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Free-living amoebae include Acanthamoeba castellanii and Naegleria fowleri that are opportunistic protozoa responsible for life-threatening central nervous system infections with mortality rates over 90%. The rising number of cases and high mortality rates are indicative of the critical unmet need for the development of efficient drugs in order to avert future deaths. In this study, we assess the anti-amoebic capacity of a conducting polymer nanocomposite comprising polyaniline (PANI) and hexagonal boron nitride (hBN) against A. castellanii and N. fowleri . We observed significant amoebicidal and cysticidal effects using 100 μg/mL PANI/hBN ( P < 0.05). Further, the nanocomposite demonstrated negligible cytotoxicity toward HaCaT and primary human corneal epithelial cells (pHCECs). In evaluating the mode of inhibition of A. castellanii due to treatment with PANI/hBN, increased intracellular reactive oxygen species (ROS) was measured and scanning microscopy visualized the formation of pores in the amoebae. Overall, this study is suggestive of the potential of the PANI/hBN nanocomposite as a promising therapy for amoeba infections.

The combination of newly available genome sequence information on locusts together with high throughput genomics capabilities, novel approaches for genetic traceability, and their large size for easier handling makes locusts a valuable in vivo tool to study brain formation, functional adaptations, and neuropathogenesis during embryonic development in various environmental niches.

Several lines of evidence suggest the role of air-conditioning systems in the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Furthermore, the likelihood of novel coronavirus to take refuge inside a microbial Trojan horse, that is, Acanthamoeba , can further enhance possibility of SARS-CoV-2 transmission in the environment. Here we propose the use of various disinfection strategies that can be employed using filters with antimicrobial fabricated surfaces or using UV irradiation to achieve germicidal properties for removal of pathogenic microbes such as SARS-CoV-2 and amoebae in the ventilation systems.

Several lines of evidence suggest the presence of severe acute respiratory coronavirus-2 (SARS-CoV-2) in wastewater. The use of sewage water for irrigation is common in many developing countries, and it is only partially treated in the majority of countries with less than 10% of collected wastewater receiving any form of treatment globally. Wastewater is unsafe for human and animal consumption and contains impurities and microbial pathogens. Here, we pose the question of whether the reuse of untreated or partially treated wastewater for irrigation can expose susceptible populations and pets, leading to COVID-19 disease recurrence in the community? It is imperative to study the ecological relationships between humans, animals, and environmental health in relation to COVID-19 to contribute to a "One Health Concept" to design preventative strategies and attain optimal health for people, animals, and the environment.

Herein, we propose the use of novel adsorbents, namely micelle clay complexes comprising the clay montmorillonite, coupled with activated carbon for effective eradication of neuropathogenic microbes such as SARS-CoV-2 and Naegleria fowleri from water supplies for ablution/nasal irrigation. These can be incorporated easily to water collection devices, i.e., taps and water bottles, in the domestic setting. These filters are low cost, easy to install, and ideal disinfection systems. Such strategies are particularly useful for communities who have lack of access to safe water supplies, rely heavily on water storage tanks, or lack adequate water sanitation facilities, especially in developing countries.

The presence of SARS-CoV-2 in human wastewater together with poor quality of public drinking water supplies in developing countries is of concern. Additionally, the frequent use of contaminated water for bathing, nasal irrigation, swimming, and ablution can be a risk factor in contracting infectious agents such as the brain-eating amoebae and possibly SARS-CoV-2. The use of appropriate tap water filters should be encouraged to remove pathogenic microbes, together with restrained nasal irrigation (not forcing water inside nostrils vigorously) during ritual ablution or bathing to avoid dangerous consequences for populations residing in developing countries.

The current outbreak has led to renewed interest in developing novel disinfectants/drugs to kill "a species" for the benefit of "another species." While the discovery of new antimicrobials will ensure our ability to counter such threats in the short term, the development of drug resistance through natural selection will lead to the evolution of more "superbugs." In this regard, there is a need to understand viral perspective and associated molecular mechanisms and whether we can regulate viral strategies for our benefit to coexist in the long term.

Naegleria fowleri ( N. fowleri ) causes primary amoebic meningoencephalitis (PAM) which almost always results in death. N. fowleri is also known as "brain-eating amoeba" due to its literal infestation of the brain leading to an inflammatory response in the brain tissues. Currently, there is no single drug that is available to treat PAM, and most treatments are combinations of antifungal, anticancer, and anti-inflammatory drugs. Recently nanotechnology has gained attention in chemotherapeutic research converging on drug delivery, while oleic acid (OA) has shown positive effects on the human immune system and inflammatory processes. In continuation of our recent research in which we reported the effects of oleic acid conjugated with silver nanoparticles (OA-AgNPs) against free-living amoeba Acanthamoeba castellanii , in this report, we show their antiamoebic effects against N. fowleri . OA alone and its nanoconjugates were tested against the amoeba by using amoebicidal and host cell cytopathogenicity assays. Trypan blue exclusion assay was used to determine cell viability. The results revealed that OA-AgNPs exhibited significantly enhanced antiamoebic effects ( P < 0.05) against N. fowleri as compared to OA alone. Evidently, lactate dehydrogenase release shows reduced N. fowleri -mediated host cell cytotoxicity. Based on our study, we anticipate that further studies on OA-AgNPs could potentially provide an alternative treatment of PAM.

