David Carrasco

Bio: David Carrasco is an academic researcher from Centre national de la recherche scientifique. The author has contributed to research in topics: Anopheles gambiae & Transmission (medicine). The author has an hindex of 2, co-authored 2 publications receiving 165 citations.

Efficacy of vector control tools against malaria-infected mosquitoes

Abstract: Within mosquito vector populations, infectious mosquitoes are the ones completing the transmission of pathogens to susceptible hosts and they are, consequently, of great epidemiological interest. Mosquito infection by malaria parasites has been shown to affect several traits of mosquito physiology and behavior, and could interplay with the efficacy of control tools. In this study, we evaluated, in pyrethroid resistant Anopheles gambiae, the effect of mosquito infection with the human malaria parasite Plasmodium falciparum on the efficacy of nets treated with either the insecticide deltamethrin or the repellent DEET, measuring (i) mosquito success to pass through the net, (ii) blood-feeding on a host and (iii) chemicals-induced mortality. Infection of mosquitoes at non-infectious stage did not affect their success to pass through the net, to blood-feed, nor chemicals-induced mortality. At infectious stage, depending on replicates, infected mosquitoes had higher mortality rates than uninfected mosquitoes, with stronger effect in presence of DEET. This data evidenced a cost of infection on mosquito survival at transmissible stages of infection, which could have significant consequences for both malaria epidemiology and vector control. This stresses the need for understanding the combined effects of insecticide resistance and infection on the efficacy on control tools. Mosquito-borne diseases are considerable public health issues, mostly affecting populations in developing countries 1,2. To reduce their incidence, controlling vector mosquitoes and limiting their contact with human hosts remains the most effective strategy 3. One promising approach for achieving this goal would be to selectively target, within mosquito populations, individuals that are the most dangerous for humans 4. Particularly, mosquitoes carrying transmissible forms of pathogens in their salivary glands (i.e. infectious mosquitoes), are of great epidemiological relevance. Yet, the implementation of control means that could specifically reach infectious mosquitoes is dependent upon an extensive knowledge of the effects of mosquito infection on its behavior and physiology. Infection by pathogens has been shown to affect mosquito phenotypic traits 5. Malaria-infected Anopheles mosquitoes generally display increase attraction, biting and feeding rate 6-10. Interestingly, these changes are often concomitant with the presence of transmissible stages of the pathogen and may contribute to increase the number of contacts between human hosts and infectious vectors 11. These effects may lead to substantial epidemiological consequences, with transmission rates of mosquito borne pathogens being potentially much higher than expected 12. On the other hand, infection by malaria parasites may induce fitness costs on mosquitoes, reducing their survival. This can be especially true when infection is associated with other biotic and abiotic stresses 13-15. Consequently, all the behavioral and physiological changes associated with infection could directly impact the efficacy of control means. To date, conventional control tools mostly rely on the use of insecticide-treated nets (ITNs), although their efficacy could be threatened by the increase of insecticide resistance mechanisms in mosquito populations 16. Besides, repellents such as DEET (N, N-diethyl-3-methylbenzamide) offer a great potential both in cutaneous

Chemical signal is in the blend: bases of plant-pollinator encounter in a highly specialized interaction.

Abstract: In several highly specialized plant-insect interactions, scent-mediated specificity of pollinator attraction is directed by the emission and detection of volatile organic compounds (VOCs). Although some plants engaged in such interactions emit singular compounds, others emit mixtures of VOCs commonly emitted by plants. We investigated the chemical ecological bases of host plant recognition in the nursery pollination mutualism between the dioecious Ficus carica and its specific pollinator Blastophaga psenes. Using Y-tube olfactometer tests, we show that B. psenes females are attracted by VOCs of receptive figs of both sexes and do not exhibit preference for VOCs of either male or female figs. Electrophysiological tests and chemical analysis revealed that of all the VOCs emitted by receptive figs, only five were found to be active on female antennae. Behavioural tests show that, in contrast to VOCs presented alone, only a blend with a particular proportion of four of these VOCs is as attractive as the odour of receptive figs, and that if there is a very small change in this blend proportion, the pollinator is no longer attracted. This study revealed that in highly specialized mutualistic interactions specificity could be mediated by a particular blend of common compounds emitted by plants.

