Toxicological Evaluation of a New Lepidopteran Insecticide, Flubendiamide, in Non-Target Drosophila melanogaster Meigen (Diptera: Drosophilidae)

MedComm – Future Medicine

2023

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Coronavirus disease‐19 (COVID‐19) is the global health emergency caused by SARS‐CoV‐2. Upon infection, antigenic determinants of the virus trigger massive production of proinflammatory/pyroptosis‐associated proteins, resulting in cytokine storm, tissue damage, and multiorgan failure. Therefore, these proinflammatory/pyroptosis‐associated mediators are promising therapeutic targets to combat COVID‐19. Epicatechin gallate (ECG) is a polyphenol found in green tea. It has antioxidative and anti‐inflammatory properties. Hence, in the present study, ECG was selected to explore its binding potential for inflammatory mediators such as interleukins, interferon‐γ (IFNγ), and tumor necrosis factor‐α (TNF‐α), along with their native receptors. In addition, the interacting potential of ECG with pyroptosis‐associated proteins, viz. caspases and BAX has also been investigated. Molecular docking analysis has revealed that ECG interacts with interleukins, IFNγ, TNF‐α, cytokine receptors, caspase‐1/4/11, and BAX with significant binding affinity. Several amino acid residues of these mediators were blocked by ECG through stable hydrogen bonds and hydrophobic contacts. ECG interacted with caspase‐11, BAX, and TNF‐R1 with better binding affinities. Therefore, the present in silico study indicates that ECG could be a potential drug to subvert cytokine storm and pyroptosis during COVID‐19.

Section: Discussionmentioning

confidence: 99%

Computational study unravels inhibitory potential of epicatechin gallate against inflammatory and pyroptosis‐associated mediators in COVID‐19

Rajak

MedComm – Future Medicine

2023

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“…John et al 76 demonstrated that vitamin E has the potential to ameliorate dimethoate and malathion-induced OS in rat erythrocytes. Therefore, like other chemicals, OPs contribute to OS and subsequent pathologies that can be ameliorated to some extent by vitamin E [77][78][79][80][81][82][83][84][85][86][87] (Table 1). Eroğlu et al 62 human erythrocytes treated with 1, 10, and 100 μM concentrations of diclorvos.…”

Section: Protective Potential Of Vitamin E Against Op Induced Toxicit...mentioning

confidence: 99%

Protective Potential of Vitamin C and E against Organophosphate Toxicity: Current Status and Perspective

Rajak

Roy

et al. 2022

JEOH

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Pesticides are an integral part of our daily life, used in agricultural fields, store rooms, residences and educational institutions to kill or repel pests. Several chemical subtypes of these compounds are available, of which organophosphate (OP) is major one. These are broad spectrum pesticides used to kill insect pests. OPs are useful but indeed they are most frequent reasons of pesticide poisoning across the globe. OP inhibits acetylcholinesterase activities that results in continuous hyper-excitable state of nicotinic and muscarinic receptors at neuromuscular junctions. Intentional or unintentional exposure to OPs causes abdominal pain, diarrhea, vomiting, muscular weakness, dementia, Central Nervous System (CNS) dysfunction and even death. Besides acetylcholinesterase inhibition, OPs are also known to trigger ROS generation within the cellular machinery which results in Oxidative Stress (OS). Free Radicals (FRs) are neutralized by antioxidant-defense system of the body. Vitamin C and vitamin E are the major exogenous antioxidants that scavenge a large amount of free radicals by donating their own electrons to FRs. This phenomenon reduces ROS and hence, OS is prevented. Therefore, vitamin C and E can be considered for daily dietary intake which might be providing prophylactic advantage against OP induced OS and pathophysiology in human beings.

“…MDCA is derived from Centella asiatica and is known to exert multiple pharmaceutical activities. Exposure to exogenous agents like xenobiotics and pathogens can elicit oxidative stress and subsequent health hazards. − MDCA has been reported to restore redox homeostasis, prevent oxidative stress, and maintain mitochondrial membrane potential. , Moreover, it upregulates anti-apoptotic proteins like Bcl-xL and Bcl-2 to impede cell death . MDCA has been demonstrated to impose anti-colitic effects.…”

Section: Introductionmentioning

confidence: 99%

In Silico Analysis Reveals the Inhibitory Potential of Madecassic Acid against Entry Factors of SARS-CoV-2

Mandi

Dutta³

et al. 2023

ACS Appl. Bio Mater.

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Coronavirus disease 19 (COVID-19) is the ongoing global health emergency caused by SARS-CoV-2 infection. The virus is highly contagious, affecting millions of people worldwide. SARS-CoV-2, with its trimeric spike glycoprotein, interacts with the angiotensin-converting enzyme 2 (ACE2) receptor and other co-receptors like basigin to invade the host cell. Moreover, certain host proteases like transmembrane serine proteases, furin, neuropilin 1 (NRP1), and endosomal cathepsins are involved in the priming of spike glycoproteins at the S1/S2 interface. This is critical for the entry of viral genome and its replication in the host cytoplasm. Vaccines and anti-SARS-CoV-2 drugs have been developed to overcome the infection. Nonetheless, the frequent emergence of mutant variants of the virus has imposed serious concerns regarding the efficacy of therapeutic agents, including vaccines that were developed for previous strains. Thus, screening and development of pharmaceutical agents with multi-target potency could be a better choice to restrain SARS-CoV-2 infection. Madecassic acid (MDCA) is a pentacyclic triterpenoid found in Centella asiatica. It has multiple medicinal properties like anti-oxidative, anti-inflammatory, and anti-diabetic potential. However, its implication as an anti- SARS-CoV-2 agent is still obscure. Hence, in the present in silico study, the binding affinities of MDCA for spike proteins, their receptors, and proteases were investigated. Results indicated that MDCA interacts with ligand-binding pockets of the spike receptor binding domain, ACE2, basigin, and host proteases, viz. transmembrane serine proteinase, furin, NRP1, and endosomal cathepsins, with greater affinities. Moreover, the MDCA–protein interface was strengthened by prominent hydrogen bonds and several hydrophobic interactions. Therefore, MDCA could be a promising multi-target therapeutic agent against SARS-CoV-2 infection.