Mulberroside E

Identification of natural inhibitors against prime targets of SARS-CoV-2 using molecular docking, molecular dynamics simulation and MM-PBSA approaches.[Pubmed:33183178]

J Biomol Struct Dyn. 2022 Apr;40(7):3296-3311.

The recently emerged COVID-19 has been declared a pandemic by the World Health Organization as to date; no therapeutic drug/vaccine is available for the treatment. Due to the lack of time and the urgency to contain the pandemic, computational screening appears to be the best tool to find a therapeutic solution. Accumulated evidence suggests that many phyto-compounds possess anti-viral activity. Therefore, we identified possible phyto-compounds that could be developed and used for COVID-19 treatment. In particular, molecular docking was used to prioritize the possible active phyto-compounds against two key targets namely RNA dependent RNA polymerase (RdRp) and main protease (M(pro)) of SARS-CoV-2. In this study, an antiviral drug- Remdesivir (RdRp inhibitor) and Darunavir (M(pro) inhibitor) are used as reference drugs. This study revealed that phyto-molecules- Mulberroside-A/C/E/F, Emblicanin A, Nimbolide, and Punigluconin showed high binding affinity against RdRp while Andrographolides, Mulberrosides, Anolignans, Chebulic acid, Mimusopic acid, and Punigluconin showed better binding affinity against M(pro) as compared with the reference drug. Furthermore, ADME profiles validated the drug-likeness properties of prioritized phyto-compounds. Besides, to assess the stability, MD simulations studies were performed along with reference inhibitors for M(pro) (Darunavir) and RdRp (Remdesivir). Binding free energy calculations (MM-PBSA) revealed the estimated value (DeltaG) of M(pro)_Darunavir; M(pro)_Mulberroside E; RdRp_Remdesivir and RdRp_Emblicanin A were -111.62 +/- 6.788, -141.443 +/- 9.313, 30.782 +/- 5.85 and -89.424 +/- 3.130 kJmol(-1), respectively. Taken together, the study revealed the potential of these phyto-compounds as inhibitors of RdRp and M(pro) inhibitor that could be further validated against SARS-CoV-2 for clinical benefits.Communicated by Ramaswamy H. Sarma.

Inhibition of xanthine and monoamine oxidases by stilbenoids from Veratrum taliense.[Pubmed:11301865]

Planta Med. 2001 Mar;67(2):158-61.

The bioassay guided refractionation of the methanol extract of roots and rhizomes of Veratrum taliense (Liliaceae) yielded five stilbenoids: veraphenol, resveratrol, piceid, isorhapontin, and Mulberroside E, all inhibiting xanthine oxidase (XO, EC 1.2.3.2.) in vitro in a dose-dependent manner with IC50 values of 11.0, 96.7, 66.1, 70.0, and 78.4 microM, respectively. Veraphenol and Mulberroside E were found to be mixed XO inhibitors with the Ki and Ki data of the former being 32.8 and 239.3 microM, and those of latter 32.5 and 13.8 microM, respectively. However, the inhibition on the enzyme by resveratrol, isorhapontin, and piceid was shown to be competitive with their Ki values of 9.7, 19.1, and 14.3 microM, respectively. Among the five stilbenoids, veraphenol and resveratrol were also revealed to inhibit competitively monoamine oxidase A (MAO, EC 1.4.3.4) with IC50 values at 38.0 and 26.6 microM, and Ki data 36.4 and 47.3 microM, respectively. However, none of the stilbenoids was inhibitory on MAO B in our assay. The structure-activity relationship examination showed that glycosylation of the stilbenoids could reduce the inhibition on XO and diminish the activity against MAO A, indicating that the free phenolic hydroxy group of the compounds was most likely essential for these bioactivities.