Anti-dengue potential and mosquitocidal effect of marine green algae-stabilized Mn-doped superparamagnetic iron oxide nanoparticles (Mn-SPIONs): an eco-friendly approach.

Vector-borne diseases pose a significant public health challenge in economically disadvantaged nations. Malaria, dengue fever, chikungunya, Zika, yellow fever, Japanese encephalitis, and lymphatic filariasis are spread by mosquitoes. Consequently, the most effective method of preventing these diseases is to eliminate the mosquito population. Historically, the majority of control programs have depended on chemical pesticides, including organochlorines, organophosphates, carbamates, and pyrethroids. Synthetic insecticides used to eradicate pests have the potential to contaminate groundwater, surface water, beneficial soil organisms, and non-target species. Nanotechnology is an innovative technology that has the potential to be used in insect control with great precision. The goal of this study was to test the in vitro anti-dengue potential and mosquitocidal activity of Chaetomorpha aerea and C. aerea-synthesized Mn-doped superparamagnetic iron oxide nanoparticles (CA-Mn-SPIONs). The synthesis of CA-Mn-SPIONs using C. aerea extract was verified by the observable alteration in the colour of the reaction mixture, transitioning from a pale green colour to a brown. The study of UV-Vis spectra revealed absorbance peaks at approximately 290 nm, which can be attributed to the surface Plasmon resonance of the CA-Mn-SPIONs. The SEM, TEM, EDX, FTIR, vibrating sample magnetometry, and XRD analyses provided evidence that confirmed the presence of CA-Mn-SPIONs. In the present study, results revealed that C. aerea aqueous extract LC50 values against Ae. aegypti ranged from 222.942 (first instar larvae) to 349.877 ppm in bioassays (pupae). CA-Mn-SPIONs had LC50 ranging from 20.199 (first instar larvae) to 26.918 ppm (pupae). After treatment with 40 ppm CA-Mn-SPIONs and 500 ppm C. aerea extract in ovicidal tests, egg hatchability was lowered by 100%. Oviposition deterrence experiments showed that in Ae. aegypti, oviposition rates were lowered by more than 66% by 100 ppm of green algal extract and by more than 71% by 10 ppm of CA-Mn-SPIONs (oviposition activity index values were 0.50 and 0.55, respectively). Moreover, in vitro anti-dengue activity of CA-Mn-SPIONs has good anti-viral property against dengue viral cell lines. In addition, GC-MS analysis showed that 21 intriguing chemicals were discovered. Two significant phytoconstituents in the methanol extract of C. aerea include butanoic acid and palmitic acid. These two substances were examined using an in silico methodology against the NS5 methyltransferase protein and demonstrated good glide scores and binding affinities. Finally, we looked into the morphological damage and fluorescent emission of third instar Ae. aegypti larvae treated with CA-Mn-SPIONs. Fluorescent emission is consistent with ROS formation of CA-Mn-SPIONs against Ae. aegypti larvae. The present study determines that the key variables for the successful development of new insecticidal agents are rooted in the eco-compatibility and the provision of alternative tool for the pesticide manufacturing sector.

Casearia tomentosa fruit extracts exposed larvicidal activity and morphological alterations in Culex quinquefasciatus and Aedes albopictus under in vitro and semi field conditions.

Mosquitoes are notorious insects that transmit a wide range of infectious diseases, including zika, malaria, chikungunya, filariasis, and dengue. The overuse and incorrect application of synthetic pesticides to control mosquitoes has resulted in resistance development and environmental contamination, both of which have had a negative impact on human health. To address this issue, the larvicidal and pupicidal potential of acetone extract from Casearia tomentosa fruits was investigated. The extract was evaluated in a lab setting against all larval instars and pupa of Culex quinquefasciatus and Aedes albopictus, as well as against third instar larvae in a semi-field condition. Purified compounds through TLC were also tested against 3rd instar larvae of both mosquito and non-target organisms. The FT-IR and GC-MS analyses were used to characterise the extract. Morphological aberration caused by the acetone extract was observed using FESEM. The anal gills and respiratory siphon of both mosquitoes showed significant deformation from their normal state. 100 ppm was found to cause 100% larval mortality at 24 h of exposure in case of Cx. quinquefasciatus and at 72 h of exposure in Ae. albopictus larvae. After 72 h of exposure under in vitro conditions, the extract demonstrated considerable larvicidal activity with LC50 values of 38.33 and 47.56 against 3rd instar larvae of Culex quinquefasciatus and Aedes albopictus, respectively. The acetone extract can be considered as a highly effective mosquito larvicidal agent that is safe for the environment.

Atranorin inhibits Zika virus infection in human glioblastoma cell line SNB-19 via targeting Zika virus envelope protein.

