Nigellidine for COVID-19

Abstract Background The recent outbreak of the Coronavirus pandemic resulted in a successful vaccination program launched by the World Health Organization. However, a large population is still unvaccinated, leading to the emergence of mutated strains like alpha, beta, delta, and B.1.1.529 (Omicron). Recent reports from the World Health Organization raised concerns about the Omicron variant, which emerged in South Africa during a surge in COVID-19 cases in November 2021. Vaccines are not proven completely effective or safe against Omicron, leading to clinical trials for combating infection by the mutated virus. The absence of suitable pharmaceuticals has led scientists and clinicians to search for alternative and supplementary therapies, including dietary patterns, to reduce the effect of mutated strains. Main body This review analyzed Coronavirus aetiology, epidemiology, and natural products for combating Omicron. Although the literature search did not include keywords related to in silico or computational research, in silico investigations were emphasized in this study. Molecular docking was implemented to compare the interaction between natural products and Chloroquine with the ACE2 receptor protein amino acid residues of Omicron. The global Omicron infection proceeding SARS-CoV-2 vaccination was also elucidated. The docking results suggest that DGCG may bind to the ACE2 receptor three times more effectively than standard chloroquine. Conclusion The emergence of the Omicron variant has highlighted the need for alternative therapies to reduce the impact of mutated strains. The current review suggests that natural products such as DGCG may be effective in binding to the ACE2 receptor and combating the Omicron variant, however, further research is required to validate the results of this study and explore the potential of natural products to mitigate COVID-19. Graphical abstract

Abstract Background The etiological agent for the coronavirus illness outbreak in 2019–2020 is a novel coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (COVID-19), whereas coronavirus disease pandemic of 2019 (COVID-19) has compelled the implementation of novel therapeutic options. Main body of the abstract There are currently no targeted therapeutic medicines for this condition, and effective treatment options are quite restricted; however, new therapeutic candidates targeting the viral replication cycle are being investigated. The primary protease of the severe acute respiratory syndrome coronavirus 2 virus is a major target for therapeutic development (MPro). Severe acute respiratory syndrome coronavirus 2, severe acute respiratory syndrome coronavirus, and Middle East respiratory syndrome coronavirus (MERS-CoV) all seem to have a structurally conserved substrate-binding domain that can be used to develop novel protease inhibitors. Short conclusion With the recent publication of the X-ray crystal structure of the severe acute respiratory syndrome coronavirus 2 Mm, virtual and in vitro screening investigations to find MPro inhibitors are fast progressing. The focus of this review is on recent advancements in the quest for small-molecule inhibitors of the severe acute respiratory syndrome coronavirus 2 main protease.

In December 2019, an outbreak of a respiratory disease called the coronavirus disease 2019 (COVID-19) caused by a new coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in Wuhan, China. The SARS-CoV-2, an encapsulated positive-stranded RNA virus, spread worldwide with disastrous consequences for people’s health, economies, and quality of life. The disease has had far-reaching impacts on society, including economic disruption, school closures, and increased stress and anxiety. It has also highlighted disparities in healthcare access and outcomes, with marginalized communities disproportionately affected by the SARS-CoV-2. The symptoms of COVID-19 range from mild to severe. There is presently no effective cure. Nevertheless, significant progress has been made in developing COVID-19 vaccine for different therapeutic targets. For instance, scientists developed multifold vaccine candidates shortly after the COVID-19 outbreak after Pfizer and AstraZeneca discovered the initial COVID-19 vaccines. These vaccines reduce disease spread, severity, and mortality. The addition of rapid diagnostics to microscopy for COVID-19 diagnosis has proven crucial. Our review provides a thorough overview of the historical development of COVID-19 and molecular and biochemical characterization of the SARS-CoV-2. We highlight the potential contributions from insect and plant sources as anti-SARS-CoV-2 and present directions for future research.

The novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) responsible for the 2019 coronavirus disease (COVID-19) has caused a global health challenge. The SARS-COV-2 main protease, 3CLpro/Mpro plays a critical role in the viral gene expression and replication and has been a major target for inhibiting viral maturation and enhancing host innate immune responses against COVID-19. In this study, we screened a library of 38 phytochemicals from Nigella sativa (blackseed), Trigonella foenum-graecum (Fenugreek) and Anona muricata (Soursop) potent medicinal plants with reported antiviral properties - in a molecular docking protocol on 3CLpro using Autodock4.0 tool implanted in PyRx followed by docking validation and insilico absorption, distribution, metabolism, excretion, and toxicology (ADMET) evaluations. The docking results were visualized using Accelrys Discovery Studio and Pymol software. Among the 38 ligands screened, 19 showed significant interaction through non-covalent hydrogen bonding, hydrophobic, and electrostatic interactions with binding affinities from -5.3kcal/mol to -8.1kcal/mol indicating significant binding interactions at the active site binding pocket. Another important interaction observed in the study which mostly involve the transfer of charges was pi-interactions such as Pi-Pi interaction, Pi-Alkyl interaction, Pi-Sulfur interaction, Pi- Sigma, and Pi-Pi stacking. The docking results revealed that phytochemicals from T. foenum-graecum showed more 3CLpro inhibitory potential compared to those from N. sativa and A. muricata. Insilico ADMET evaluations for drug-like and lead-like characteristics however demonstrated that only 8 ligands - apigenin, kaempferol, luteolin, dithymoquinone, naringenine, nornuciferine, quercetin and nigellidine were actually drug-like; showed best activities against 3CLpro, and lack hepatotoxicity effects while none was lead-like. Insilico results of this study further suggested that drug repurposing candidates, remdesivir, indinavir,hydroxychloroquine, chloroquine and ritonavir,exhibited various interactions with 3CLpro. Hence, further in vitro and in vivo studies are proposed.

COVID-19 has been a threat to the entire world for more than two years since its outbreak in December 2019 in Wuhan city of China. SARS-CoV-2, the causative agent, had been reported to mutate over time exposing new variants. To date, no impeccable cure for the disease has been unveiled. This study outlines an extensive in silico approach to scrutinize certain phytochemical compounds of Nigella sativa (mainly the black cumin seeds) targeting the spike protein and the main protease (Mpro) enzyme of the Omicron variant of SARS-CoV-2. The objective of this study is to investigate the extracted compounds with a view to developing a potential inhibitor against the concerned SARS-CoV-2 variant. The investigation contemplates drug-likeness analysis, molecular docking study, ADME and toxicity prediction, and molecular dynamics simulation which have been executed to elucidate different phytochemical and pharmacological properties of the tested compounds. Based on drug-likeness parameters, a total of 96 phytochemical compounds from N. sativa have been screened in the study. Interestingly, Nigelladine A among the compounds exhibited the highest docking score with both the targets with the same binding affinity which is −7.8 kcal/mol. However, dithymoquinone, kaempferol, Nigelladine B, Nigellidine, and Nigellidine sulphate showed mentionable docking scores. Molecular dynamics up to 100 nanoseconds were simulated under GROMOS96 43a1 force field for the protein-ligand complexes exhibiting the top-docking score. The root mean square deviations (RMSD), root mean square fluctuations (RMSF), radius of gyration (Rg), solvent accessible surface area (SASA), and the number of hydrogen bonds have been evaluated during the simulation. From the findings, the present study suggests that Nigelladine A showed the most promising results among the selected molecules. This framework, however, interprets only a group of computational analyses on selected phytochemicals. Further investigations are required to validate the compound as a promising drug against the selected variant of SARS-CoV-2.