ABSTRACT
Coronaviruses have caused enough devastation in the last two decades. These viruses have some rare features while sharing some common features. Novel coronavirus disease (nCoV-19) caused an outbreak with a fatality rate of 5%. It emerged from China and spread into many countries. The present research focused on genome analysis of Indian nCoV-19 Isolate and its translational product subjected to homology modeling and its subsequent molecular simulations to find out potent FDA approved drug for treating COVID-19. Phylogenetic analysis of SARS-CoV-2 Indian isolate shows close resemblance with 17 countries SARS-CoV-2 isolates. Homology modeling of four non-structural proteins translational product of Indian SARS-CoV-2 genome shows high similarity and allowed regions with the existing PDB deposited SARS-CoV-2 target proteins. Finally, these four generated proteins show more affinity with cobicistat, remdesivir and indinavir out of 14 screened FDA approved drugs in molecular docking which is further proven by molecular dynamics simulation and MMGBSA analysis of target ligand complex with best simulation trajectories. Overall our present research findings is that three proposed drugs namely cobicistat, remdesivir and indinavir showed higher interaction with the model SARS-CoV-2 viral target proteins from the Indian nCoV-19 isolate. These compounds could be used as a starting point for the creation of active antiviral drugs to combat the deadly COVID-19 virus during global pandemic and its subsequent viral infection waves across the globe.Communicated by Ramaswamy H. Sarma.
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)-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.