BACKGROUND: Zika virus (ZIKV) is a single-stranded RNA flavivirus transmitted by mosquitoes. Its infection is associated with neurological complications such as neonatal microcephaly and adult Guillain-Barré syndrome, posing a serious threat to the health of people worldwide. Therefore, there is an urgent need to develop effective anti-ZIKV drugs. Atranorin is a lichen secondary metabolite with a wide range of biological activities, including anti-inflammatory, antibacterial and antioxidant, etc. However, the antiviral activity of atranorin and underlying mechanism has not been fully elucidated. PURPOSE: We aimed to determine the anti-ZIKV activity of atranorin in human glioma cell line SNB-19 and investigate the potential mechanism from the perspective of viral life cycle and the host cell functions. METHODS: We first established ZIKV-infected human glioma cells (SNB-19) model and used Western Blot, RT-qPCR, immunofluorescence, fluorescence-activated cell sorting (FACS) and plaque assay to evaluate the anti-ZIKV activity of atranorin. Then we assessed the regulation effect of atranorin on ZIKV induced IFN signal pathway activation by RT-qPCR. Afterward, we introduced time-of-addition assay, viral adsorption assay, viral internalization assay and transferrin uptake assay to define which step of ZIKV lifecycle is influenced by atranorin. Finally, we performed virus infectivity assay, molecular docking and thermal shift assay to uncover the target protein of atranorin on ZIKV. RESULTS: Our study showed that atranorin could protect SNB-19 cells from ZIKV infection, as evidenced by inhibited viral protein expression and progeny virus yield. Meanwhile, atranorin attenuated the activation of IFN signal pathway and downstream inflammatory response that induced by ZIKV infection. The results of time-of-addition assay indicated that atranorin acted primarily by disturbing the viral entry process. After ruling out the effect of atranorin on AXL receptor tyrosine kinase (AXL) dependent virus adsorption and clathrin-mediated endocytosis, we confirmed that atranorin directly targeted the viral envelope protein and lowered ZIKV infectivity by thermal shift assay and virus infectivity assay respectively. CONCLUSION: We found atranorin inhibits ZIKV infection in SNB-19 cells via targeting ZIKV envelope protein. Our study provided an experimental basis for the further development of atranorin and a reference for antiviral drug discovery from natural resources.

Identification, characterization and quantification of xanthones from Fridericia formosa leaves extract with antiviral activity.

Fridericia formosa (Bureau) L.G. Lohmann (Bignonaceae) is a neotropical liana species found in the Cerrado biome in Brazil. It has been of great interest to the scientific community due to its potential as a source of new antivirals, including xanthones derived from mangiferin. In this context, the present study aimed to characterize and quantify the xanthones present in the ethanol extract of this species using high performance liquid chromatography. Additionally, the antiviral activity against Chikungunya, Zika, and Mayaro viruses was evaluated. The chromatographic analyses partially identified twenty-six xanthones, among which only fourteen had already been described in the literature. The xanthones mangiferin, 2'-O-trans-caffeoylmangiferin, and 2'-O-trans-coumaroylmangiferin, are present in higher quantities in the extract, at concentrations of 9.65%, 10.68%, and 3.41% w/w, respectively. In antiviral assays, the extract inhibited the multiplication cycle only for the Mayaro virus with a CE50 of 36.1 µg/mL. Among the isolated xanthones, 2'-O-trans-coumaroylmangiferin and 2'-O-trans-cinnamoylmangiferin inhibited the viral cytopathic effect with CE50 values of 180.6 and 149.4 µg/mL, respectively. Therefore, the extract from F. formosa leaves, which has a high content of xanthones, has antiviral potential and can be a source of new mangiferin derivatives.

Exploring the antiviral potential of justicidin B and four glycosylated lignans from Phyllanthus brasiliensis against Zika virus: A promising pharmacological approach.

BACKGROUND: Zika virus (ZIKV) is an emerging arbovirus that in recent years has been associated with cases of severe neurological disorders, such as microcephaly in newborns and Guillain-Barré syndrome in adults. As there is no vaccine or treatment, the search for new therapeutic targets is of great relevance. In this sense, plants are extremely rich sources for the discovery of new bioactive compounds and the species Phyllanthus brasiliensis (native to the Amazon region) remains unexplored. PURPOSE: To investigate the potential antiviral activity of compounds isolated from P. brasiliensis leaves against ZIKV infection. METHODS: In vitro antiviral assays were performed with justicidin B (a lignan) and four glycosylated lignans (tuberculatin, phyllanthostatin A, 5-O-ß-d-glucopyranosyljusticidin B, and cleistanthin B) against ZIKV in Vero cells. MTT colorimetric assay was used to assess cell viability and plaque forming unit assay to quantify viral load. In addition, for justicidin B, tests were performed to investigate the mechanism of action (virucidal, adsorption, internalization, post-infection). RESULTS: The isolated compounds showed potent anti-ZIKV activities and high selectivity indexes. Moreover, justicidin B, tuberculatin, and phyllanthostatin A completely reduced the viral load in at least one of the concentrations evaluated. Among them, justicidin B stood out as the main active, and further investigation revealed that justicidin B exerts its antiviral effect during post-infection stages, resulting in a remarkable 99.9 % reduction in viral load when treatment was initiated 24 h after infection. CONCLUSION: Our findings suggest that justicidin B inhibits endosomal internalization and acidification, effectively interrupting the viral multiplication cycle. Therefore, the findings shed light on the promising potential of isolated compounds isolated from P. brasiliensis, especially justicidin B, which could contribute to the drug development and treatments for Zika virus infections.

