Johora, F. T. | bioRxiv Science

bioRxiv2020

Insecticide resistance status of Aedes aegypti in Bangladesh

BackgroundArboviral diseases including dengue and chikungunya are major public health concern in Bangladesh, with unprecedented levels of transmission reported in recent years. The primary approach to control these diseases is control of Aedes aegypti using pyrethroid insecticides. Although chemical control is long-practiced, no comprehensive analysis of Ae. aegypti susceptibility to insecticides has previously been conducted. This study aimed to determine the insecticide resistance status of Ae. aegypti in Bangladesh and investigate the role of detoxification enzymes and altered target site sensitivity as resistance mechanisms. MethodsAedes eggs were collected using ovitraps from five districts across the country and in eight neighborhoods of the capital city Dhaka from August to November 2017. CDC bottle bioassays were conducted for permethrin, deltamethrin, malathion, and bendiocarb using 3-5-day old F0-F2 non-blood fed female mosquitoes. Biochemical assays were conducted to detect metabolic resistance mechanisms and real-time PCR was performed to determine the frequencies of the knockdown resistance (kdr) mutations Gly1016, Cys1534, and Leu410. ResultsHigh levels of resistance to permethrin were detected in all Ae. aegypti populations, with mortality ranging from 0 - 14.8% at the diagnostic dose. Substantial resistance continued to be detected against higher (2X) doses of permethrin (5.1 - 44.4% mortality). Susceptibility to deltamethrin and malathion varied between populations while complete susceptibility to bendiocarb was observed in all populations. Significantly higher levels of esterase and oxidase activity were detected in most of the test populations as compared to the susceptible reference Rockefeller strain. A significant association was detected between permethrin resistance and the presence of Gly1016 and Cys1534 homozygotes. The frequency of kdr alleles varied across the Dhaka populations, and Leu410 was not detected in any of the tested populations. ConclusionsThe detection of widespread pyrethroid resistance and multiple mechanisms highlights the urgency for implementing alternate Ae. aegypti control strategies. In addition, implementing routine monitoring of insecticide resistance in Ae. aegypti in Bangladesh will lead to a greater understanding of susceptibility trends over space and time, thereby enabling the development of improved control strategies.

microbiology↗

bioRxiv2020

The Essential Facts of Wuhan Novel Coronavirus Outbreak in China and Epitope-based Vaccine Designing against 2019-nCoV

Wuhan Novel Coronavirus disease (COVID-19) outbreak has become a global outbreak which has raised the concern of scientific community to design and discover a definitive cure against this deadly virus which has caused deaths of numerous infected people upon infection and spreading. To date, no antiviral therapy or vaccine is available which can effectively combat the infection caused by this virus. This study was conducted to design possible epitope-based subunit vaccines against the SARS-CoV-2 virus using the approaches of reverse vaccinology and immunoinformatics. Upon continual computational experimentation three possible vaccine constructs were designed and one vaccine construct was selected as the best vaccine based on molecular docking study which is supposed to effectively act against SARS-CoV-2. Later, molecular dynamics simulation and in silico codon adaptation experiments were carried out in order to check biological stability and find effective mass production strategy of the selected vaccine. Hopefully, this study will contribute to uphold the present efforts of the researches to secure a definitive treatment against this lethal virus.

immunology↗

bioRxiv2020

Curcumin Analogues as the Inhibitors of TLR4 Pathway in Inflammation and Their Drug Like Potentialities: A Computer-based Study

In this study Curcumin and their different analogues have been analyzed as the inhibitors of signaling proteins i.e., Cycloxygenase-2 (COX-2), Inhibitor of Kappa{beta} Kinase (IKK) and TANK binding kinase-1 (TBK-1) of Toll Like Receptor 4 (TLR4) pathway involved in inflammation using computational tools. Multiple analogues showed better binding affinity than the approved drugs for the respective targets. Upon continuous computational exploration 6-Gingerol, Yakuchinone A and Yakuchinone B were identified as the best inhibitors of COX-2, IKK and TBK-1 respectively. Then their drug like potentialities were analyzed in different experiments where they also performed sound and similar. Hopefully, this study will uphold the efforts of researchers to identify anti-inflammatory drugs from natural sources.

pharmacology and toxicology↗