Computational model for lipid binding regions in phospholipase (Ves a 1) from Vespa venom

Abstract

The Thai banded tiger wasp (Vespa affinis) is a dangerous vespid species found in Southeast Asia, and its stings often result in fatalities due to the presence of lethal phospholipase A$$_{1}$$ 1 , known as Vespapase or Ves a 1. Developing anti-venoms for Ves a 1 using chemical drugs, such as chemical drug guide, remains a challenging task. In this study, we screened 2056 drugs against the opening conformation of the venom using the ZINC 15 and e-Drug 3D databases. The binding free energy of the top five drug candidates complexed with Ves a 1 was calculated using 300-ns-MD trajectories. Our results revealed that voxilaprevir had a higher binding free energy at the catalytic sites than other drug candidates. Furthermore, the MD simulation results indicated that voxilaprevir formed stable conformations within the catalytic pocket. Consequently, voxilaprevir could act as a potent inhibitor, opening up avenues for the development of more effective anti-venom therapeutics for Ves a 1.

Cu-Electrocatalysis Enables Vicinal Bis(difluoromethylation) of Alkenes: Unraveling Dichotomous Role of Zn(CF2H)2(DMPU)2 as Both Radical and Anion Source

“…12−14 These molecular substructures have demonstrated the ability to effectively merge the benefits of lipophilicity and metabolic stability, while concurrently maintaining the binding affinity by providing multiple hydrogen bonding sites (Figure 1B). 15 Due to this high promise of the combinational effect, significant contributions in developing synthetic methods to enable access to such substructures have recently been made. 16−30 Among these strategies, difluoromethylative difunctionalization of unsaturated C−C bonds has been pursued as a central strategy to access a range of difluoromethylalkanes, mainly owing to the prevalence of the starting materials and the predictability of the mechanistic pathways involved (Figure 1C).…”

“…There has been particular success in pharmaceutical agents which possess multiple hydrogen bond donors in the vicinal position (Figure A). , This success has spurred interest in exploring the presence of CF 2 H functionality in proximity to other heteroatom-based functional groups, presenting an intriguing prospect in drug design and development due to its unique combination of properties. − These molecular substructures have demonstrated the ability to effectively merge the benefits of lipophilicity and metabolic stability, while concurrently maintaining the binding affinity by providing multiple hydrogen bonding sites (Figure B) …”