Nicotiflorin for COVID-19

Papaya leaves have been used as food and traditional herbs for the treatment of cancer, diabetes, asthma, and virus infections, but the active principle has not been understood. We hypothesized that the anti-inflammatory activity could be the predominant underlying principle. To test this, we extracted papaya leaf juice with different organic solvents and found that the ethyl acetate (EA) fraction showed the most outstanding anti-inflammatory activity by suppressing the production of nitric oxide (NO, IC50 = 24.94 ± 2.4 μg/mL) and the expression of pro-inflammatory enzymes, such as inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2), and cytokines including interleukins (IL-1β and IL-6), and a tumor necrosis factor (TNF-α) in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Transcriptomic analysis and Western blot results revealed its anti-inflammatory mechanisms were through the MAPK signaling pathway by inhibiting the phosphorylation of ERK1/2, JNKs, and p38 and the prevention of the cell surface expression of TLR4. Furthermore, we discovered that the EA fraction could inhibit the replication of alpha-coronavirus (HCoV-229E) and beta-coronavirus (HCoV-OC43 and SARS-CoV-2) and might be able to prevent cytokine storms caused by the coronavirus infection. From HPLC-QTOF-MS data, we found that the predominant phytochemicals that existed in the EA fraction were quercetin and kaempferol glycosides and carpaine. Counter-intuitively, further fractionation resulted in a loss of activity, suggesting that the synergistic effect of different components in the EA fraction contribute to the overall potent activity. Taken together, our results provide preliminary evidence for papaya leaf as a potential anti-inflammatory and anti-coronavirus agent, warranting further study for its use for human health promotion.

The SARS-CoV-2 infection continues triggering substantial distress to people since 2019. Many research investigationsconcerning viral pathogenesis regarding the manner in which the virus infects and multiplies within the host have led toconverging conclusions. Numerous studies have additionally demonstrated a strong link between ageing, mildinflammation, metabolic disorders and SARS-CoV-2 illness. According to a modest collection of knowledge, nutraceuticals arecapable of avoiding viral invasion and can reduce inflammation. Consequently, in this current work, we report a moleculardocking analysis for nutraceuticals from diverse plants against SARS-CoV-2 cysteine proteases PLpro (PDB ID: 7CJM) andRNA dependent RNA polymerase (RdRp, PDB ID: 6M71) which play major role in viral replication. The molecular dockingstudies showed that chicoric acid (7CJM : -8.617 Kcal/Mol, 6M71: -6.475) and rosemarinic acid (7CJM : -7.925 Kcal/Mol,6M71 : -8.323 Kcal/Mol) exhibited good docking scores with the selected targets, which were better when compared to that ofreference antiviral drugs Remdesivir and Favipiravir. The majority of the nutraceuticals assessed by Qikprop displayedbeneficial pharmacological characteristics for human administration.

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

In this study, the possible interactions of 17 phytochemicals that were reported as the most abundant biomolecules of Hibiscus sabdariffa, including many organic acids as well as catechin and quercetin derivatives, with 3CLpro and PLpro proteases of SARS-CoV-2 have been investigated via molecular docking. Caffeoylshikimic acid/3CLpro showed the lowest binding energy (-7.72 kcal/mol) with seven H-bonds. The second-lowest binding energy was computed in the chlorogenic acid/3CLpro complex (-7.18 kcal/mol), which was found to form 6 H-bonds. Also, low binding energies of cianidanol (-7.10 kcal/mol), cryptochlorogenic acid (-6.67 kcal/mol), and kaempferol (-6.82 kcal/mol) were calculated to 3CLpro with several H-bond interactions. Nelfinavir (-10.16 kcal/mol) and remdesivir (-6.40 kcal/mol), which have been used against COVID-19, were obtained to have low binding energies to 3CLpro with 3 H-bond formations each. On the other hand, the nicotiflorin/PLpro complex, which had the lowest binding energy (-7.40 kcal/mol), was found to have only 1 H-bond interaction. The second-lowest binding energy was reported in chlorogenic acid/PLpro (-7.20 kcal/mol), which was found to possess four H-bonds. On the other hand, epigallocatechin gallate/PLpro, which was shown to have a -5.95 kcal/mol binding energy, was found to form 8 H-bond interactions. Furthermore, the quercetin pentosylhexoside/PLpro complex was monitored to have low binding energy (-6.54 kcal/mol) with 9 H-bonds, which stands as the highest number of H-bonds in all complexes. Therefore, several molecules of Hibiscus sabdariffa were found to have strong binding affinity to the main proteases of SARS-CoV-2. This study suggests many compounds, including caffeoylshikimic acid and nicotiflorin, to inhibit 3CLpro and PLpro activities. As a result, numerous chemicals derived from Hibiscus sabdariffa have the potential to be employed therapeutically against SARS-CoV-2 infection.