Biological evaluation of 1,3-benzodioxole acids points to 3,4-(methylenedioxy) cinnamic acid as a potential larvicide against Aedes aegypti (Diptera: Culicidae).

Aedes aegypti serves as the primary vector for viruses like dengue, Chikungunya, Zika, and yellow fever, posing a significant public health challenge in Brazil. Given the absence of approved vaccines for these diseases, effective mosquito control becomes paramount in preventing outbreaks. However, currently available chemical insecticides face issues related to toxicity and the emergence of resistance, necessitating the exploration of new active compounds. Drawing inspiration from natural products, we identified the 1,3-benzodioxole group as a key pharmacophore associated with insecticidal activity. Therefore, this study aimed to synthesize and assess the larvicidal activity of 1,3-benzodioxole acids against Ae. aegypti, as well as their toxicity in mammals. Among the compounds evaluated, 3,4-(methylenedioxy) cinnamic acid (compound 4) demonstrated larvicidal activity. It exhibited LC50 and LC90 values of 28.9 ± 5.6 and 162.7 ± 26.2 µM, respectively, after 24 h of exposure. For reference, the positive control, temephos, displayed both LC50 and LC90 values below 10.94 µM. These findings underline the significance of the 3,4-methylenedioxy substituent on the aromatic ring and the presence of a double bond in the aliphatic chain for biological activity. Furthermore, compound 4 exhibited no cytotoxicity towards human peripheral blood mononuclear cells, even at concentrations up to 5200 µM. Lastly, in mice treated with 2000 mg kg-1, compound 4 showed mild behavioral effects and displayed no structural signs of toxicity in vital organs such as the kidney, liver, spleen, and lungs.

Insecticidal activity of essential oil from leaves of Eugenia stipitata McVaugh against Aedes aegypti.

Aedes aegypti, a mosquito, is responsible for the spread of many diseases, including dengue, zika, and chikungunya. However, due to this mosquito's developed resistance to conventional pesticides, effectively controlling it has proven to be challenging. This study aimed to evaluate the insecticidal potential of the essential oil from the leaves of Eugenia stipitata against Ae. aegypti, offering a natural and sustainable alternative for mosquito control. Tests were conducted using third-stage larvae to evaluate larvicidal activity and pupae collected up to 14 h after transformation to investigate pupicidal activity. Throughout the bioassays, the organisms were exposed to various essential oil concentrations. The findings demonstrated that the essential oil of E. stipitata exhibited larvicidal action, resulting in 100% larval mortality after 24 h and an LC50 value of 0.34 mg/mL. The effectiveness of essential oil as a pupicidal agent was also demonstrated by its LC50 value of 2.33 mg/mL and 100% larval mortality in 24 h. It can be concluded that the essential oil of E. stipitata holds promise as a natural pest control agent. Its use may reduce the reliance on conventional chemical pesticides, providing a more sustainable and effective strategy to combat diseases spread by mosquitoes.

Native fungi from Amazon with potential for control of Aedes aegypti L. (Diptera: Culicidae).

