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

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

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.

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 −11.009 to −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.

The coronavirus disease (COVID-19) caused by SARS-CoV-2 is a big challenge and burning issue to the scientific community and doctors worldwide. Globally, COVID-19 has created a health disaster and adversely affects the economic growth. Although some vaccines have already emerged, no therapeutic medication has yet been approved by FDA for the treatment of COVID-19 patients. Traditionally, we have been using different medicinal plants like neem, tulsi, tea, and many spices like garlic, ginger, turmeric, black seed, onion, etc. for the treatment of flu-like diseases. In this paper, we are highlighting the recent research progress in the identification of natural products from the Indian medicinal plants and spices that have potential inhibition properties against SARS-CoV-2. This study will provide an initiative to stimulate further research by providing useful guidance to the medicinal chemists for designing new protease inhibitors effective against SARS-CoV-2 in future. Graphical Abstract In this review article, recent advances in the identification of natural products from the traditionally used Indian medicinal plants and spices that have potential inhibitory properties against SARS-CoV-2 proteins have been discussed. A prospective natural drug-like compound has minimum side effects. The in vitro study of the reported molecules might be provided a preventive measure against COVID-19 disease. Communicated by Ramaswamy H. Sarma