Naegleria fowleri and Balamuthia mandrillaris are protist pathogens that infect the central nervous system, causing primary amoebic meningoencephalitis and granulomatous amoebic encephalitis with mortality rates of over 95%. Quinazolinones and their derivatives possess a wide spectrum of biological properties, but their antiamoebic effects against brain-eating amoebae have never been tested before. In this study, we synthesized a variety of 34 novel arylquinazolinones derivatives (Q1-Q34) by altering both quinazolinone core and aryl substituents. To study the antiamoebic activity of these synthetic arylquinazolinones, amoebicidal and amoebistatic assays were performed against N. fowleri and B. mandrillaris . Moreover, amoebae-mediated host cells cytotopathogenicity and cytotoxicity assays were performed against human keratinocytes cells in vitro . The results revealed that selected arylquinazolinones derivatives decreased the viability of B. mandrillaris and N. fowleri significantly ( P < 0.05) and reduced cytopathogenicity of both parasites. Furthermore, these compounds were also found to be least cytotoxic against HaCat cells. Considering that nanoparticle-based materials possess potent in vitro activity against brain-eating amoebae, we conjugated quinazolinones derivatives with silver nanoparticles and showed that activities of the drugs were enhanced successfully after conjugation. The current study suggests that quinazolinones alone as well as conjugated with silver nanoparticles may serve as potent therapeutics against brain-eating amoebae.

Brain-eating amoebae including Acanthamoeba spp., Naegleria fowleri , and Balamuthia mandrillaris cause rare infections of the central nervous system that almost always result in death. The high mortality rate, lack of interest for drug development from pharmaceutical industries, and no available effective drugs present an alarming challenge. The current drugs employed in the management and therapy of these devastating diseases are amphotericin B, miltefosine, chlorhexidine, pentamidine, and voriconazole which are generally used in combination. However, clinical evidence shows that these drugs have limited efficacy and high host cell cytotoxicity. Repurposing of drugs is a practical approach to utilize commercially available, U.S. Food and Drug Administration approved drugs for one disease against rare diseases caused by brain-eating amoebae. In this Perspective, we highlight some of the success stories of drugs repositioned against neglected parasitic diseases and identify future potential for effective and sustainable drug development against brain-eating amoebae infections.

Acanthamoeba and macrophages exhibit significant parallels in biochemical, physiological, cellular, and functional aspects. Given the ability of Acanthamoeba to contribute to the evolutionary gain of pathogenicity of a variety of microbial pathogens, here we propose the use of Acanthamoeba as a paradigm to study SARS-CoV-2 pathogenicity, infectivity, and evasion of cellular immune defenses.

SARS-CoV-2 remains a significant burden on human health. Several lines of evidence suggest that surveillance of sewage and waste can provide an early warning sign for COVID-19 recurrence in a community. In support, SARS-CoV-2 traces were found in sewage in several countries. With this in mind, it is notable that pests, such as cockroaches, are exposed to pathogenic microbes routinely, yet thrive in polluted environments. Such species have likely developed mechanisms to protect themselves against pathogens. In support, recent studies showed that cockroaches possess potent antibacterial molecules to shield themselves from pathogenic bacteria. Among hundreds of molecules, some contained thiazine groups, imidazoles, chromene derivatives, isoquinoline group, sulfonamides, pyrrole-containing analogs, flavanones, and furanones. Here, we propose that cockroaches are a potential source of antiviral molecules to thwart infections. Because this is an unexploited resource for potential antivirals, we believe that cockroaches offer a unique source for novel bioactive molecule(s) to counter COVID-19 with huge clinical impact worldwide.

Although there is no reported genetic predisposition in contracting coronavirus disease 2019 (COVID-19), the mortality rate varies among different ethnic groups. Here we determined potential correlation between COVID-19 and spice consumption. The data from 163 countries including total cases, total deaths, and total recovered were analyzed. It was observed that there is a clear interrelated prevalence between the total number of COVID-19 cases per million population tested and the gram of spice supply per capita per day. Nations with lower consumptions of spices per capita showed greater number of COVID-19 cases per million population. This is not surprising as herbs and spices are well-known to boost immunity. Although the precise molecular mechanisms associated with spices and immunity are not completely understood, our findings led us to hypothesize that spice consumption plays a role in our ability to fight COVID-19; however, intensive research is needed to determine the translational value of these findings.

There is mounting evidence of the central nervous system manifestations associated with COVID-19, particularly in severe cases. Up to 25% of COVID-19 cases exhibit neurological manifestations associated with COVID-19. In view of the devastating nature of the disease due to severe acute respiratory syndrome coronavirus 2, here we debate intranasal drug delivery, in addition to intravenous delivery, as a therapeutic strategy in the management of COVID-19 cases with central nervous system involvement.

