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1.
Adv Exp Med Biol ; 1340: 205-236, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34569027

RESUMO

Plasmodium falciparum, the parasitic agent that is responsible for a severe and dangerous form of human malaria, has a history of long years of cohabitation with human beings with attendant negative consequences. While there have been some gains in the fight against malaria through the application of various control measures and the use of chemotherapeutic agents, and despite the global decline in malaria cases and associated deaths, the continual search for new and effective therapeutic agents is key to achieving sustainable development goals. An important parasite survival strategy, which is also of serious concern to the scientific community, is the rate at which the parasites continually develop resistance to drugs. Among the key players in the parasite's ability to develop resistance, maintain cellular integrity, and survives within an unusual environment of the red blood cells are the molecular chaperones of the heat shock proteins (HSP) family. HSPs constitute a novel avenue for antimalarial drug discovery and by exploring their ubiquitous nature and multifunctional activities, they may be suitable targets for the discovery of multi-targets antimalarial drugs, needed to fight incessant drug resistance. In this chapter, features of selected families of plasmodial HSPs that can be exploited in drug discovery are presented. Also, known applications of HSPs in small molecule screening, their potential usefulness in high throughput drug screening, as well as possible challenges are highlighted.


Assuntos
Antimaláricos , Plasmodium , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Descoberta de Drogas , Proteínas de Choque Térmico/genética , Humanos , Plasmodium falciparum/genética
2.
Zhongguo Zhong Yao Za Zhi ; 46(18): 4849-4864, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34581097

RESUMO

As a unicellular organism, Plasmodium displays a panoply of lipid metabolism pathways that are seldom found together in a unicellular organism. These pathways mostly involve the Plasmodium-encoded enzymatic machinery and meet the requirements of membrane synthesis during the rapid cell growth and division throughout the life cycle. Different lipids have varied synthesis and meta-bolism pathways. For example, the major phospholipids are synthesized via CDP-diacylglycerol-dependent pathway in prokaryotes and de novo pathway in eukaryotes, and fatty acids are synthesized mainly via type Ⅱ fatty acid synthesis pathway. The available studies have demonstrated the impacts of artemisinin and its derivatives, the front-line compounds against malaria, on the lipid metabolism of Plasmodium. Therefore, this article reviewed the known lipid metabolism pathways and the effects of artemisinin and its derivatives on these pathways, aiming to deepen the understanding of lipid synthesis and metabolism in Plasmodium and provide a theoretical basis for the research on the mechanisms and drug resistance of artemisinin and other anti-malarial drugs.


Assuntos
Antimaláricos , Artemisininas , Malária , Plasmodium , Antimaláricos/farmacologia , Artemisininas/farmacologia , Artemisininas/uso terapêutico , Humanos , Metabolismo dos Lipídeos , Malária/tratamento farmacológico
3.
Biol Lett ; 17(9): 20210271, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34493062

RESUMO

Parasite range expansions are a direct consequence of globalization and are an increasing threat to biodiversity. Here, we report a recent range expansion of the SGS1 strain of a highly invasive parasite, Plasmodium relictum, to two non-migratory passerines in North America. Plasmodium relictum is considered one of the world's most invasive parasites and causes the disease avian malaria: this is the first reported case of SGS1 in wild non-migratory birds on the continent. Using a long-term database where researchers report avian malaria parasite infections, we summarized our current understanding of the geographical range of SGS1 and its known hosts. We also identified the most likely geographical region of this introduction event using the MSP1 allele. We hypothesize that this introduction resulted from movements of captive birds and subsequent spillover to native bird populations, via the presence of competent vectors and ecological fitting. Further work should be conducted to determine the extent to which SGS1 has spread following its introduction in North America.


Assuntos
Malária Aviária , Parasitos , Plasmodium , Animais , Animais Selvagens , Malária Aviária/epidemiologia , América do Norte/epidemiologia
4.
Emerg Infect Dis ; 27(10): 2700-2703, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34545786

RESUMO

We detected 2 natural, asymptomatic Plasmodium inui monoinfections in humans in Malaysia by using nested PCR on concentrated high-volume blood samples. We found a P. inui-positive Anopheles cracens mosquito in the same site as the human infections. Investigators should use ultrasensitive detection methods to identify simian malaria parasite transmission in humans.


