RESUMO
Human corona viral infection leads to acute breathing disease and death if not diagnosed and treated properly in time. The disease can be treated with the help of simple natural compounds, which we use in day-to-day life. These natural compounds act against several diseases but their drug targeting mechanism needs to be improved for more efficient and promising applications. In the present study five compounds (gingerol, thymol, thymohydroquinone, cyclocurcumin, hydrazinocurcumin) from three Indian medicinal plants (ginger, black cumin, turmeric) and its hyaluronic acid (HA) conjugates were docked against initially deposited spike structural proteins (PDB ID 6WPT) and its mutant variant D-614G (PDB ID 6XS6). Docking study result reveals that all the HA conjugates showed the most effective inhibitor of S-protein of initially deposited and D-614G variant forms of SARS-CoV-2. The compounds like Gingerol, Thymol, Thymohydroquinone, Cyclocurcumin, Hydrazinocurcumin, Hydroxychloroquinone, and hyaluronic acid conjugates inhibit the viral protein of both wild-type and mutated S-protein of SARS-CoV-2. The molecular docking studies of phytocompounds with initial deposited and variant spike protein targets show superior binding affinity than with the commercial repurposed viral entry inhibitor hydroxychloroquine. Further, the docking result was modeled using MD simulation study shows excellent simulation trajectories between spike proteins and HA conjugates spices constituents than its free form. DFT analysis was carried out to affirm the reason behind the highest binding affinity of HA conjugates over its free form towards SARS-CoV-2 spike protein targets. Further HA conjugates synthesis and its evaluation against SARS-CoV-2 in vitro studies are needed to prove our novel idea for an anti-viral drug.Communicated by Ramaswamy H. Sarma.
RESUMO
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)-1ß, IL-6, tumor necrosis factor-alpha (TNF-α) 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.Communicated by Ramaswamy H. Sarma.
