Search Results (76)

A virome survey of banana plantations and their surrounding plants was carried out at nation-wide level in Malawi using virion associated nucleic acids (VANA) high throughput sequencing (HTS) on pooled samples and appropriate alien controls. In total, 366 plants were sequenced, and 23 plant virus species were detected, three species on banana (275 plants) and 20 species in surrounding plants (91 plants). Two putative novel virus species; ginger tymo-like virus and pepper derived totivirus were detected and confirmed by RT-PCR on ginger and pepper. Nine known virus species and detected a host plant was identified for two of them. No viral exchange between banana and surrounding plants was observed. Results from the VANA protocol, applied to pooled banana samples, were compared with previous targeted PCR results obtained from individual banana samples. HTS test detected better BanMMV than IC-(RT)-PCR on individual samples (better inclusivity) but detected with much lower sensitivity BBTV and BSV species, often with less than 10 reads per sample. Detection of novel and known viruses and new host plants calls for strengthened sanitory and phytosanitory measures within and beyond banana production systems. Our research confirms that HTS sensitivity depends on sampling, pooling protocol and targeted virus species. Full article

Background: The benzamide MMV030666 from MMV’s Malaria Box Project, the starting point of herein presented study, was initially tested against various Plasmodium falciparum strains as well as Gram-positive and Gram-negative bacteria. It exhibits multi-stage antiplasmodial potencies and lacks resistance development. Methods: The favorable structural features from previous series were kept while the influence of the N-Boc-piperazinyl substituent per se, as well as its ring position and its replacement by various heteroaromatic rings, was evaluated. Thus, this paper describes the preparation of the MMV030666-derived 4′-(piperazin-1-yl)benzanilides for the first time, exhibiting broad-spectrum activity not only against plasmodia but also various bacterial strains. Results: A series of insightful structure–activity relationships were determined. Furthermore, pharmacokinetic and physicochemical parameters of the new compounds were determined experimentally or in silico. Drug-likeliness according to Lipinski’s rules was calculated as well. Conclusions: A diarylthioether derivative of the lead compound was promisingly active against P. falciparum and exhibited broad-spectrum antibacterial activity against Gram-positive as well as Gram-negative bacteria. It is considered for testing against multi-resistant bacterial strains and in vivo studies. Full article

To tackle the challenge of enhancing moving target detection performance in environments characterized by small sample sizes and non-uniformity, methods rooted in sparse signal reconstruction have been incorporated into Space-Time Adaptive Processing (STAP) algorithms. Given the prominent sparse nature of clutter spectra in the angle-Doppler domain, adopting sparse recovery algorithms has proven to be a feasible approach for accurately estimating high-resolution spatio-temporal two-dimensional clutter spectra. Sparse Bayesian Learning (SBL) is a pivotal tool in sparse signal reconstruction and has been previously utilized, yet it has demonstrated limited success in enhancing sparsity, resulting in insufficient robustness in local fitting. To significantly improve sparsity, this paper introduces a hierarchical Bayesian prior framework and derives iterative parameter update formulas through variational inference techniques. However, this algorithm encounters significant computational hurdles during the parameter update process. To overcome this obstacle, the paper proposes an enhanced Variational Bayesian Inference (VBI) method that leverages prior information on the rank of the temporal clutter covariance matrix to refine the parameter update formulas, thereby significantly reducing computational complexity. Furthermore, this method fully exploits the joint sparsity of the Multiple Measurement Vector (MMV) model to achieve greater sparsity without compromising accuracy, and employs a first-order Taylor expansion to eliminate grid mismatch in the dictionary. The research presented in this paper enhances the moving target detection capabilities of STAP algorithms in complex environments and provides new perspectives and methodologies for the application of sparse signal reconstruction in related fields. Full article

Chagas disease, caused by the protozoan Trypanosoma cruzi, affects millions globally, with limited treatment options available. Current therapies, such as benznidazole and nifurtimox, present challenges, including their toxicity, side effects, and inefficacy in the chronic phase. This study explores the potential of drug repurposing as a strategy to identify new treatments for T. cruzi, focusing on compounds from the Medicines for Malaria Venture (MMV) COVID Box. An initial screening of 160 compounds identified eight with trypanocidal activity, with almitrine and bortezomib showing the highest efficacy. Both compounds demonstrated significant activity against the epimastigote and amastigote stages of the parasite and showed no cytotoxicity in murine macrophage cells. Key features of programmed cell death (PCD), such as chromatin condensation, mitochondrial membrane potential disruption, and reactive oxygen species accumulation, were observed in T. cruzi treated with these compounds. The potential to induce controlled cell death of these two compounds in T. cruzi suggests they are promising candidates for further research. This study reinforces drug repurposing as a viable approach to discovering novel treatments for neglected tropical diseases like Chagas disease. Full article