Targeting the progression of chronic kidney disease

Abstract: Chronic kidney disease (CKD) is a devastating condition that is reaching epidemic levels owing to the increasing prevalence of diabetes mellitus, hypertension and obesity, as well as ageing of the population. Regardless of the underlying aetiology, CKD is slowly progressive and leads to irreversible nephron loss, end-stage renal disease and/or premature death. Factors that contribute to CKD progression include parenchymal cell loss, chronic inflammation, fibrosis and reduced regenerative capacity of the kidney. Current therapies have limited effectiveness and only delay disease progression, underscoring the need to develop novel therapeutic approaches to either stop or reverse progression. Preclinical studies have identified several approaches that reduce fibrosis in experimental models, including targeting cytokines, transcription factors, developmental and signalling pathways and epigenetic modulators, particularly microRNAs. Some of these nephroprotective strategies are now being tested in clinical trials. Lessons learned from the failure of clinical studies of transforming growth factor β1 (TGFβ1) blockade underscore the need for alternative approaches to CKD therapy, as strategies that target a single pathogenic process may result in unexpected negative effects on simultaneously occurring processes. Additional promising avenues include preventing tubular cell injury and anti-fibrotic therapies that target activated myofibroblasts, the main collagen-producing cells. Here, the authors review drivers of fibrogenesis, including epithelial cell injury, inflammation, regeneration pathways and factors that promote the AKI-to-CKD transition. They discuss direct targeting of fibrotic pathways and therapeutic approaches that have reportedly decreased kidney fibrosis in preclinical and/or clinical studies.

Analysis of SARS-CoV-2 RNA-dependent RNA polymerase as a potential therapeutic drug target using a computational approach.

Abstract: The Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) outbreak originating in Wuhan, China, has raised global health concerns and the pandemic has now been reported on all inhabited continents Hitherto, no antiviral drug is available to combat this viral outbreak Keeping in mind the urgency of the situation, the current study was designed to devise new strategies for drug discovery and/or repositioning against SARS-CoV-2 In the current study, RNA-dependent RNA polymerase (RdRp), which regulates viral replication, is proposed as a potential therapeutic target to inhibit viral infection Evolutionary studies of whole-genome sequences of SARS-CoV-2 represent high similarity (> 90%) with other SARS viruses Targeting the RdRp active sites, ASP760 and ASP761, by antiviral drugs could be a potential therapeutic option for inhibition of coronavirus RdRp, and thus viral replication Target-based virtual screening and molecular docking results show that the antiviral Galidesivir and its structurally similar compounds have shown promise against SARS-CoV-2 The anti-polymerase drugs predicted here—CID123624208 and CID11687749—may be considered for in vitro and in vivo clinical trials

Reverse vaccinology assisted designing of multiepitope-based subunit vaccine against SARS-CoV-2.

Abstract: Coronavirus disease 2019 (COVID-19) linked with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause severe illness and life-threatening pneumonia in humans. The current COVID-19 pandemic demands an effective vaccine to acquire protection against the infection. Therefore, the present study was aimed to design a multiepitope-based subunit vaccine (MESV) against COVID-19. Structural proteins (Surface glycoprotein, Envelope protein, and Membrane glycoprotein) of SARS-CoV-2 are responsible for its prime functions. Sequences of proteins were downloaded from GenBank and several immunoinformatics coupled with computational approaches were employed to forecast B- and T- cell epitopes from the SARS-CoV-2 highly antigenic structural proteins to design an effective MESV. Predicted epitopes suggested high antigenicity, conserveness, substantial interactions with the human leukocyte antigen (HLA) binding alleles, and collective global population coverage of 88.40%. Taken together, 276 amino acids long MESV was designed by connecting 3 cytotoxic T lymphocytes (CTL), 6 helper T lymphocyte (HTL) and 4 B-cell epitopes with suitable adjuvant and linkers. The MESV construct was non-allergenic, stable, and highly antigenic. Molecular docking showed a stable and high binding affinity of MESV with human pathogenic toll-like receptors-3 (TLR3). Furthermore, in silico immune simulation revealed significant immunogenic response of MESV. Finally, MEV codons were optimized for its in silico cloning into the Escherichia coli K-12 system, to ensure its increased expression. The MESV developed in this study is capable of generating immune response against COVID-19. Therefore, if designed MESV further investigated experimentally, it would be an effective vaccine candidate against SARS-CoV-2 to control and prevent COVID-19.