The outbreak of novel coronavirus disease (COVID-19) caused by SARS-CoV-2 poses a serious threat to human health and world economic activity. There is no specific drug for the treatment of COVID-19 patients at this moment. Traditionally, people have been using spices like ginger, fenugreek and onion, etc. for the remedy of a common cold. This work identifies the potential inhibitors of the main protease (M^pro) and spike (S) receptor of SARS-CoV-2 from 10 readily available spices. These two proteins, S and M^pro, play an important role during the virus entry into the host cell, and replication and transcription processes of the virus, respectively. To identify potential molecules an in-house databank containing 1040 compounds was built-up from the selected spices. Structure-based virtual screening of this databank was performed with two important SARS-CoV-2 proteins using Glide. Top hits resulted from virtual screening (VS) were subjected to molecular docking using AutoDock 4.2 and AutoDock Vina to eliminate false positives. The top six hits against M^pro and top five hits against spike receptor subjected to 130 ns molecular dynamic simulation using GROMACS. Finally, the compound 1-, 2-, 3- and 5-M^pro complexes, and compound 17-, 18-, 19-, 20- and 21- spike receptor complexes showed stability throughout the simulation time. The ADME values also supported the drug-like nature of the selected hits. These nine compounds are available in onion, garlic, ginger, peppermint, chili and fenugreek. All the spices are edible and might be used as home remedies against COVID-19 after proper biological evaluation. Communicated by Ramaswamy H. Sarma

The recent outbreak of the 2019 novel coronavirus disease (COVID-19) has been proved as a global threat. No particular drug or vaccine has not yet been discovered which may act specifically against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and causes COVID-19. For this highly infectious virus, 3CL-like main protease (3CL^pro) plays a key role in the virus life cycle and can be considered as a pivotal drug target. Structure-based virtual screening of DrugBank database resulted in 20 hits against 3CL^pro. Atomistic 100 ns molecular dynamics of five top hits and binding energy calculation analyses were performed for main protease-hit complexes. Among the top five hits, Nafarelin and Icatibant affirmed the binding energy (g_MMPBSA) of –712.94 kJ/mol and –851.74 kJ/mol, respectively. Based on binding energy and stability of protein-ligand complex; the present work reports these two drug-like hits against SARS-CoV-2 main protease. Communicated by Ramaswamy H. Sarma

Glycogen synthase kinase-3 (GSK-3) is a protein kinase containing threonine or serine amino acid residues. GSK-3 was first discovered in 1980 as a regulatory protein kinase, Glycogen synthase (GS) enzyme, which is responsible for the conversion of glycogen from glucose with the help of uridine diphosphate glucose (UDP-Glu) residue. GSK-3 has two isoforms present in human beings, namely GSK-3 α (serine residue at 21 position) and GSK-3 β (serine residue at 9 position). GSK-3 has two terminals, namely C- terminal and N- terminal. C-terminal of GSK-3 resembles α- helix conformation, which acts as an activator loop and is responsible for positioning residues in ATP binding and catalysis of substrates. On the other hand, the N- terminal of GSK-3 resembles β- strand conformation, which acts as an inhibitory loop; having a tyrosine molecule at 216 positions, it is essential for the complete GSK-3 activity. N- terminal of GSK-3 is responsible for ATP binding activity and exhibits various biological activities like cell signaling, gene induction following activation of T cell receptor, apoptosis, protein translation, glycogen metabolism, and inflammatory process. Activation of GSK-3 leads to pro-inflammatory actions, i.e. an increase in the binding activity of NF-kB (pro-inflammatory genes), increase in the transactivation activity of NF-kB, increase in the phosphorylation of p105, and a decrease in the transactivation activity of C/EBPβ (anti- inflammatory genes), resulting in a large number of prevalent diseases such as diabetes, cancer, neurodegenerative diseases, psychiatric diseases, mood disorders, etc. Glycogen synthase kinase inhibitors (GSK-3 inhibitors) are various chemotypes and have different mechanisms of actions. They are obtained from different sources such as natural products, synthetic ATP as well as non-ATP competitive inhibitors along with substrate-competitive inhibitors. The inhibitors of GSK3 have proven to possess very potent anti-inflammatory action. GSK-3 inhibitors are useful for treating different prevalent disorders, such as neurodegenerative diseases, including Alzheimer's disease, hyperglycemia, cancer disease, and mood disorders like depression, etc. In this review, we have highlighted the evidence regarding the description and types of GSK, inflammation process, and the factors affecting inflammation, the relationship between inflammation and GSK, GSK3 inhibitors, and finally, the impact of various natural as well as synthetic GSK3 inhibitors having anti-inflammatory activity.

Coronavirus disease 2019 (COVID-19) has created a global human health crisis and economic setbacks. Lack of specific therapeutics and limited treatment options against COVID-19 has become a new challenge to identify potential hits in order to develop new therapeutics. One of the crucial life cycle enzymes of SARS-CoV-2 is main protease (M^pro), which plays a major role in mediating viral replication, makes it an attractive drug target. Virtual screening and three times repeated 100 ns molecular dynamics simulation of the best hits were performed to identify potential SARS-CoV-2 M^pro inhibitors from the available compounds of an antiviral plant Moringa oleifera. Three flavonoids isorhamnetin (1), kaempferol (2) and apigenin (3) showed good binding affinity, stable protein-ligand complexes throughout the simulation time, high binding energy and similar binding poses in comparison with known SARS-CoV-2 M^pro inhibitor baicalein. Therefore, different parts of M. oleifera may be emerged as a potential preventive and therapeutic against COVID-19. Communicated by Ramaswamy H. Sarma Graphical Abstract

A series of 2-substituted and 2,3-substituted quinazolin -4(3H)-one derivatives were designed and synthesized based on the structure of febrifugine. The structures of the new compounds were confirmed by spectral analysis. The in vivo biological activity test results indicated that those compounds exhibited antimalarial activities against Plasmodium berghei in mice, at a dose of 5 mg/kg. Compared to Chloroquine and Artemisinin, these compounds have the advantages of shorter synthetic routes and consequently are highly cost effective in nature.

Febrifugine and its derivatives are effective against Plasmodium falciparum. Using PHASE algorithm, a five-point pharmacophore model with two hydrogen bond acceptor (A), one positively ionizable (P) and two aromatic rings (R), was developed to derive a predictive ligand-based statistically significant 3D-quantitative structure-activity relationship (QSAR) model (r ² = 0.972, SD = 0.3, F = 173.4, Q ² = 0.712, RMSE = 0.3, Person-R = 0.94, and r ^{2 pred} = 0.8) to explicate the structural attributes crucial for antimalarial activity. The developed pharmacophore model and 3D QSAR model can be a substantial tool for virtual screening and related antimalarial drug discovery research.