Assuntos
Anopheles , Malária , Plasmodium , Animais , Humanos , Malária/epidemiologia , Malásia/epidemiologia , Mosquitos Vetores , Plasmodium/genética
5.
Anal Chem ; 93(37): 12793-12800, 2021 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-34496566

RESUMO

The World Health Organization (WHO) estimates that over three billion people are at risk of acquiring malaria, a parasitic infection that produces more than 200 million new infections and nearly half a million deaths each year. Expanding the access to early diagnosis and treatment is one of the most effective ways to prevent disease complications, reduce patient mortality, and curb the community transmission. However, none of the diagnostic methods used currently for malaria detection, including light microscopy, polymerase chain reaction (PCR), and rapid diagnostic tests (RDTs), can provide simultaneously fast results, high sensitivity, and parasitaemia quantitation with minimal user intervention. Here, we present a magneto-immunoassay that, based on the unique combination of magnetic beads (MB), an enzymatic signal amplifier (Poly-HRP), and chemiluminescence detection, provides fast, sensitive, and quantitative malaria diagnosis with easy user manipulation. This assay quantifies Plasmodium falciparum lactate dehydrogenase (PfLDH) in lysed whole blood samples in <15 min, exhibiting a limit of detection (LOD) of 0.02 ng mL-1 and providing patient stratification consistent with the reference methods. These figures of merit surpass the performance of the magneto-immunoassays reported previously for Plasmodium detection and demonstrate for the first time that the proposed combination of MB, Poly-HRP, and chemiluminescence detection produces extremely fast, simple, and efficient assays that approach the requirements of point-of-care (POC) malaria surveillance.


Assuntos
Malária , Plasmodium , Humanos , Imunoensaio , Malária/diagnóstico , Plasmodium falciparum , Sensibilidade e Especificidade
6.
Anal Chem ; 93(36): 12175-12180, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34469115

RESUMO

Malaria and typhoid fever are two febrile illnesses prevalent in the tropics that often present overlapping symptoms. In this work, we demonstrate an optical reader-based diagnostics platform for rapid codetection and quantification of two antigen targets: lipopolysaccharide (LPS) for typhoid fever and plasmodium lactate dehydrogenase (pLDH) for malaria infections. We report a limit of detection (LoD) of 5 ng/mL for LPS and 10 ng/mL for pLDH in a spiked serum test. We also validated the duplex test's performance of differentiating malaria infection, typhoid fever infection, and coinfection by testing clinical samples in human serum. Our platform provides the potential for further multiplexing by encoding different color codes to various detection targets. The rapid result (∼15 min), low cost (∼$2), and minimal volume requirement for human serum clinical samples (4 µL) of our diagnostic platform offer great potential for deployment in resource-limited settings to help distinguish common causes for acute febrile illnesses at the point-of-need.


Assuntos
Malária , Plasmodium , Febre Tifoide , Humanos , L-Lactato Desidrogenase , Malária/diagnóstico , Sistemas Automatizados de Assistência Junto ao Leito , Sensibilidade e Especificidade , Febre Tifoide/diagnóstico
7.
Braz J Biol ; 83: e247219, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34468526

RESUMO

Military conflicts have been significant obstacles in detecting and treating infectious disease diseases due to the diminished public health infrastructure, resulting in malaria endemicity. A variety of violent and destructive incidents were experienced by FATA (Federally Administered Tribal Areas). It was a struggle to pursue an epidemiological analysis due to continuing conflict and Talibanization. Clinical isolates were collected from Bajaur, Mohmand, Khyber, Orakzai agencies from May 2017 to May 2018. For Giemsa staining, full blood EDTA blood samples have been collected from symptomatic participants. Malaria-positive microscopy isolates were spotted on filter papers for future Plasmodial molecular detection by nested polymerase chain reaction (nPCR) of small subunit ribosomal ribonucleic acid (ssrRNA) genes specific primers. Since reconfirming the nPCR, a malariometric study of 762 patients found 679 positive malaria cases. Plasmodium vivax was 523 (77%), Plasmodium falciparum 121 (18%), 35 (5%) were with mixed-species infection (P. vivax plus P. falciparum), and 83 were declared negative by PCR. Among the five agencies of FATA, Khyber agency has the highest malaria incidence (19%) with followed by P. vivax (19%) and P. falciparum (4.1%). In contrast, Kurram has about (14%), including (10.8%) P. vivax and (2.7%) P. falciparum cases, the lowest malaria epidemiology. Surprisingly, no significant differences in the distribution of mixed-species infection among all five agencies. P. falciparum and P. vivax were two prevalent FATA malaria species in Pakistan's war-torn area. To overcome this rising incidence of malaria, this study recommends that initiating malaria awareness campaigns in school should be supported by public health agencies and malaria-related education locally, targeting children and parents alike.


