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-, 3and 5-M pro complexes, and compound 17-, 18-, 19-, 20and 21spike 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.

Neuroblastoma is the most common extracranial solid tumor found in children and survival rate is extremely meager. HDAC8, a class I zinc-dependent enzyme, is a potential drug target for treatment of neuroblastoma and T cell lymphoma. Most of the HDAC8 inhibitors discovered till date contains a hydroxamic acid group which acts as a zinc binding group. The high binding affinity to the zinc and other ions results in adverse effects. Also, the non-selective inhibition of HDACs cause a variety of side effects. The objective of this is to identify structurally diverse, non-hydroxamate, novel, potential and selective HDAC8 inhibitors. A number of five featured pharmacophore hypotheses were generated using 32 known selective HDAC8 inhibitors. The hypotheses ADDRR.4 were selected for building 3D QSAR model. This model has an excellent correlation coefficient and good predictive ability, which was employed for virtual screening of Phase database containing 4.3 × 106 molecules. The resultant hits with fitness score >1.0 were optimized using in-silico ADMET (absorption, distribution, metabolism,  excretion, and toxicity) and XP glide docking studies. On the basis of pharmacophore matching, interacting amino acid residues, XP glide score, more affinity towards HDAC8 and less affinity towards other HDACs, and ADME results five hits- SD-01, SD-02, SD-03, SD-04 and SD-05 with new structural scaffolds,  non-hydroxamate were selected for in vitro activity study. SD-01 and SD-02 were found to be active in the nanomolar (nM) range. SD-01 had considerably good selectivity for HDAC8 over HDAC6 and SD-02 had marginal selectivity for HDAC6 over HDAC8. The compounds SD-01 and SD-02 were found to inhibit HDAC8 at concentrations (IC50) 9.0 nM and 2.7 nM, respectively.

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The recently emerged 2019 Novel Coronavirus (SARS-CoV-2) and associated COVID-19 disease cause serious or even fatal respiratory tract infection. Observing the spread, illness and death caused by COVID-19, the World Health Organization (WHO) declared COVID-19 a pandemic. To date, there is no approved therapeutics or effective treatment available to combat the outbreak. This urgent situation is pressing the world to respond with development of novel vaccine or a small molecule therapeutics for SARS-CoV-2. In line with these efforts, the structure of several proteins of SARS-CoV-2 has been rapidly resolved and made publicly available to facilitate global efforts to develop novel drug candidates. In this paper, we aim to find out the small molecule inhibitors for ADP-ribose phosphatase of SARS-CoV-2. In order to identify potential inhibitors, we applied sequential E-pharmacophore and structure-based virtual screening (VS) of MolPort database containing 113687 number of commercially available natural compounds using Glide module. Six potential inhibitors having admirable XP glide score range from À 11.009 to À 14.684 kcal/ mol and good binding affinity towards active sites were identified. All the molecules are commercially available for further characterization and development by scientific community. The in vitro activity of selected inhibitors can be done easily which will provide useful information for clinical treatment of novel coronavirus pneumonia.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) is highly pathogenic to humans and has created an unprecedented global health care threat. Globally, intense efforts are going on to discover a vaccine or new drug molecules to control the COVID‐19. However, till today, there is no effective therapeutics or treatment available for COVID‐19. In this study, we aim to find out potential small molecule inhibitors for SARS‐CoV‐2 main protease (M pro ) from the known DrugBank database version 5.1.8. We applied structure‐based virtual screening of the database containing 11875 numbers of drug candidates to identify potential hits for SARS‐CoV‐2 M pro inhibitors. Seven potential inhibitors having admirable XP glide score ranging from −15.071 to −8.704 kcal/mol and good binding affinity with the active sites amino acids of M pro were identified. The selected hits were further analyzed with 50 ns molecular dynamics (MD) simulation to examine the stability of protein‐ligand complexes. The root mean square deviation and potential energy plot indicates the stability of the complexes during the 50 ns MD simulation. The MM‐GBSA analysis also showed good binding energy of the selected hits (−83.2718 to −58.6618 kcal/mol). Further analysis revealed critical hydrogen bonds and hydrophobic interactions between compounds and the target protein. The compounds bind to biologically important regions of M pro , indicating their potential to inhibit the functionality of this component.