Sida mottle virus (SiMoV) and Sida micrantha mosaic virus (SiMMV) are major Brazilian begomoviruses (Geminiviridae). However, the range of DNA–A identity of isolates of these viruses (81–100%) is not in agreement with the current criteria for Begomovirus species demarcation (<91%). To clarify this putative classification problem, we performed a comprehensive set of molecular analyses with all 53 publicly available isolates (with complete DNA–A genomes) designated as either SiMoV or SiMMV (including novel isolates obtained herein from nationwide metagenomics-based studies). Two well-defined phylogenetic clusters were identified. The SiMMV complex (n = 47) comprises a wide range of strains (with a continuum variation of 88.8–100% identity) infecting members of five botanical families (Malvaceae, Solanaceae, Fabaceae, Oxalidaceae, and Passifloraceae). The SiMoV group now comprises eight isolates (90–100% identity) restricted to Malvaceae hosts, including one former reference SiMMV isolate (gb|NC_077711) and SP77 (gb|FN557522; erroneously named as “true SiMMV”). Iteron analyses of metagenomics-derived information allowed for the discovery of the missing DNA–B cognate of SiMoV (93.5% intergenic region identity), confirming its bipartite nature. Henceforth, the correct identification of SiMoV and SiMMV isolates will be a crucial element for effective classical and biotech resistance breeding of the viral host species. Full article

Tomato (Solanum lycopersicum L.), the second most important vegetable crop globally, faces a significant threat from various viral diseases. A newly emerging disease, characterised by distinctive shoestring symptoms on leaves and the development of unripe, small, and hard fruit, poses a serious challenge to tomato cultivation in India. An initial survey in an experimental field revealed more than 50% of the plants displayed symptoms of the shoestring disease, resulting in substantial reductions in fruit yield and quality. Transmission electron microscopy (TEM) and molecular analyses identified an isolate of the tomato mottle mosaic virus (ToMMV) in the affected plants. When the partially purified virus was mechanically inoculated into tomato cv. Pusa Ruby plants, it reproduced the characteristic shoestring symptoms, confirming its causal relationship with the disease. Notably, the present shoestring isolate of ToMMV (ToMMV-Tss) was found to induce similar shoestring symptoms in most of the major commercial tomato varieties when inoculated under controlled experimental conditions in the glasshouse, indicating its aggressive nature. Host range studies demonstrated that the ToMMV-Tss can infect several solanaceous species, while cucurbitaceous hosts remained unaffected. Moreover, the virus was found to be seed-transmissible, with a small percentage of seedlings from infected plants displaying symptoms. These findings underscore the significant impact of ToMMV on tomato production in India and emphasise the need for reliable diagnostic tools and effective management strategies to curb the spread and mitigate the impact of this virus on commercial tomato cultivation. Full article

Human schistosomiasis, caused by the Schistosoma trematode, is a neglected parasitic disease affecting over 250 million people worldwide. There is no vaccine, and the single available drug is threatened by drug resistance. This study presents a computational approach to designing multiepitope vaccines (MEVs) targeting the cercarial (CMEV) and schistosomular (SMEV) stages of schistosomes, and identifies potential schistosomicidal compounds from the Medicine for Malaria Ventures (MMV) and SuperNatural Database (SND) libraries. The designed vaccines (CMEV and SMEV) are engineered to provoke robust immune responses by incorporating a blend of T- and B-cell epitopes. Structural and immunoinformatics evaluations predicted robust interactions of CMEV and SMEV with key immune receptors and prolonged immune responses. In addition, molecular docking identified several compounds from the MMV and SND libraries with strong binding affinities to vital Schistosoma cathepsin proteases, indicating their potential as schistosomicidal agents. Our findings contribute to the potential development of effective vaccines and drugs against schistosomiasis. Full article

The objective of this work was to evaluate the properties of beverages formulated with Brazil nuts (Bertholletia excelsa Bonpl) and bocaiuva almonds (Acrocomia aculeata (Jacq.) Lodd. Ex Mart.). Five beverages were developed with Brazil nut, bocaiuva almond, and water (m/m/v), as follows: (i) NB, nut:water, 1:10; (ii) AB, almond:water, 1:10; (iii) NAB1, 1:0.1:10, nut:almond:water; (iv) NAB5, nut:almond:water, 1:0.5:10; and (v) NAB10, nut:almond:water, 1:1:10. The physicochemical, chemical, technological, and microbiological parameters were evaluated. After heat treatment (HT) and enrichment with minerals, the beverages that demonstrated stability in these characteristics were tested in a biological assay. The physical and biochemical parameters of male Wistar rats were evaluated after administering beverages for 28 days. HT decreased the total phenolic content and the antioxidant activity; however, it guaranteed microbiological safety. Mineral supplementation changed the colors and increased the pH values of the beverages. After the beverages were administered, the Wistar rats in the (i) NB group showed decreases in retroperitoneal adipose tissue, total cholesterol, and triglycerides; (ii) those in the AB group exhibited decreased triglycerides contents; and (iii) those in the NAB10-group presented decreased liver weights. The beverages evaluated in this study demonstrate a protective effect against risk factors such as fat accumulation in the liver, retroperitoneal adipose tissue, and hypercholesterolemia. Full article