Aedes aegypti L. (Diptera: Culicidae) is the main transmitter of pathogens that cause human diseases, including dengue, chikungunya, zika and yellow fever. Faced with this problem, this study aims to select fungi with entomopathogenic potential against Ae. aegypti and develop formulations that optimize the control action of entomopathogenic fungi in the semi-field condition. 23 fungal strains native from Amazon were inoculated in Potato-Dextrose-Agar (PDA) culture medium for 14 days and then transferred by scraping to tubes containing 0.9% NaCl solution. To obtain the larvae, eggs were collected using traps in peridomestic environments for 7 days. 20 larvae of Ae. aegypti in 125 mL erlenmeyers containing 20 mL of conidial suspension at a concentration of 1x106 conidia/mL for initial selection and 1×104, 1×105, 1×106 and 1×107 conidia/mL for determination of LC50. Mortality was checked every 24 h for 5 days. The three fungi with the best virulence rates were identified using molecular techniques. The compatibility between fungi at a concentration of 1×106 conidia/mL and oily adjuvants, mineral oil and vegetable oil (andiroba, chestnut and copaiba) at concentrations of 0.1, 0.5 and 1% was evaluated. The germination capacity of 100 conidia per treatment was evaluated after incubation at 28 ºC for 24 h. To evaluate the entomopathogenic potential of the fungal formulations, conidial suspensions (1×106 conidia/mL) were added with 0.1% mineral and vegetable oil. The treatments were submitted to laboratory and semi-field conditions and mortality was verified every 24 h for 5 days. Beauveria sp. (4,458) (LC50 = 8.66× 103), Metarhizium anisopliae (4,420) (LC50 = 5.48×104) and M. anisopliae (4,910) (LC50 = 1.13×105) were significantly more effective in the larval control of Ae. aegypti, in relation to the other fungal morphospecies evaluated. Mineral oil was better compatible in all treatments evaluated. Beauveria sp. (4,458) was considerably less virulent under semi-field conditions. M. anisopliae (4,910) formulated with mineral oil increased larval mortality to 100% on the 4th day in the laboratory and on the 5th day in the semi-field. Fungal formulations developed from native Amazonian isolates represent a promising tool for the development of strategies to control Ae. aegypti.

Use of micro and macroalgae extracts for the control of vector mosquitoes.

Mosquitoes are one of the most dangerous vectors of human diseases such as malaria, dengue, chikungunya, and Zika virus. Controlling these vectors is a challenging responsibility for public health authorities worldwide. In recent years, the use of products derived from living organisms has emerged as a promising approach for mosquito control. Among these living organisms, algae are of great interest due to their larvicidal properties. Some algal species provide nutritious food for larvae, while others produce allelochemicals that are toxic to mosquito larvae. In this article, we reviewed the existing literature on the larvicidal potential of extracts of micro- and macroalgae, transgenic microalgae, and nanoparticles of algae on mosquitoes and their underlying mechanisms. The results of many publications show that the toxic effects of micro- and macroalgae on mosquitoes vary according to the type of extraction, solvents, mosquito species, exposure time, larval stage, and algal components. A few studies suggest that the components of algae that have toxic effects on mosquitoes show through synergistic interaction between components, inhibition of feeding, damage to gut membrane cells, and inhibition of digestive and detoxification enzymes. In conclusion, algae extracts, transgenic microalgae, and nanoparticles of algae have shown significant larvicidal activity against mosquitoes, making them potential candidates for the development of new mosquito control products.

Untargeted-based metabolomics analysis and in vitro/in silico antiviral activity of extracts from Phyllanthus brasiliensis (Aubl.) Poir.

INTRODUCTION: This study describes the molecular profile and the potential antiviral activity of extracts from Phyllanthus brasiliensis, a plant widely found in the Brazilian Amazon. The research aims to shed light on the potential use of this species as a natural antiviral agent. METHODS: The extracts were analysed using liquid chromatography-mass spectrometry (LC-MS) system, a potent analytical technique to discover drug candidates. In the meantime, in vitro antiviral assays were performed against Mayaro, Oropouche, Chikungunya, and Zika viruses. In addition, the antiviral activity of annotated compounds was predicted by in silico methods. RESULTS: Overall, 44 compounds were annotated in this study. The results revealed that P. brasiliensis has a high content of fatty acids, flavones, flavan-3-ols, and lignans. Furthermore, in vitro assays revealed potent antiviral activity against different arboviruses, especially lignan-rich extracts against Zika virus (ZIKV), as follows: methanolic extract from bark (MEB) [effective concentration for 50% of the cells (EC50 ) = 0.80 µg/mL, selectivity index (SI) = 377.59], methanolic extract from the leaf (MEL) (EC50 = 0.84 µg/mL, SI = 297.62), and hydroalcoholic extract from the leaf (HEL) (EC50 = 1.36 µg/mL, SI = 735.29). These results were supported by interesting in silico prediction, where tuberculatin (a lignan) showed a high antiviral activity score. CONCLUSIONS: Phyllanthus brasiliensis extracts contain metabolites that could be a new kick-off point for the discovery of candidates for antiviral drug development, with lignans becoming a promising trend for further virology research.

Identification of alpha-linolenic acid as a broad-spectrum antiviral against zika, dengue, herpes simplex, influenza virus and SARS-CoV-2 infection.

