Astragalin for COVID-19

The toxicological risk and development of resistance associated with synthetic drugs and supplements can be reduced by focusing efforts on medicinal plants that are of interest in pharmacognostic research to find new drugs or templates for the development of new bioactive compounds. The parasitic plant Cuscuta spp. has significant pharmacological activity at the extract level, but there is limited data on the bioactivity of its chemical compounds. In the present study, we aimed to investigate the antiviral potential of extracts obtained from different parts of two species, C. campestris and C. epithymum. The two species clearly differ in their flavonoid profiles, which could also suggest different antiviral activities of the extracts. We used methanol and aqueous extracts, MDBK, VERO E6 clone 76 and BGM cell lines, HSV-1, HSV-2 strain DD (acyclovir-resistant), HCoV-229E and SARS-CoV-2, maximum tolerable concentration, the MTT test, the plaque-forming method and the HPLS-MS analysis. It was found that the metabolic composition varies depending on the host plant. We hypothesize that differences in the composition of the extracts lead to differences in antiviral activity. Some of the tested methanol extracts showed a pronounced inhibitory effect, both on replication and on extracellular virions, in relation to the ACV-resistant strain of HSV type 2 and SARS-CoV-2 in comparison with the other viral models used by us. The strongest antiviral effect was shown by the methanol extract of C. campestris with host Chenopodium spp. against SARS-CoV-2, as the virus inhibition was about 100%, and the virucidal effect showed a decrease in the viral titer by more than 2.5 lg. Based on the results obtained, we assume possible antagonistic interaction of individual metabolites in the total methanol extracts. Extract C3, applied at the maximum tolerable concentration and one level lower, inhibits SARS-CoV-2 about 100 percent. SARS-CoV-2-infected cells preserved mitochondrial activity and relatively preserved lysosomal activity; this is also the reason why the MTT test, as well as neutral red staining, is not applicable to this viral model propagated in the VERO E6 cell line.

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has been spreading globally for over 2 years, causing serious contagious disease and incalculable damage. The introduction of vaccines has slowed the spread of SARS‐CoV‐2 to some extent, but there remains a need for specific and effective treatment. The high chemical diversity and safety profiles of natural products make them a potential source of effective anti‐SARS‐CoV‐2 drugs. Cotton plant is one of the most important economic and medical crops and is the source of a large number of antiviral phytochemicals. In this work, we used SARS‐CoV‐2 main protein (Mpro) as the target to identify potential anti‐SARS‐CoV‐2 natural products in cotton. An in vitro assay showed that of all cotton tissues examined, cotton flower extracts (CFs) exhibited optimal inhibitory effects against Mpro. We proceeded to use the CF metabolite database to screen natural Mpro inhibitors by combining virtual screening and biochemical assays. We identified that several CF natural products, including astragalin, myricitrin, and astilbin, significantly inhibited Mpro with half‐maximal inhibitory concentrations (IC50s) of 0.13, 10.73, and 7.92 μm, respectively. These findings may serve as a basis for further studies into the suitability of cotton as a source of potential therapeutics for SARS‐CoV‐2.

(1) Background: The SARS-CoV-2 papain-like protease (PLpro) remains an underexplored antiviral target so far. The reduced efficacy of approved treatments against novel variants highlights the importance of developing new agents. This review aims to provide a comprehensive understanding of phytochemicals as inhibitors of PLpro, identify gaps, and propose novel insights for future reference. (2) Methods: A thorough literature search was conducted using Google Scholar, ScienceDirect, and PubMed. Out of 150 articles reviewed, 57 met inclusion criteria, focusing on SARS-CoV-2 PLpro inhibitors, excluding studies on other coronaviruses or solely herbal extracts. Data were presented class-wise, and phytochemicals were grouped into virtual, weak, modest, and potential inhibitors. (3) Results: Approximately 100 phytochemicals are reported in the literature as PLpro inhibitors. We classified them as virtual inhibitors (70), weak inhibitors (13), modest inhibitors (11), and potential inhibitors (6). Flavonoids, terpenoids, and their glycosides predominated. Notably, six phytochemicals, including schaftoside, tanshinones, hypericin, and methyl 3,4-dihydroxybenzoate, emerged as potent PLpro inhibitors with favorable selectivity indices and disease-mitigation potential; (4) Conclusions: PLpro stands as a promising therapeutic target against SARS-CoV-2. The phytochemicals reported in the literature possess valuable drug potential; however, certain experimental and clinical gaps need to be filled to meet the therapeutic needs.

AbstractBioactive compounds are secondary metabolites of plants. They offer diverse pharmacological properties. Peganum harmala is reported to have pharmaceutical effects like insecticidal, antitumor, curing malaria, anti-spasmodic, vasorelaxant, antihistaminic effect. Rosa brunonii has medicinal importance in its flower and fruits effective against different diseases and juice of leaf is reported to be applied externally to cure wounds and cuts. Dryopteris ramosa aqueous leaf extract is used to treat stomach ulcers and stomachaches. Each of these three medicinal plants have been indicated to have anticancer, antiviral, antioxidant, cytotoxic and antifungal effects but efficacy of their bioactive compounds remained unexplored. Study was aimed to explore In-vitro and In-silico anticancer, antiviral, antioxidant, cytotoxic and antifungal effects of bioactive compounds of above three medicinal plants. DPPH and ABTS assay were applied for assessment of antioxidant properties of compounds. Antibacterial properties of compounds were checked by agar well diffusion method. Brine shrimp lethality assay was performed to check cytotoxic effect of compounds. Molecular docking was conducted to investigate the binding efficacy between isolated compounds and targeted proteins. The compound isomangiferrin and tiliroside presented strong antioxidant potential 78.32% (± 0.213) and 77.77% (± 0.211) respectively in DPPH assay while harmaline showed 80.71% (± 0.072) at 200 µg/mL in ABTS assay. The compound harmine, harmaline and PH-HM 17 exhibited highest zone of inhibition 22 mm, 23 mm, 22 mm respectively against Xanthomonas while Irriflophenone-3-C-β- D-glucopyranoside showed maximum zone of inhibition 34 mm against E. coli. The compound isomangiferrin and vasicine contained strong antibacterial activity 32 mm and 22 mm respectively against S. aureus. The compound mangiferrin, astragalin, tiliroside, quercitin-3-O-rhamnoside showed maximum inhibitory zone 32 mm, 26 mm, 24 mm and 22 mm respectively against Klebsiella pneumoniae. Highest cytotoxic effect was observed by compound tiliroside i.e. 95% with LD50 value 73.59 µg/mL. The compound tiliroside showed the best binding mode of interaction to all targeted proteins presenting maximum hydrophobic interactions and hydrogen bonds. The binding affinity of tiliroside was − 17.9, − 14.9, − 14.6, − 13.8, − 12.8 against different proteins 6VAR, 5C5S, IEA3, 2XV7 and 6LUS respectively. Bioactive compounds are significant natural antioxidants, which could help to prevent the progression of various diseases caused by free radicals. Based on molecular docking we have concluded that phytochemicals can have better anticancer and antiviral potential.