The role of autophagy in controlling SARS-CoV-2 infection: An overview on virophagy-mediated molecular drug targets

Autophagy-dependent cell death is a prominent mechanism that majorly contributes to homeostasis by maintaining the turnover of organelles under stressful conditions. Several viruses, including coronaviruses (CoVs), take advantage of cellular autophagy to facilitate their own replication. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a beta-coronavirus (β-CoVs) that mediates its replication through a dependent or independent ATG5 pathway using specific double-membrane vesicles that can be considered as similar to autophagosomes. With due attention to several mutations in NSP6, a nonstructural protein with a positive regulatory effect on autophagosome formation, a potential correlation between SARS-CoV-2 pathogenesis mechanisms and autophagy can be expected. Certain medications, albeit limited in number, have been indicated to negatively regulate autophagy flux, potentially in a way similar to the inhibitory effect of β-CoVs on the process of autophagy. However, there is no conclusive evidence to support their direct antagonizing effect on CoVs. Off-target accumulation of a major fraction of FDA-approved autophagy modulating drugs may result in adverse effects. Therefore, medications that have modulatory effects on autophagy could be considered as potential lead compounds for the development of new treatments against this virus. This review discusses the role of autophagy/virophagy in controlling SARS-CoV-2, focusing on the potential therapeutic implications.     

Effect of plant extracts on the mortality of root-knot nematodes’ J2, Meloidogyne javanica

Root-knot nematode, Meloidogyne javanica, is a major problem confronting greenhouse’s productions, field crops, vegetables, grapevines and almond rootstocks in Kermanshah province, Iran. Nematicides are not affordable to control this nematode. In the search for alternatives to chemicals control of nematodes, this research has dealt with nematicidal effects of crude herbal extracts on the root-knot nematodes. This study aimed to evaluate the effect of 21 endemic and exotic herbal extracts belong to 12 families of flowering plants in comparison with chicken manure and chemical nematicide (Temik) to control root-knot nematodes in in vitro conditions. The nematodes were pured and mass multiplied on tomato in the soil at greenhouse conditions. In order to study the effect of herbal extracts on mortality of second-stage juveniles (J₂), a 6?mL of each extract was poured in sterilised Petri dish and 54?±?4 juveniles were added. Distilled water was used as control and treatments replicated four times and incubated at ambient temperature. The LC₅₀ value of each extract was determined by assessing the mortality of juveniles (in the range of 5–95%) after 24, 48 and 72 h. Comparison between LC₅₀ value of the extracts indicated that Cinnamomum zeylanicum and Eugenia caryophillata are the most effective crude extracts on the mortality of juveniles and they were 15.4 and 17.9?mg?mL^?1, respectively. Meanwhile, the extract of tobacco, ferulago, garlic, eucalyptus, persan lilac, rattle, oliveria, licorice, russian knapweed, turnsole, sicilian sumac and chicken manure did not have any antinematode activity against fresh second-stage juveniles of the root-knot nematode.     

COVID-19 under spotlight: A close look at the origin,transmission, diagnosis,and treatment of the 2019-nCoV disease

Months after the outbreak of a new flu-like disease in China, the entire world is now in a state of caution. The subsequent less-anticipated propagation of the novel coronavirus disease, formally known as COVID-19, not only made it to headlines by an overwhelmingly high transmission rate and fatality reports, but also raised an alarm for the medical community all around the globe. Since the causative agent, SARS-CoV-2, is a recently discovered species, there is no specific medicine for downright treatment of the infection. This has led to an unprecedented societal fear of the newly born disease, adding a psychological aspect to the physical manifestation of the virus. Herein, the COVID-19 structure, epidemiology, pathogenesis, etiology, diagnosis, and therapy have been reviewed.     

Cost-effectiveness of integrated pest management compared with insecticidal spraying against the German cockroach in apartment buildings

This study assessed the cost and effectiveness of an integrated pest management (IPM) program using hydramethylnon gel baits compared with conventional spraying for controlling the German cockroach, Blattella germanica (L.) (Blattodea: Blattellidae), in two residential buildings in Yasuj, Iran. The IPM approach was based on educational programs using pamphlets, posters and lectures, sanitation using vacuuming and application of hydramethylnon gel baits. Conventional approach used cypermethrin (10% EC) on baseboard and cracks-and-crevices. Sticky traps were used as tools for monitoring cockroach population densities. The IPM approach reduced (943%) the rate of insecticide application compared to the conventional spray. Cockroach populations in the IPM treatment were significantly reduced from an average of 12.2 ± 3.01 cockroaches per unit before treatment to zero cockroach per unit by week four and thereafter. Cockroach populations in the conventional spray treatment were reduced from an average of 11.5 ± 4.43 cockroaches per unit before treatment to an average of 3.4 ± 0.99 cockroach per unit after 11 weeks of post treatment. The IPM treatment improved 100% of infested units compared to 78% for spray treatment to obtain a clean level of infestation (< 1cockroach per trap per unit). The results suggest that the intervention by IPM using hydramethylnon gel baits significantly reduced cockroach infestation compared to cypermethrin spray throughout the 11 weeks of post-treatment period. However, within the study period, the IPM system involving gel baits, educational program and sanitation was 363.2% more expensive than the conventional method.     

