The Natural Ligand for Metalloproteinase-A Multifaceted Drug Target

Abstract

Metalloproteinases are a group of proteinases that extensively depend on metals for their biological activity, i.e., digesting proteins. Their role in developmental stages is indispensable. However, the same enzyme is also found to be a crucial mediator of several diseases like cancer, atheroma, arthritis, atherosclerosis, aneurysms, nephritis, tissue ulcers, brosis, etc. Exogenous metalloproteinases cause severe pathological effects which may even lead to mortality in humans and other higher animals. The major source of exogenous metalloproteinases is through venomous snake bites, which causes exposure of normal tissue later blood vessels to the proteinases. Though the structure and function of metalloproteinases are highly conserved, the accidental exposure causes severe irreversible damages of the exposed tissues and blood vessels which otherwise is a highly regulated process with the endogenous metalloproteinases. Hence, nding a suitable metalloproteinases inhibitor is of great biological importance in mitigating pathological effects. Batimastat is an approved drug prescribed for cancer which mediates its action by inhibiting metalloproteinases. Batimastat is a synthetic hydroxamate molecule with a simple structure that prompted the search for the existence of similar phytochemicals in plants. Computational analysis revealed interaction of Andrographis paniculata phytochemicals with the M domain of snake venom metalloproteinase active site amino acid residues namely ASN203, ARG293, PHE203, LEU206, LYS199, and ALA122 similar to that of the reference compound batimastat. 14acetylandrographolide, 14-deoxy-11,12 didehydroandrographolide, Andrograpanin, Isoandrographolide, and 14-deoxy-11-oxoandrographolide found to show maximum effectiveness against the metalloproteinase. Results of the current study show a possibility of developing potent drug targeting metalloproteinases from plants source.According to WHO, India is home to nearly twenty-four medically important snake species. Of which Russell's viper is classi ed under Category 1 (Highest medical importance) "highly venomous snakes that are common or widespread and cause numerous snakebites, resulting in high levels of morbidity, disability or mortality" (6). In India, Russell's viper is one of the 'Big four' snakes causing the maximum number of deaths due to snakebite (7). Snakebite statistics from 2000-2019 reveal Russell's viper is mainly responsible for bite constituting43%, followed by 21% unknown species, 18% Krait, 12% cobra (8).Hence SVMP is seen as a promising target for treatment against adverse effects of snake venom. This would reduce the mortality rate among snake-bitten patients. In traditional medicine practice, the decoction of various plant parts are been used in several parts of Asia, Africa, Central, and South America for treating snake envenomation (9). Andrographis paniculata is a remarkable plant used for treating various human ailments namely anti-cancer, antidiabetic, antibacterial, antimalarial, antiviral, cardiovascular, and hepatic p...

Research on Repressing Allergen Cry j 1 Released from Japanese Cedar Pollen Using Todomatsu Oil

“…where ∆G is the docking energy, Rcal is 1.987, and TK is 298.15 [46,[65][66][67]. A higher docking score indicates tighter adhesion of the oil component to the allergen Cry j 1.…”

“…A higher docking score indicates tighter adhesion of the oil component to the allergen Cry j 1. Ki value, the inhibitor dose necessary to cause half-maximum repression, represents the inhibitory effect of the oil component on the allergen [46,62,65,68]. A lower Ki value denotes a more powerful repression of oil components toward the allergen.…”

“…The docking score and inhibition constant, independently reflecting the adhesion and inhibitory potency of todomatsu oil components toward allergen Cry j 1 [46,62,65,68], are displayed in Figure 4a and Table A1. A higher docking score suggests a stronger docking of oil component to the allergen Cry j 1.…”