Immunomodulatory and anti-cytokine therapeutic potential of curcumin and its derivatives for treating COVID-19 – a computational modeling

Abstract

The unavailability of vaccine and medicines raised serious issues during COVID-19 pandemic and peoples from different parts of world relied on traditional medicine for their immediate recovery from COVID-19 and it found effective also. The current research aims to target COVID-19 immunological human host receptors i.e. angiotensin-converting enzyme (ACE)-2, interleukin (IL)-1b, IL-6, tumor necrosis factor-alpha (TNF-a) and protease-activated receptor (PAR)-1 using curcumin derivatives to prevent viral infection and control overproduction of early clinical responses of COVID-19. Targeting these host proteins will mitigate the infection and will filter out many complications caused by these proteins in COVID-19 patients. It is proven through computer-aided computational modeling approaches, total 30 compounds of curcumin and its derivatives were chosen. Drug-likeness parameters were calculated for curcumin and its derivatives and 20 curcumin analogs were selected for docking analysis. From docking analysis of 20 curcumin analogs against five chosen human host receptor targets reveals 11 curcumin analogs possess least binding affinity and best interaction at active sites subjected to absorption, distribution, metabolism, excretion (ADME) analysis. Density functional theory (DFT) analysis of five final shortlisted curcumin derivatives was done to show least binding affinity toward chosen host target protein. Molecular dynamics simulation (MDS) was performed to observe behavior and interaction of potential drug hydrazinocurcumin against target proteins ACE-2 and PAR-1. It was performed at 100 nanoseconds and showed satisfactory results. Finally, our investigation reveals that hydrazinocurcumin possesses immunomodulatory and anti-cytokine therapeutic potential against COVID-19 and it can act as COVID-19 warrior drug molecule and promising choice of drug for COVID-19 treatment, however, it needs further in vivo clinical evaluation to commercialize as COVID-19 drug.

Hyaluronic Acid - 2-Deoxy-D-Glucose Conjugate Act as a Promising Targeted Drug Delivery Option for the Treatment of COVID-19

“…In the drug discovery process the ADMET properties of the compounds have an important role to play as these properties are mostly accountable for failure of drugs in approximately 60% of the clinical trials cases and our previous In silico virtual drug screening studies for COVID-19 confirm that both anti-viral molecules from both natural and synthetic drugs show good agreement with the above statements [32][33][34][35].…”

Enhancement of Biological and Pharmacological Properties of an Encapsulated Polyphenol: Curcumin

“…CUR exhibits antiviral properties and several studies have reported that CUR interrupts viral infection processes by different mechanisms, including prevention of viral entry, inhibition of replication, directly targeting viral proteins, blocking particle production and gene expression [ 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 ]. CUR has been reported to be effective against SARS-CoV in in vitro studies [ 68 ] and more recently it has also been postulated that it may have antiviral effects against SARS-CoV2, the virus that causes COVID-19 [ 57 , 58 , 73 , 74 ]. Wen et al [ 68 ] reported that CUR inhibits SARS-CoV 3CL protease activity, which is vital for viral replication.…”

“…Wen et al [ 68 ] reported that CUR inhibits SARS-CoV 3CL protease activity, which is vital for viral replication. Other studies have postulated that CUR can interfere with SAR-CoV2 entry and replication by interacting with the S protein and angiotensin converting enzyme-2 (ACE2) protein [ 73 , 74 ]. On this basis it has been postulated that CUR may directly intervene in SARS-CoV-2 entry and or replication and prevent infection.…”

Aging and diabetes drive the COVID-19 forwards; unveiling nature and existing therapies for the treatment

“…Curcumin has the potential to inhibit SARS-CoV-2 infections as shown in some of the in silico studies [46][47][48]. However, further studies are required to evaluate curcumin's potential as an antiviral drug.…”