The high infectivity and mortality of novel coronavirus has caused a serious concern all over the
world. Still, there is no specific drug or preventive medication to treat SARS-CoV-2 infection
despite comprehensive analysis by the researchers. This study was designed to demonstrate the
efficacy of some phyto-chemical compounds against SARS-CoV-2 by using both structure and
ligand based virtual screening methods. A total of 33 plant metabolites were screened against
SARS-CoV-2 main protease proteins (MPP), Nsp9 RNA binding protein, spike receptor binding
domain and HR2 domain using a molecular docking approach. Results showed that three
metabolites, i.e., Limonin, Isoflavone, and Coumadin conferred maximum binding affinity with
all key proteins of SARS-CoV-2. For each viral protein, the critical binding sites and drug surface
hotspots have been unraveled. ADME analysis indicated that none of the compounds have adverse
effects that could decrease their drug-like properties. Moreover, toxicity pattern analysis also
unmasked the non-toxic nature of the top drug candidates. The RMSD values of top ligandmacromolecule complexes were less than 2 Å, while RMSF values showed regular atomic
fluctuations in the molecular dynamics study. Notably, most of the target class by top drug
candidates belonged to enzyme groups (e.g. oxidoreductases, protease, Kinase). Results of drug
similarity prediction revealed two approved structural analogs of Coumadin named Warfarin
(DB00682) and Phenprocoumon (DB00946) from DrugBank. In addition, Isoformononetin an
experimental drug analog of isoflavone could also be an option for the treatment of viral infections.
For limonin there was no analog found in drugbank. The study can pave the way for the creation
of effective SARS-CoV-2 medications and preventive measures. We highly recommend further in
vivo trials for the experimental validation of our findings
The deeper understanding of metastasis phenomenon and detection of drug targets could be a potential approach to minimize cancer mortality. In this study, attempts were taken to unmask novel therapeutics to prevent metastasis and cancer progression. Initially, we explored the physiochemical, structural and functional insights of three metastasis tumor antigens (MTAs) and evaluated some plant based bioactive compounds as potent MTA inhibitors. From 50 plant metabolites screened, isoflavone, gingerol, citronellal and asiatic acid showed maximum binding affinity with all three MTA proteins. The ADME analysis detected no undesirable toxicity that could reduce the drug likeness properties of top plant metabolites. Moreover, molecular dynamics studies revealed that the complexes were stable and showed minimum fluctuation at molecular level. We further performed ligand based virtual screening to identify similar drug molecules using a large collection of 3,76,342 compounds from DrugBank. The results suggested that several structural analogs (e.g. Tramadol, Nabumetone, DGLA, Hydrocortisone) may act as agonist to block the MTA proteins and inhibit cancer progression at early stage. The study could be useful to develop effective medications against cancer metastasis in future. Due to encouraging results, we highly recommend further in vitro and in vivo trials for the experimental validation of the findings.
The high infectivity and mortality of novel coronavirus has caused a serious concern all over the
world. Still, there is no specific drug or preventive medication to treat SARS-CoV-2 infection
despite comprehensive analysis by the researchers. This study was designed to demonstrate the
efficacy of some phyto-chemical compounds against SARS-CoV-2 by using both structure and
ligand based virtual screening methods. A total of 33 plant metabolites were screened against
SARS-CoV-2 main protease proteins (MPP), Nsp9 RNA binding protein, spike receptor binding
domain and HR2 domain using a molecular docking approach. Results showed that three
metabolites, i.e., Limonin, Isoflavone, and Coumadin conferred maximum binding affinity with
all key proteins of SARS-CoV-2. For each viral protein, the critical binding sites and drug surface
hotspots have been unraveled. ADME analysis indicated that none of the compounds have adverse
effects that could decrease their drug-like properties. Moreover, toxicity pattern analysis also
unmasked the non-toxic nature of the top drug candidates. The RMSD values of top ligandmacromolecule complexes were less than 2 Å, while RMSF values showed regular atomic
fluctuations in the molecular dynamics study. Notably, most of the target class by top drug
candidates belonged to enzyme groups (e.g. oxidoreductases, protease, Kinase). Results of drug
similarity prediction revealed two approved structural analogs of Coumadin named Warfarin
(DB00682) and Phenprocoumon (DB00946) from DrugBank. In addition, Isoformononetin an
experimental drug analog of isoflavone could also be an option for the treatment of viral infections.
For limonin there was no analog found in drugbank. The study can pave the way for the creation
of effective SARS-CoV-2 medications and preventive measures. We highly recommend further in
vivo trials for the experimental validation of our findings
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.