Zika virus (ZIKV) has garnered global attention due to its association with severe congenital defects including microcephaly. However, there are no licensed vaccines or drugs against ZIKV infection. Pregnant women have the greatest need for treatment, making drug safety crucial. Alpha-linolenic acid (ALA), a polyunsaturated ω-3 fatty acid, has been used as a health-care product and dietary supplement due to its potential medicinal properties. Here, we demonstrated that ALA inhibits ZIKV infection in cells without loss of cell viability. Time-of-addition assay revealed that ALA interrupts the binding, adsorption, and entry stages of ZIKV replication cycle. The mechanism is probably that ALA disrupts membrane integrity of the virions to release ZIKV RNA, inhibiting viral infectivity. Further examination revealed that ALA inhibited DENV-2, HSV-1, influenza virus and SARS-CoV-2 infection dose-dependently. ALA is a promising broad-spectrum antiviral agent.

Different outcomes of neonatal and adult Zika virus infection on startle reflex and prepulse inhibition in mice.

Zika virus (ZIKV) infection causes severe neurological consequences in both gestationally-exposed infants and adults. Sensorial gating deficits strongly correlate to the motor, sensorial and cognitive impairments observed in ZIKV-infected patients. However, no startle response or prepulse inhibition (PPI) assessment has been made in patients or animal models. In this study, we identified different outcomes according to the age of infection and sex in mice: neonatally infected animals presented an increase in PPI and delayed startle latency. However, adult-infected male mice presented lower startle amplitude, while a PPI impairment was observed 14 days after infection in both sexes. Our data further the understanding of the functional impacts of ZIKV on the developing and mature nervous system, which could help explain other behavioral and cognitive alterations caused by the virus. With this study, we support the startle reflex testing in ZIKV-exposed patients, especially infants, allowing for early detection of functional neuromotor damage and early intervention.

Travel-Related Diagnoses Among U.S. Nonmigrant Travelers or Migrants Presenting to U.S. GeoSentinel Sites - GeoSentinel Network, 2012-2021.