Brain-eating amoebae are known to harbor a plethora of viral, bacterial, protozoal, and fungal pathogens and safeguard these pathogens against disinfectants. Due to their ubiquitous distribution in the environment and their status as the trojan horse of the microbial world, amoebae can provide novel coronavirus a means to susceptible hosts and possible transmission to the central nervous system. Here, we hypothesize that pursuing the host that harbor "terror cells" is a valuable approach in eradicating novel coronavirus in affected communities.

Pathogenic free-living amoebae including Acanthamoeba spp., Balamuthia mandrillaris, and Naegleria fowleri cause infections of the central nervous system (CNS), which almost always prove fatal. The mortality rate is high with the CNS infections caused by these microbes despite modern developments in healthcare and antimicrobial chemotherapy. The low awareness, delayed diagnosis, and lack of effective drugs are major hurdles to overcome these challenges. Nanomaterials have emerged as vital tools for concurrent diagnosis and therapy, which are commonly referred to as theranostics. Nanomaterials offer highly sensitive diagnostic systems and viable therapeutic effects as a single modality. There has been good progress to develop nanomaterials based efficient theranostic systems against numerous kinds of tumors, but this field is yet immature in the context of infectious diseases, particularly parasitic infections. Herein, we describe the potential value of theranostic applications of nanomaterials against brain infections due to pathogenic amoebae.

Central nervous system (CNS) infections caused by free-living amoebae such as Acanthamoeba species and Naegleria fowleri are rare but fatal. A major challenge in the treatment against the infections caused by these amoebae is the discovery of novel compounds that can effectively cross the blood-brain barrier to penetrate the CNS. It is logical to test clinically approved drugs against CNS diseases for their potential antiamoebic effects since they are known for effective blood-brain barrier penetration and affect eukaryotic cell targets. The antiamoebic effects of clinically available drugs for seizures targeting gamma-amino butyric acid (GABA) receptor and ion channels were tested against Acanthamoeba castellanii belonging to the T4 genotype and N. fowleri. Three such drugs, namely, diazepam (Valium), phenobarbitone (Luminal), phenytoin (Dilantin), and their silver nanoparticles (AgNPs) were evaluated against both trophozoites and cysts stage. Drugs alone and drug conjugated silver nanoparticles were tested for amoebicidal, cysticidal, and host-cell cytotoxicity assays. Nanoparticles were synthesized by sodium borohydride reduction of silver nitrate with drugs as capping agents. Drug conjugated nanoconjugates were characterized by ultraviolet-visible (UV-vis) and Fourier transform infrared (FT-IR) spectroscopies and atomic force microscopy (AFM). In vitro moebicidal assay showed potent amoebicidal effects for diazepam, phenobarbitone, and phenytoin-conjugated AgNPs as compared to drugs alone against A. castellanii and N. fowleri. Furthermore, both drugs and drug conjugated AgNPs showed compelling cysticidal effects. Drugs conjugations with silver nanoparticles enhanced their antiacanthamoebic activity. Interestingly, amoeba-mediated host-cell cytotoxicity was also significantly reduced by drugs alone as well as their nanoconjugates. Since, these drugs are being used to target CNS diseases, their evaluation against brain-eating amoebae seems feasible due to advantages such as permeability of the blood-brain barrier, established pharmacokinetics and dynamics, and United States Food and Drug Administration (FDA) approval. Given the limited availability of effective drugs against brain-eating amoebae, the clinically available drugs tested here present potential for further in vivo studies.

The overall aim of this study was to determine whether conjugation with silver nanoparticles enhances effects of available drugs against primary amoebic meningoencephalitis due to Naegleria fowleri. Amphotericin B, Nystatin, and Fluconazole were conjugated with silver nanoparticles, and synthesis was confirmed using UV-visible spectrophotometry. Atomic force microscopy determined their size in range of 20-100 nm. To determine amoebicidal effects, N. fowleri were incubated with drugs-conjugated silver nanoparticles, silver nanoparticles alone, and drugs alone. The findings revealed that silver nanoparticles conjugation significantly enhanced antiamoebic effects of Nystatin and Amphotericin B but not Fluconazole at micromolar concentrations, compared with the drugs alone. For the first time, our findings showed that silver nanoparticle conjugation enhances efficacy of antiamoebic drugs against N. fowleri. Given the rarity of the disease and challenges in developing new drugs, it is hoped that modifying existing drugs to enhance their antiamoebic effects is a useful avenue that holds promise in improving the treatment of brain-eating amoebae infection due to N. fowleri.

Brain-eating amoebae (Acanthamoeba spp., Balamuthia mandrillaris, and Naegleria fowleri) can cause opportunistic infections involving the central nervous system. It is troubling that the mortality rate is more than 90% despite advances in antimicrobial chemotherapy over the last few decades. Here, we describe urgent key priorities for improving outcomes from infections due to brain-eating amoebae.

Brain infections due to Acanthamoeba spp., Balamuthia mandrillaris, and Naegleria fowleri often lead to death. Despite differences in the preferential sites of infection in the brain, the mode of delivery of drugs is often intravenous. Here, we discuss targeted therapeutic approach to affect parasite viability without affecting the host cells, with an eye to improve formulation of drugs and/or administration of drugs against brain-eating amoebae.