins, Mpro and S1-RBD, of SARS-CoV-2 were considered as targets for developing new drugs. The physicochemical properties (ADMET, BOILED-Egg construction, and target class) exhibited by curcuminoids (CUR, BDMC, and DMC) were similar to those of antiviral drugs such as HCQ, FAV, and REM. Rat acute toxicity LD50 of all the compounds was found to be in the low ranges between 2.1259 and 2.7169 mol/kg, indicating that curcuminoids can be investigated further by comparing them with conventional antiviral drugs. The protein disordered outcomes from ANCHOR gained scores of less than 0.5 for residues of Mpro and S1-RBD, indicating that these protein receptors have highly packed residues. Thus, it is relatively difficult to disturb the integrity of such viral proteins by employing a single drug. The binding..
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'currently advocated by researchers, though their action is not very effective. The present '
'study, based on in silico methods, was intended to increase the therapeutic potential of '
'conventional drugs: hydroxychloroquine (HCQ), favipiravir (FAV), and remdesivir (REM) by '
'using curcuminoids like curcumin (CUR), bisdemethoxycurcumin (BDMC), and demethoxycurcumin '
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'the S1 receptor-binding domain (RBD). The curcuminoids exhibited similar pharmacokinetic '
'properties to the conventional drugs. The webserver (ANCHOR) predicted greater protein '
'stability for both receptors with a disordered score (<0.5). The molecular docking study '
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