Problem/Condition: During 2012-2021, the volume of international travel reached record highs and lows. This period also was marked by the emergence or large outbreaks of multiple infectious diseases (e.g., Zika virus, yellow fever, and COVID-19). Over time, the growing ease and increased frequency of travel has resulted in the unprecedented global spread of infectious diseases. Detecting infectious diseases and other diagnoses among travelers can serve as sentinel surveillance for new or emerging pathogens and provide information to improve case identification, clinical management, and public health prevention and response. Reporting Period: 2012-2021. Description of System: Established in 1995, the GeoSentinel Network (GeoSentinel), a collaboration between CDC and the International Society of Travel Medicine, is a global, clinical-care-based surveillance and research network of travel and tropical medicine sites that monitors infectious diseases and other adverse health events that affect international travelers. GeoSentinel comprises 71 sites in 29 countries where clinicians diagnose illnesses and collect demographic, clinical, and travel-related information about diseases and illnesses acquired during travel using a standardized report form. Data are collected electronically via a secure CDC database, and daily reports are generated for assistance in detecting sentinel events (i.e., unusual patterns or clusters of disease). GeoSentinel sites collaborate to report disease or population-specific findings through retrospective database analyses and the collection of supplemental data to fill specific knowledge gaps. GeoSentinel also serves as a communications network by using internal notifications, ProMed alerts, and peer-reviewed publications to alert clinicians and public health professionals about global outbreaks and events that might affect travelers. This report summarizes data from 20 U.S. GeoSentinel sites and reports on the detection of three worldwide events that demonstrate GeoSentinel's notification capability. Results: During 2012-2021, data were collected by all GeoSentinel sites on approximately 200,000 patients who had approximately 244,000 confirmed or probable travel-related diagnoses. Twenty GeoSentinel sites from the United States contributed records during the 10-year surveillance period, submitting data on 18,336 patients, of which 17,389 lived in the United States and were evaluated by a clinician at a U.S. site after travel. Of those patients, 7,530 (43.3%) were recent migrants to the United States, and 9,859 (56.7%) were returning nonmigrant travelers.Among the recent migrants to the United States, the median age was 28.5 years (range = <19 years to 93 years); 47.3% were female, and 6.0% were U.S. citizens. A majority (89.8%) were seen as outpatients, and among 4,672 migrants with information available, 4,148 (88.8%) did not receive pretravel health information. Of 13,986 diagnoses among migrants, the most frequent were vitamin D deficiency (20.2%), Blastocystis (10.9%), and latent tuberculosis (10.3%). Malaria was diagnosed in 54 (<1%) migrants. Of the 26 migrants diagnosed with malaria for whom pretravel information was known, 88.5% did not receive pretravel health information. Before November 16, 2018, patients' reasons for travel, exposure country, and exposure region were not linked to an individual diagnosis. Thus, results of these data from January 1, 2012, to November 15, 2018 (early period), and from November 16, 2018, to December 31, 2021 (later period), are reported separately. During the early and later periods, the most frequent regions of exposure were Sub-Saharan Africa (22.7% and 26.2%, respectively), the Caribbean (21.3% and 8.4%, respectively), Central America (13.4% and 27.6%, respectively), and South East Asia (13.1% and 16.9%, respectively). Migrants with diagnosed malaria were most frequently exposed in Sub-Saharan Africa (89.3% and 100%, respectively).Among nonmigrant travelers returning to the United States, the median age was 37 years (range = <19 years to 96 years); 55.7% were female, 75.3% were born in the United States, and 89.4% were U.S. citizens. A majority (90.6%) were seen as outpatients, and of 8,967 nonmigrant travelers with available information, 5,878 (65.6%) did not receive pretravel health information. Of 11,987 diagnoses, the most frequent were related to the gastrointestinal system (5,173; 43.2%). The most frequent diagnoses among nonmigrant travelers were acute diarrhea (16.9%), viral syndrome (4.9%), and irritable bowel syndrome (4.1%).Malaria was diagnosed in 421 (3.5%) nonmigrant travelers. During the early (January 1, 2012, to November 15, 2018) and later (November 16, 2018, to December 31, 2021) periods, the most frequent reasons for travel among nonmigrant travelers were tourism (44.8% and 53.6%, respectively), travelers visiting friends and relatives (VFRs) (22.0% and 21.4%, respectively), business (13.4% and 12.3%, respectively), and missionary or humanitarian aid (13.1% and 6.2%, respectively). The most frequent regions of exposure for any diagnosis among nonmigrant travelers during the early and later period were Central America (19.2% and 17.3%, respectively), Sub-Saharan Africa (17.7% and 25.5%, respectively), the Caribbean (13.0% and 10.9%, respectively), and South East Asia (10.4% and 11.2%, respectively).Nonmigrant travelers who had malaria diagnosed were most frequently exposed in Sub-Saharan Africa (88.6% and 95.9% during the early and later period, respectively) and VFRs (70.3% and 57.9%, respectively). Among VFRs with malaria, a majority did not receive pretravel health information (70.2% and 83.3%, respectively) or take malaria chemoprophylaxis (88.3% and 100%, respectively). Interpretation: Among ill U.S. travelers evaluated at U.S. GeoSentinel sites after travel, the majority were nonmigrant travelers who most frequently received a gastrointestinal disease diagnosis, implying that persons from the United States traveling internationally might be exposed to contaminated food and water. Migrants most frequently received diagnoses of conditions such as vitamin D deficiency and latent tuberculosis, which might result from adverse circumstances before and during migration (e.g., malnutrition and food insecurity, limited access to adequate sanitation and hygiene, and crowded housing,). Malaria was diagnosed in both migrants and nonmigrant travelers, and only a limited number reported taking malaria chemoprophylaxis, which might be attributed to both barriers to acquiring pretravel health care (especially for VFRs) and lack of prevention practices (e.g., insect repellant use) during travel. The number of ill travelers evaluated by U.S. GeoSentinel sites after travel decreased in 2020 and 2021 compared with previous years because of the COVID-19 pandemic and associated travel restrictions. GeoSentinel detected limited cases of COVID-19 and did not detect any sentinel cases early in the pandemic because of the lack of global diagnostic testing capacity. Public Health Action: The findings in this report describe the scope of health-related conditions that migrants and returning nonmigrant travelers to the United States acquired, illustrating risk for acquiring illnesses during travel. In addition, certain travelers do not seek pretravel health care, even when traveling to areas in which high-risk, preventable diseases are endemic. Health care professionals can aid international travelers by providing evaluations and destination-specific advice.Health care professionals should both foster trust and enhance pretravel prevention messaging for VFRs, a group known to have a higher incidence of serious diseases after travel (e.g., malaria and enteric fever). Health care professionals should continue to advocate for medical care in underserved populations (e.g., VFRs and migrants) to prevent disease progression, reactivation, and potential spread to and within vulnerable populations. Because both travel and infectious diseases evolve, public health professionals should explore ways to enhance the detection of emerging diseases that might not be captured by current surveillance systems that are not site based.

Novel development of Lecanicillium lecanii-based granules as a platform against malarial vector Anopheles culicifacies.