Flavonoids as potent allosteric inhibitors of protein tyrosine phosphatase 1B: molecular dynamics simulation and free energy calculation

Protein tyrosine phosphatase 1B (PTP1B) is a member of the PTP superfamily which is considered to be a negative regulator of insulin receptor (IR) signaling pathway. PTP1B is a promising drug target for the treatment of type 2 diabetes, obesity, and cancer. The existence of allosteric site in PTP1B has turned the researcher’s attention to an alternate strategy for inhibition of this enzyme. Herein, the molecular interactions between the allosteric site of PTP1B with three non-competitive flavonoids, (MOR), (MOK), and (DPO) have been investigated. Three ligands were docked into allosteric site of the enzyme. The resulting protein–ligand complexes were used for molecular dynamics studies. Principal component and free-energy landscape (FEL) as well as cluster analyses were used to investigate the conformational and dynamical properties of the protein and identify representative enzyme substrates bounded to the inhibitors. Per residue energy decomposition analysis attributed dissimilar affinities of three inhibitors to the several hydrogen bonds and non-bonded interactions. In conclusion, our results exhibited an inhibitory pattern of the ligands against PTP1B.     

Prevalence of Non-Tuberculosis Mycobacterial Infections among Tuberculosis Suspects in Iran: Systematic Review and Meta-Analysis

Introduction

The infections due to Non-Tuberculosis Mycobacteria (NTM) are becoming an important health problem in many countries in the world. Globally, an increase in NTM infections has been reported from many countries around the world. However, limited information is available about the prevalence of NTM infections in Iran.

Material and Methods

The data of the prevalence of NTM infections were collected from databases such as PubMed, Web of science, Cochrane Library, Embase, Scopus, Iranmedex, and Scientific Information Database. Comprehensive Meta-Analysis (V2.0, Biostat) software was used to analyze the data.

Results

The meta-analyses showed that the prevalence of NTM infections was 10.2% (95% confidence interval [95% CI] 6.3-15.9) among culture-positive cases of tuberculosis (TB) in Iran. The further stratified analyses indicated that the prevalence of NTM was higher in studies that were done after year 2000. Additionally, M. simiae (43.3% [95% CI 36.8-50.0]), M. intracellucar (27.3% [95% CI 0.7-95.5]) and M. fortuitum (22.7% [95% CI 16.1-30.9]) were the most prevalent NTM species, respectively.

Discussion

The relatively high prevalence of NTM infections (10.2%) among culture positive cases for TB underlines the need for greater enforcement of infection control strategies. Establishment of appropriate diagnostic criteria and management guidelines for NTM diseases and expanding the number and quality of regional reference laboratories may facilitate more accurate action for prevention and control of NTM infections in Iran.     

Binding forces between a novel Schiff base palladium(II) complex and two carrier proteins: human serum albumi and β-lactoglobulin

Ligand binding studies on carrier proteins are crucial in determining the pharmacological properties of drug candidates. Here, a new palladium(II) complex was synthesized and characterized. The in vitro binding studies of this complex with two carrier proteins, human serum albumin (HSA), and β-lactoglobulin (βLG) were investigated by employing biophysical techniques as well as computational modeling. The experimental results showed that the Pd(II) complex interacted with two carrier proteins with moderate binding affinity (K_b ≈ .5 × 10⁴ M^?1 for HSA and .2 × 10³ M^?1 for βLG). Binding of Pd(II) complex to HSA and βLG caused strong fluorescence quenching of both proteins through static quenching mechanism. In two studied systems hydrogen bonds and van der Waals forces were the major stabilizing forces in the drug-protein complex formation. UV–Visible and FT-IR measurements indicated that the binding of above complex to HSA and βLG may induce conformational and micro-environmental changes of two proteins. Protein–ligand docking analysis confirmed that the Pd(II) complex binds to residues located in the subdomain IIA of HSA and site A of βLG. All these experimental and computational results suggest that βLG and HSA might act as carrier protein for Pd(II) complex to deliver it to the target molecules.