Assuntos
Plasmodium , Criança , Humanos , Epidemiologia Molecular , Paquistão/epidemiologia , Plasmodium/genética , Plasmodium falciparum/genética , Plasmodium vivax/genética
8.
Elife ; 102021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34372970

RESUMO

Background: National Malaria Control Programmes (NMCPs) currently make limited use of parasite genetic data. We have developed GenRe-Mekong, a platform for genetic surveillance of malaria in the Greater Mekong Subregion (GMS) that enables NMCPs to implement large-scale surveillance projects by integrating simple sample collection procedures in routine public health procedures. Methods: Samples from symptomatic patients are processed by SpotMalaria, a high-throughput system that produces a comprehensive set of genotypes comprising several drug resistance markers, species markers and a genomic barcode. GenRe-Mekong delivers Genetic Report Cards, a compendium of genotypes and phenotype predictions used to map prevalence of resistance to multiple drugs. Results: GenRe-Mekong has worked with NMCPs and research projects in eight countries, processing 9623 samples from clinical cases. Monitoring resistance markers has been valuable for tracking the rapid spread of parasites resistant to the dihydroartemisinin-piperaquine combination therapy. In Vietnam and Laos, GenRe-Mekong data have provided novel knowledge about the spread of these resistant strains into previously unaffected provinces, informing decision-making by NMCPs. Conclusions: GenRe-Mekong provides detailed knowledge about drug resistance at a local level, and facilitates data sharing at a regional level, enabling cross-border resistance monitoring and providing the public health community with valuable insights. The project provides a rich open data resource to benefit the entire malaria community. Funding: The GenRe-Mekong project is funded by the Bill and Melinda Gates Foundation (OPP11188166, OPP1204268). Genotyping and sequencing were funded by the Wellcome Trust (098051, 206194, 203141, 090770, 204911, 106698/B/14/Z) and Medical Research Council (G0600718). A proportion of samples were collected with the support of the UK Department for International Development (201900, M006212), and Intramural Research Program of the National Institute of Allergy and Infectious Diseases.


Assuntos
Controle de Doenças Transmissíveis/estatística & dados numéricos , Erradicação de Doenças/estatística & dados numéricos , Resistência a Medicamentos/genética , Malária/prevenção & controle , Plasmodium/genética , Animais , Ásia Sudeste , Bangladesh , República Democrática do Congo , Índia , Plasmodium/efeitos dos fármacos
9.
Trends Parasitol ; 37(9): 777-779, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34332896

RESUMO

Plasmodium merozoites invade erythrocytes in a stepwise manner through ligand binding, calcium signaling, and membrane deformation. Using a recently developed light-sheet microscope, Geoghegan et al. investigated invasion with unprecedented temporal resolution. Their spectacular footage revealed roles for host cell cholesterol and pore formation at the parasite-host cell interface.


Assuntos
Malária , Plasmodium , Animais , Merozoítos , Microscopia , Proteínas de Protozoários
12.
Artigo em Inglês | MEDLINE | ID: mdl-34407161

RESUMO

The majority of malaria cases in South America occur in rural areas of the Amazon region. Although these areas have a significant impact on malaria cases, few entomological studies have been carried out there. This study aimed to describe entomological parameters in settlements in Rondonia State, Brazil. Collections of anopheles were carried out using the Protected Human Attraction Technique (PHAT). The risk and the potential for malaria transmission were assessed using the human biting rate (HBR), the sporozoite rate (SR) and the entomological inoculation rate (EIR). The results confirmed that Nyssorhynchus darlingi is the predominant species in the two studied locations. Although settlement in the two study sites has occurred at different times, the species richness found was low, showing that environmental changes caused by anthropological actions have probably favor the adaptation of Ny. darlingi species. From the total of 615 anopheline mosquitoes assessed, seven (1.1%) were positive for Plasmodium sp. infections. The EIR revealed that Ny. darlingi contributes to malaria transmission in both locations, as it was responsible for 0.05 infectious bites in humans at night in the old settlement and 0.02 in the recent occupation. In the two study sites, the biting occurred more frequently at dusk. Nyssorhynchus darlingi was prevalent in areas of recent colonization but, even when present in a low density, this species could maintain the transmission of malaria in the older settlement. The entomological information obtained in this study is important and may aid the selection of vector control actions in these locations.