Mosquitoes are infectious vectors for a wide range of pathogens and parasites thereby transmitting several diseases including malaria, dengue, Zika, Japanese encephalitis and chikungunya which pose a major public health concern. Mostly synthetic insecticides are usually applied as a primary control strategy to manage vector-borne diseases. However excessive and non-judicious usage of such chemically derived insecticides has led to serious environmental and health issues owing to their biomagnification ability and increased toxicity towards non-target organisms. In this context, many such bioactive compounds originating from entomopathogenic microbes serve as an alternative strategy and environmentally benign tool for vector control. In the present paper, the entomopathogenic fungus, Lecanicillium lecanii (LL) was processed to make the granules. Developed 4% LL granules have been characterized using the technique of Fourier transform infrared spectroscopy (FTIR) and scanning electron microscope (SEM). The developed formulation was also subjected to an accelerated temperature study at 40 °C and was found to be stable for 3 months. Further, GCMS of the L. lecanii was also performed to screen the potential biomolecules present. The developed formulation was found to be lethal against Anopheles culicifacies with an LC50 value of 11.836 µg/mL. The findings from SEM and histopathology also substantiated the mortality effects. Further, the SEM EDX (energy dispersive X-ray) studies revealed that the treated larvae have lower nitrogen content which is correlated to a lower level of chitin whereas the control ones has higher chitin content and healthy membranes. The developed LL granule formulation exhibited high toxicity against Anopheles mosquitoes. The granule formulations can be used as an effective biocontrol strategy against malaria-causing mosquitoes.

Anti-Zika Virus Activity and Isolation of Flavonoids from Ethanol Extracts of Curatella americana L. Leaves.

The ethnomedicinal plant Curatella americana L. (Dilleniaceae) is a common shrub in the Brazilian Cerrado, whose ethanolic extract showed significant in vitro anti-Zika virus activity by the MTT colorimetric method. Currently, there is no drug in clinical use specifically for the treatment of this virus; therefore, in this work, the antiviral and cytotoxic properties of the ethanolic extract, fractions, and compounds were evaluated. The ethanolic extract of the leaves showed no cytotoxicity for the human MRC-5 cell and was moderately cytotoxic for the Vero cell (CC50 161.5 ± 2.01 µg/mL). This extract inhibited the Zika virus multiplication cycle with an EC50 of 85.2 ± 1.65 µg/mL. This extract was fractionated using the liquid-liquid partition technique, and the ethyl acetate fraction showed significant activity against the Zika virus with an EC50 of 40.7 ± 2.33 µg/mL. From the ethyl acetate fraction, the flavonoids quercetin-3-O-hexosylgallate (1), quercetin-3-O-glucoside (2), and quercetin (5) were isolated, and in addition to these compounds, a mixture of quercetin-3-O-rhamnoside (3) and quercetin-3-O-arabinoside (4) was also obtained. The isolated compounds quercetin and quercetin-3-O-hexosylgallate inhibited the viral cytopathic effect at an EC50 of 18.6 ± 2.8 and 152.8 ± 2.0, respectively. Additionally, analyses by liquid chromatography coupled to a mass spectrometer allowed the identification of another 24 minor phenolic constituents present in the ethanolic extract and in the ethyl acetate fraction of this species.

Bioactive Molecules Derived from Plants in Managing Dengue Vector Aedes aegypti (Linn.).

Mosquitoes are the potential vectors of several viral diseases such as filariasis, malaria, dengue, yellow fever, Zika fever and encephalitis in humans as well as other species. Dengue, the most common mosquito-borne disease in humans caused by the dengue virus is transmitted by the vector Ae. aegypti. Fever, chills, nausea and neurological disorders are the frequent symptoms of Zika and dengue. Thanks to various anthropogenic activities such as deforestation, industrialized farming and poor drainage facilities there has been a significant rise in mosquitoes and vector-borne diseases. Control measures such as the destruction of mosquito breeding places, a reduction in global warming, as well as the use of natural and chemical repellents, mainly DEET, picaridin, temephos and IR-3535 have proven to be effective in many instances. Although potent, these chemicals cause swelling, rashes, and eye irritation in adults and children, and are also toxic to the skin and nervous system. Due to their shorter protection period and harmful nature towards non-target organisms, the use of chemical repellents is greatly reduced, and more research and development is taking place in the field of plant-derived repellents, which are found to be selective, biodegradable and harmless to non-target species. Many tribal and rural communities across the world have been using plant-based extracts since ancient times for various traditional and medical purposes, and to ward off mosquitoes and various other insects. In this regard, new species of plants are being identified through ethnobotanical surveys and tested for their repellency against Ae. aegypti. This review aims to provide insight into many such plant extracts, essential oils and their metabolites, which have been tested for their mosquitocidal activity against different life cycle forms of Ae. Aegypti, as well as for their efficacy in controlling mosquitoes.

Identification of desoxyrhapontigenin as a novel antiviral agent against congenital Zika virus infection.