Antimicrobial resistance (AMR) has emerged as a significant threat to public health, particularly in infections caused by critically important Gram-negative bacteria. The development of novel antibiotics has its limitations, and therefore it is crucial to explore alternative strategies to effectively combat infections with resistant pathogens. In this context, the present study investigated the antibacterial potency of 560 compounds against the multidrug-resistant (MDR) strains of Klebsiella pneumoniae and Serratia marcescens. The evaluated compounds were selected from the Pandemic Response Box (PRB) and COVID Box (CB) and subjected to assays to determine the inhibitory concentration (IC), minimum bactericidal concentration (MBC), and biofilm formation. Further, the effects of these compounds on membrane integrity were assessed through protein quantification. Several of the evaluated compounds, including fusidic acid, MMV1580853, and MMV1634399, exhibited a significant reduction in biofilm formation and growth in K. pneumoniae. Trimethoprim exhibited potential against S. marcescens. The IC values of the compounds indicated significant microbial growth inhibition at various concentrations. These findings underscore the potency of the existing antibiotics and novel compounds in combating the MDR strains of bacteria. The importance of reconsidering the known antibiotics and utilizing drug repositioning strategies to address the increasing risk of AMR is highlighted. Full article

The open-source drug library, namely, MMV Pandemic Response Box, contains 153 antiviral agents, a chemically and pharmacologically diverse mixture of early-stage, emerging anti-infective scaffolds, and mature compounds currently undergoing clinical development. Hence, the Pandemic Response Box might contain compounds that bind and interfere with target molecules or cellular pathways that are conserved or shared among the closely related viruses with enterovirus A71 (EV-A71). This study aimed to screen antiviral agents included in the Pandemic Response Box for repurposing to anti-EV-A71 activity and investigate the inhibitory effects of the compounds on viral replication. The compounds’ cytotoxicity and ability to rescue infected cells were determined by % cell survival using an SRB assay. The hit compounds were verified for anti-EV-A71 activity by virus reduction assays for viral RNA copy numbers, viral protein synthesis, and mature particle production using qRT-PCR, Western blot analysis, and CCID₅₀ assay, respectively. It was found that some of the hit compounds could reduce EV-A71 genome replication and protein synthesis. D-D7 (2-pyridone-containing human rhinovirus 3C protease inhibitor) exhibited the highest anti-EV-A71 activity. Even though D-D7 has been originally indicated as a polyprotein processing inhibitor of human rhinovirus 3C protease, it could be repurposed as an anti-EV-A71 agent. Full article

Objectives: Eumycetoma is a neglected tropical disease (NTD) characterized by subcutaneous lesions and the formation of grains. Attempts to treat eumycetoma involve a combination of antifungal treatment and surgery, although the outcome is frequently disappointing. Therefore, there is a need to identify novel antifungal drugs to treat eumycetoma. In this respect, Medicines for Malaria Venture (MMV) has assembled libraries of compounds for researchers to use in drug discovery research against NTD. Therefore, we screened two MMVOpen compound libraries to identify novel leads for eumycetoma. Methods: A total of 400 compounds from the COVID Box and the Global Health Priority Box were screened in vitro at 100 µM and 25 µM against the most common causative agents of eumycetoma, namely Madurella mycetomatis and Falciformispora senegalensis, and the resulting IC₅₀ and MIC₅₀ values were obtained. Compounds with an IC₅₀ < 8 µM were identified for possible in vivo efficacy studies using an M. mycetomatis grain model in Galleria mellonella larvae. Results: Out of the 400 compounds, 22 were able to inhibit both M. mycetomatis and F. senegalensis growth at 100 µM and 25 µM, with compounds MMV1593278, MMV020335, and MMV1804559 being selected for in vivo testing. Of these three, only the pyrazolopyrimidine derivative MMV1804559 was able to prolong the survival of M. mycetomatis-infected G. mellonella larvae. Furthermore, the grains in MMV1804559-treated larvae were significantly smaller compared to the PBS-treated group. Conclusion: MMV1804559 shows promising in vitro and in vivo activity against M. mycetomatis. Full article