Assuntos
Anopheles , Malária , Plasmodium , Animais , Brasil , Humanos , Mosquitos Vetores
13.
Front Cell Infect Microbiol ; 11: 685239, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34414129

RESUMO

Malaria caused by Plasmodium species and transmitted by Anopheles mosquitoes affects large human populations, while Ixodes ticks transmit Babesia species and cause babesiosis. Babesiosis in animals has been known as an economic drain, and human disease has also emerged as a serious healthcare problem in the last 20-30 years. There is limited literature available regarding pathogenesis, immunity, and disease caused by Babesia spp. with their genomes sequenced only in the last decade. Therefore, using previous studies on Plasmodium as the foundation, we have compared similarities and differences in the pathogenesis of Babesia and host immune responses. Sexual life cycles of these two hemoparasites in their respective vectors are quite similar. An adult Anopheles female can take blood meal several times in its life such that it can both acquire and transmit Plasmodia to hosts. Since each tick stage takes blood meal only once, transstadial horizontal transmission from larva to nymph or nymph to adult is essential for the release of Babesia into the host. The initiation of the asexual cycle of these parasites is different because Plasmodium sporozoites need to infect hepatocytes before egressed merozoites can infect erythrocytes, while Babesia sporozoites are known to enter the erythrocytic cycle directly. Plasmodium metabolism, as determined by its two- to threefold larger genome than different Babesia, is more complex. Plasmodium replication occurs in parasitophorous vacuole (PV) within the host cells, and a relatively large number of merozoites are released from each infected RBC after schizogony. The Babesia erythrocytic cycle lacks both PV and schizogony. Cytoadherence that allows the sequestration of Plasmodia, primarily P. falciparum in different organs facilitated by prominent adhesins, has not been documented for Babesia yet. Inflammatory immune responses contribute to the severity of malaria and babesiosis. Antibodies appear to play only a minor role in the resolution of these diseases; however, cellular and innate immunity are critical for the clearance of both pathogens. Inflammatory immune responses affect the severity of both diseases. Macrophages facilitate the resolution of both infections and also offer cross-protection against related protozoa. Although the immunosuppression of adaptive immune responses by these parasites does not seem to affect their own clearance, it significantly exacerbates diseases caused by coinfecting bacteria during coinfections.


Assuntos
Anopheles , Babesia , Ixodes , Parasitos , Plasmodium , Animais , Eritrócitos , Feminino , Humanos , Mosquitos Vetores
14.
Front Cell Infect Microbiol ; 11: 654216, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34262880

RESUMO

Malaria transmission relies on parasite-mosquito midgut interaction. The interactive proteins are hypothesized to be ideal targets to block malaria transmission to mosquitoes. We chose 76 genes that contain signal peptide-coding regions and are upregulated and highly abundant at sexual stages. Forty-six of these candidate genes (60%) were cloned and expressed using the baculovirus expression system in insect cells. Six of them, e.g., PF3D7_0303900, PF3D7_0406200 (Pfs16), PF3D7_1204400 (Pfs37), PF3D7_1214800, PF3D7_1239400, and PF3D7_1472800 were discovered to interact with blood-fed mosquito midgut lysate. Previous works showed that among these interactive proteins, knockout the orthologs of Pfs37 or Pfs16 in P. berghei reduced oocysts in mosquitoes. Here we further found that anti-Pfs16 polyclonal antibody significantly inhibited P. falciparum transmission to Anopheles gambiae. Investigating these candidate proteins will improve our understanding of malaria transmission and discover new targets to break malaria transmission.