Zika virus (ZIKV) infection arises as a global health threat owing to its association with Guillain-Barre syndrome and microcephaly in adults and fetuses since the most recent epidemics. Although extraordinary efforts have been underway globally to identify safe and effective treatments for ZIKV, therapeutic progressions seem to remain stagnant, especially for treating congenital ZIKV infection. Bio-compounds from medicinal plants evolutionarily optimized as drug-like molecules offer eligible sources of pharmaceuticals and lead drugs to fight against viral infections. Here, we identified desoxyrhapontigenin (DES), a naturally occurring bioactive product, as the strongest inhibitory compound against ZIKV infection among six conventional polyphenols in vitro. We also leveraged the trophoblast cell line, human trophoblast stem cells, and complex placental organoid models to provide solid evidence to support the anti-ZIKV bioactivity of DES. Notably, DES treatment effectively reduced the ZIKV burden in serum and target tissues, and correspondingly improved ZIKV-induced pathologic changes including weight loss, tissue inflammation, cell apoptosis, and adverse pregnancy outcomes, while it did not lead to obvious toxicity in both adult and pregnant mice. Furthermore, mechanistic studies revealed that DES could suppress ZIKV entry via dual mechanisms of direct targeting ZIKV E proteins and downregulating putative ZIKV receptors. These findings elucidate a previously unappreciated protective role of desoxyrhapontigenin against ZIKV infection both in vitro and in vivo, which shed light on the development of a novel and potent treatment for congenital ZIKV infection.

Bio-fabricated zinc oxide and cry protein nanocomposites: Synthesis, characterization, potentiality against Zika, malaria and West Nile virus vector's larvae and their impact on non-target organisms.

The role of mosquito vectors in spreading disastrous diseases to living organisms, especially to humans is inevitable and undeniable. The impacts of the available chemical and synthetic insecticides on non-specific organisms as well as on nature are being the reason behind the search for target-specific, biocompatible and eco-friendly alternatives. The Madhuca longifolia seed extract and cry proteins from Bacillus thuringiensis-based nanocomposites (Cp-Ml-ZnO NCs) were produced to conquer the above-mentioned issues. The Cp-Ml-ZnO NCs (100 µg/mL) expressed better scavenging potentiality on 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) radicals than Ml seed extract and Ml-ZnO NPs. The susceptibility of tested vector larvae to the Cp-Ml-ZnO NCs was Ae. aegypti ˃An. stephensi ˃ Cx. quinquefasciatus along with LC50-27.73, 34.81, and 42.54 µg/mL concentration. The target specificity and biocompatibility of Cp-Ml-ZnO NCs were authenticated by the results obtained by evaluating the efficacy on D. similis, A. salina, P. reticulata, G. affinis, and RBCs of goat blood. Thus the Cp-Ml-ZnO NCs could be adopted for the control of vector larvae.

A chalcone identified by in silico and in vitro assays possesses high larvicidal activity against Aedes aegypti.

The Aedes aegypti mosquito is a vector of important viral diseases in tropical countries, as Zika, Chikungunya and Dengue fever. The use of the chemical control of the insect life cycle is one of the most popular strategies used as prophylactic for the human population exposed. However, potential environmental and human toxicity, as well as the resistance phenomena acquired by the insects, are the main limitations for the available options. This scenario encourages the continuous search for more potent and less inconvenient chemical alternatives. In this paper, we report a potent in vitro larvicidal activity in Aedes aegypti found to a chalcone compound, previously mined by an exhaustive virtual screening by molecular docking calculations in an important protein for the larvae growth. The protein 3-hydroxykynurenine transaminase enzyme (PDB ID: 6MFB) was then combined with potential ligands provided by a homemade databank, containing secondary metabolites found in plants of the brazilian Caatinga biome. Structural rationalization of the compounds with high affinity pointed the chalcone class as most promising. Subsequent in vitro tests allowed the identification of a specific molecule with very high larvicidal potency (100% of lethality at 2.5 ppm). These results can be used in future and more refined studies, to propose a larvicidal formulation for direct application and the exploration of new compounds of this chemical class.

Anti-arboviral activity and chemical characterization of hispidulin and ethanolic extracts from Millingtonia hortensis L.f. and Oroxylum indicum (L.) Kurz (Bignoniaceae).

Millingtonia hortensis L.f. and Oroxylum indicum (L.) Kurz (Bignoniaceae) are native species from the Asian continent. They are popularly used in traditional medicine and their extracts are rich in flavonoids. In this work, ethanolic extracts of stems and leaves of these species were evaluated against the Chikungunya, Zika and Mayaro virus. The extracts were subjected to analysis by ultra-efficient liquid chromatography coupled to mass spectrometry. Additionally, M. hortensis leaves extract was fractionated, leading to the isolation of hispidulin. Anti-arboviral activity against the three viruses was detected for M. hortensis leaves extract with EC50 ranging from 37.8 to 134.1 µg/mL and for O. indicum stems extract with EC50 ranging from 18.6 to 55.9 µg/mL. Hispidulin inhibited viral cytopathic effect of MAYV (EC50 value 32.2 µM) and CHIKV (EC50 value 78.8 µM). In LC-DAD-ESI-MS/MS analysis we characterized 25 flavonoids confirming once again the presence of these substances in extracts of these species.