This study investigates the in vitro activity of Nα-aroyl-N-aryl-phenylalanine amides (AAPs), previously identified as antimycobacterial RNA polymerase (RNAP) inhibitors, against a panel of 25 non-tuberculous mycobacteria (NTM). The compounds, including the hit compound MMV688845, were selected based on their structural diversity and previously described activity against mycobacteria. Bacterial strains, including the M. abscessus complex, M. avium complex, and other clinically relevant NTM, were cultured and subjected to growth inhibition assays. The results demonstrate significant activity against the most common NTM pathogens from the M. abscessus and M. avium complexes. Variations in activity were observed against other NTM species, with for instance M. ulcerans displaying high susceptibility and M. xenopi and M. simiae resistance to AAPs. Comparative analysis of RNAP β and β′ subunits across mycobacterial species revealed strain-specific polymorphisms, providing insights into differential compound susceptibility. While conservation of target structures was observed, differences in compound activity suggested influences beyond drug–target interactions. This study highlights the potential of AAPs as effective antimycobacterial agents and emphasizes the complex interplay between compound structure, bacterial genetics, and in vitro activity. Full article

Uncertainties and discrepant results in identifying crucial areas for emotional facial expression recognition may stem from the eye tracking data analysis methods used. Many studies employ parameters of analysis that predominantly prioritize the examination of the foveal vision angle, ignoring the potential influences of simultaneous parafoveal and peripheral information. To explore the possible underlying causes of these discrepancies, we investigated the role of the visual field aperture in emotional facial expression recognition with 163 volunteers randomly assigned to three groups: no visual restriction (NVR), parafoveal and foveal vision (PFFV), and foveal vision (FV). Employing eye tracking and gaze contingency, we collected visual inspection and judgment data over 30 frontal face images, equally distributed among five emotions. Raw eye tracking data underwent Eye Movements Metrics and Visualizations (EyeMMV) processing. Accordingly, the visual inspection time, number of fixations, and fixation duration increased with the visual field restriction. Nevertheless, the accuracy showed significant differences among the NVR/FV and PFFV/FV groups, despite there being no difference in NVR/PFFV. The findings underscore the impact of specific visual field areas on facial expression recognition, highlighting the importance of parafoveal vision. The results suggest that eye tracking data analysis methods should incorporate projection angles extending to at least the parafoveal level. Full article

For direction-of-arrival (DOA) estimation problems in a sparse domain, sparse Bayesian learning (SBL) is highly favored by researchers owing to its excellent estimation performance. However, traditional SBL-based methods always assign Gaussian priors to parameters to be solved, leading to moderate sparse signal recovery (SSR) effects. The reason is Gaussian priors play a similar role to $l_2$ regularization in sparsity constraint. Therefore, numerous methods are developed by adopting hierarchical priors that are used to perform better than Gaussian priors. However, these methods are in straitened circumstances when multiple measurement vector (MMV) data are adopted. On this basis, a block-sparse SBL method (named BSBL) is developed to handle DOA estimation problems in MMV models. The novelty of BSBL is the combination of hierarchical priors and block-sparse model originating from MMV data. Therefore, on the one hand, BSBL transfers the MMV model to a block-sparse model by vectorization so that Bayesian learning is directly performed, regardless of the prior independent assumption of different measurement vectors and the inconvenience caused by the solution of matrix form. On the other hand, BSBL inherited the advantage of hierarchical priors for better SSR ability. Despite the benefit, BSBL still has the disadvantage of relatively large computation complexity caused by high dimensional matrix operations. In view of this, two operations are implemented for low complexity. One is reducing the matrix dimension of BSBL by approximation, generating a method named BSBL-APPR, and the other is embedding the generalized approximate message passing (GAMB) technique into BSBL so as to decompose matrix operations into vector or scale operations, named BSBL-GAMP. Moreover, BSBL is able to suppress temporal correlation and handle wideband sources easily. Extensive simulation results are presented to prove the superiority of BSBL over other state-of-the-art algorithms. Full article

The study of geological CO₂ sequestration and its long-term implications are crucial for ensuring the safety and sustainability of carbon capture and storage (CCS) projects. This work presents a numerical reservoir modeling study to upscale CO₂ injection in the Eastern Illinois Basin to a cumulative value of 27 Mt within the next 20 years, adding one proposed Class VI injector well to the two already existing ones in this field. Along with the reservoir simulations that include the main CO₂ trapping mechanisms that ensure a minimum of a 100-year Area-of-Review containment, we describe a step-by-step approach to enhance measurement, monitoring, and verification (MMV) plans, starting from low-cost methods such as repeated 1D VSP in existing boreholes to 2D seismic surveys and higher-cost data acquisition techniques. Full article