Assuntos
Malária , Parasitos , Plasmodium , Animais , Mosquitos Vetores , Plasmodium falciparum/genética
15.
Immunobiology ; 226(5): 152091, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34303920

RESUMO

The spike protein of coronavirus is key target for drug development and other pharmacological interventions. In current study, we performed an integrative approach to predict antigenic sites in SARS-CoV-2 spike receptor binding domain and found nine potential antigenic sites. The predicted antigenic sites were then assessed for possible molecular similarity with other known antigens in different organisms. Out of nine sites, seven sites showed molecular similarity with 54 antigenic determinants found in twelve pathogenic bacterial species (Mycobacterium tuberculosis, Mycobacterium leprae, Bacillus anthracis, Borrelia burgdorferi, Clostridium perfringens, Clostridium tetani, Helicobacter Pylori, Listeria monocytogenes, Staphylococcus aureus, Streptococcus pyogenes, Vibrio cholera and Yersinia pestis), two malarial parasites (Plasmodium falciparum and Plasmodium knowlesi) and influenza virus A. Most of the bacterial antigens that displayed molecular similarity with antigenic sites in SARS-CoV-2 RBD (receptor binding domain) were toxins and virulent factors. Antigens from Mycobacterium that showed similarity were mainly involved in modulating host cell immune response and ensuring persistence and survival of pathogen in host cells. Presence of a large number of antigenic determinants, similar to those in highly pathogenic microorganisms, not merely accounts for complex etiology of the disease but also provides an explanation for observed pathophysiological complications, such as deregulated immune response, unleashed or dysregulated cytokine secretion (cytokine storm), multiple organ failure etc., that are more evident in aged and immune-compromised patients. Over-representation of antigenic determinants from Plasmodium and Mycobacterium in all antigenic sites suggests that anti-malarial and anti-TB drugs can prove to be clinical beneficial for COVID-19 treatment. Besides this, anti-leprosy, anti-lyme, anti-plague, anti-anthrax drugs/vaccine etc. are also expected to be beneficial in COVID-19 treatment. Moreover, individuals previously immunized/vaccinated or had previous history of malaria, tuberculosis or other disease caused by fifteen microorganisms are expected to display a considerable degree of resistance against SARS-CoV-2 infection. Out of the seven antigenic sites predicted in SARS-CoV-2, a part of two antigenic sites were also predicted as potent T-cell epitopes (KVGGNYNYL444-452 and SVLYNSASF366-374) against MHC class I and three (KRISNCVADYSVLYN356-370, DLCFTNVYADSFVI389-402, and YRVVVLSFELLHA508-520) against MHC class II. All epitopes possessed significantly lower predicted IC50 value which is a prerequisite for a preferred vaccine candidate for COVID-19.


Assuntos
Antígenos Virais/imunologia , Epitopos de Linfócito T/imunologia , Peptídeos/imunologia , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Bactérias/imunologia , Sítios de Ligação , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Vírus da Influenza A/imunologia , Plasmodium/imunologia , Domínios Proteicos
16.
Trends Parasitol ; 37(9): 775-776, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34275728

RESUMO

Anopheles mosquitoes feed on plant nectars as their main source of sugar. Wang et al. show that Asaia bacteria proliferate in the midgut of mosquitoes that feed on glucose or trehalose. Asaia increases the lumenal pH by downregulating mosquito vacuolar ATPase expression, therefore increasing Plasmodium gametogenesis and vector competence.


Assuntos
Anopheles , Malária , Plasmodium , Animais , Mosquitos Vetores , Açúcares
17.
Front Cell Infect Microbiol ; 11: 687019, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34195101

RESUMO

Plasmodium is a genus of apicomplexan parasites which replicate in the liver before causing malaria. Plasmodium vivax can also persist in the liver as dormant hypnozoites and cause clinical relapse upon activation, but the molecular mechanisms leading to activation have yet to be discovered. In this study, we use high-resolution microscopy to characterize temporal changes of the P. vivax liver stage tubovesicular network (TVN), a parasitophorous vacuole membrane (PVM)-derived network within the host cytosol. We observe extended membrane clusters, tubules, and TVN-derived vesicles present throughout P. vivax liver stage development. Additionally, we demonstrate an unexpected presence of the TVN in hypnozoites and observe some association of this network to host nuclei. We also reveal that the host water and solute channel aquaporin-3 (AQP3) associates with TVN-derived vesicles and extended membrane clusters. AQP3 has been previously shown to localize to the PVM of P. vivax hypnozoites and liver schizonts but has not yet been shown in association to the TVN. Our results highlight host-parasite interactions occur in both dormant and replicating liver stage P. vivax forms and implicate AQP3 function during this time. Together, these findings enhance our understanding of P. vivax liver stage biology through characterization of the TVN with an emphasis on the presence of this network in dormant hypnozoites.


