English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

According to the 2021 Malaria report, 241 million clinical episodes with 627000 deaths penalty was estimated across the worldwide. However, mutation in the propeller domain of  Plasmodium falciparum  kelch 13 protein resulted in longer parasite clearance time following an artemisinin-based treatment and had a greater survival rate of ring-stage parasites even after a brief exposure to a high dose of artesunate. Clinical manifestations become more complex and worse with the emerging trend of drug resistance against artemisinin derivatives and the poor effectiveness of malaria vaccination drive. Steroidal lactone (withanolide) moiety (C-28) isolated from methanolic leaf extract  Withania somnifera  show a greater affinity towards Pfkelch 13 protein in comparison to the artemisinin derivatives (artesunate, artemether). The isolated compound was characterized to be withaferin A with a percentage yield of 29.01% w/w in chloroform fraction, 1.75% w/w in methanolic extract, and 0.29% w/w in raw leaf powder. Structure-based analysis shows that withaferin A (docking score −8.253, −9.802) has a higher affinity for two distinct binding pockets I and II of the  Plasmodium falciparum  kelch 13 protein than artesunate (docking score −4.470, −3.656). Further, Gibbs binding free energy signifies thermodynamic stability of the docked complex of withaferin A (-43.25, −43.76 Kcal/mol) in comparison to artesunate docked complex (-8.49, −5.75 Kcal/mol). The pharmacokinetic profile of withaferin A shows more drug-likeness characteristics without violating Jorgensen’s rule of three, and Lipinski's rule of five. Hence above experimental findings suggest withaferin A could be a suitable therapeutic adjunct for preclinical evaluation of antimalarial potentiality in artemisinin-resistant malaria.HIGHLIGHTsMalaria is a life-threatening parasitic disease caused by Plasmodium species.The emerging trend of artemisinin resistance and severe side effects (CNS and cardiotoxicity) are the potential challenges faced by antimalarial therapeutics.Artemisinin-mimic potentiality (ROS-mediated antiparasitic activity) of withaferin A shows a strong affinity towards artemisinin resistance  Plasmodium falciparum  kelch 13 protein.The pharmacokinetic profiling of the withaferin A signifies its drug-likeness characteristics without violating Jorgensen’s rule of three, and Lipinski's rule of five.Based on molecular docking and pharmacokinetic profiling, withaferin A could be a suitable therapeutic adjunct for preclinical investigation of antimalarial potentiality in artemisinin-resistant malaria. Malaria is a life-threatening parasitic disease caused by Plasmodium species. The emerging trend of artemisinin resistance and severe side effects (CNS and cardiotoxicity) are the potential challenges faced by antimalarial therapeutics. Artemisinin-mimic potentiality (ROS-mediated antiparasitic activity) of withaferin A shows a strong affinity towards artemisinin resistance  Plasmodium falciparum  kelch 13 protein. The pharmacokinetic profiling of the withaferin A signifies its drug-likeness characteristics without violating Jorgensen’s rule of three, and Lipinski's rule of five. Based on molecular docking and pharmacokinetic profiling, withaferin A could be a suitable therapeutic adjunct for preclinical investigation of antimalarial potentiality in artemisinin-resistant malaria. Communicated by Ramaswamy H. Sarma

journal of biomolecular structure and dynamics

Isolation and structure elucidation of a steroidal moiety from  Withania somnifera  and  in silico  evaluation of antimalarial efficacy against artemisinin resistance  Plasmodium falciparum  kelch 13 protein