Assuntos
Malária Vivax , Plasmodium , Animais , Fígado , Plasmodium vivax , Esquizontes
18.
Front Cell Infect Microbiol ; 11: 688380, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34327152

RESUMO

Malaria is still today one of the most concerning diseases, with 219 million infections in 2019, most of them in Sub-Saharan Africa and Latin America, causing approx. 409,000 deaths per year. Despite the tremendous advances in malaria treatment and prevention, there is still no vaccine for this disease yet available and the increasing parasite resistance to already existing drugs is becoming an alarming issue globally. In this context, several potential targets for the development of new drug candidates have been proposed and, among those, the de novo biosynthesis pathway for the B6 vitamin was identified to be a promising candidate. The reason behind its significance is the absence of the pathway in humans and its essential presence in the metabolism of major pathogenic organisms. The pathway consists of two enzymes i.e. Pdx1 (PLP synthase domain) and Pdx2 (glutaminase domain), the last constituting a transient and dynamic complex with Pdx1 as the prime player and harboring the catalytic center. In this review, we discuss the structural biology of Pdx1 and Pdx2, together with and the understanding of the PLP biosynthesis provided by the crystallographic data. We also highlight the existing evidence of the effect of PLP synthesis inhibition on parasite proliferation. The existing data provide a flourishing environment for the structure-based design and optimization of new substrate analogs that could serve as inhibitors or even suicide inhibitors.


Assuntos
Malária , Plasmodium , Glutaminase , Humanos , Plasmodium falciparum , Vitamina B 6
19.
Genetica ; 149(4): 217-237, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34254217

RESUMO

The biological meaning of low complexity regions in the proteins of Plasmodium species is a topic of discussion in evolutionary biology. There is a debate between selectionists and neutralists, who either attribute or do not attribute an effect of low-complexity regions on the fitness of these parasites, respectively. In this work, we comparatively study 22 Plasmodium species to understand whether their low complexity regions undergo a neutral or, rather, a selective and species-dependent evolution. The focus is on the connection between the codon repertoire of the genetic coding sequences and the occurrence of low complexity regions in the corresponding proteins. The first part of the work concerns the correlation between the length of plasmodial proteins and their propensity at embedding low complexity regions. Relative synonymous codon usage, entropy, and other indicators reveal that the incidence of low complexity regions and their codon bias is species-specific and subject to selective evolutionary pressure. We also observed that protein length, a relaxed selective pressure, and a broad repertoire of codons in proteins, are strongly correlated with the occurrence of low complexity regions. Overall, it seems plausible that the codon bias of low-complexity regions contributes to functional innovation and codon bias enhancement of proteins on which Plasmodium species rest as successful evolutionary parasites.


Assuntos
Uso do Códon , Evolução Molecular , Plasmodium/genética , Proteínas de Protozoários/química , Proteínas de Protozoários/genética , Sequências Repetitivas de Aminoácidos , Seleção Genética
20.
BMC Res Notes ; 14(1): 264, 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34238361

RESUMO

OBJECTIVE: Malaria is a major global health concern with the urgent need for new treatment alternatives due to the alarming increase of drug-resistant Plasmodium strains. Chalcones and its derivatives are important pharmacophores showing antimalarial activity. Determination of the pharmacokinetic variables at the preliminary step of drug development for any drug candidates is an essential component of in vivo antimalarial efficacy tests. Substandard pharmacokinetic variables are often responsible for insufficient therapeutic effect. Therefore, three chalcone derivatives, 1, 2, and 3, having antimalarial potency were studied further for potential therapeutic efficacy. RESULTS: In vivo pharmacokinetic studies of these three derivatives were performed on New Zealand White rabbits. The three derivatives were administered intra-peritoneally or orally at effective dose concentration and blood samples at different time points were collected. The determination of drug concentration was done through reverse phase-high performance liquid chromatography. The peak plasma concentration of derivative 1, 2, and 3 were 1.96 ± 0.46 µg/mL (intraperitoneal route), 69.89 ± 5.49 µg/mL (oral route), and 3.74 ± 1.64 µg/mL (oral route). The results indicate a very low bioavailability of these derivatives. The present study gives a benchmark to advance the investigation of more derivatives in order to revamp the pharmacokinetic variables while maintaining both potency and metabolic constancy.


Assuntos
Antimaláricos , Chalcona , Chalconas , Malária , Plasmodium , Animais , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Chalcona/farmacologia , Chalcona/uso terapêutico , Chalconas/uso terapêutico , Malária/tratamento farmacológico , Plasmodium falciparum , Coelhos
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