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in vitro

NOT Open Access | Characterization of mitochondrial carrier proteins of malaria parasite Plasmodium falciparum based on in vitro translation and reconstitution

June 26, 2020 - 15:34 -- NOT Open Access
Author(s): 
Nozawa A, Ito D, Ibrahim M, Santos HJ, Tsuboi T, Tozawa Y
Reference: 
Parasitol Int. 2020 Jun 20:102160

Members of the mitochondrial carrier (MC) family of membrane transporters play important roles in cellular metabolism. We previously established an in vitro reconstitution system for membrane transporters based on wheat germ cell-free translation system. We have now applied this reconstitution system to the comparative analysis of MC proteins from the malaria parasite Plasmodium falciparum and Saccharomyces cerevisiae. We synthesized twelve putative P. falciparum MCs and determined the transport activities of four of these proteins including PF3D7_1037300 protein (ADP/ATP translocator), PF3D7_1004800 protein (ADP/ATP translocator), PF3D7_1,202,200 protein (phosphate carrier), and PF3D7_1241600 protein (S-adenosylmethionine transporter).

NOT Open Access | Synthesis of Novel 1,2,3-Triazole Derivatives of Isocoumarins and 3,4-Dihydroisocoumarin with Potential Antiplasmodial Activity In Vitro

June 3, 2020 - 07:04 -- NOT Open Access
Author(s): 
da Silva Santos L, de Carvalho MFL, de Souza Pinto AC, da Fonseca AL, Dias Lopes JC, de Pilla Varotti F, de Freitas RP, Alves RB
Reference: 
Med Chem. 2020 Jun 2

Malaria greatly affects the world health, having caused more than 228 million cases only in 2018. The emergence of drug resistance is one of the main problems in its treatment, demonstrating the urge for the development of new antimalarial drugs.

NOT Open Access | In silico, in vitro and in vivo evaluation of natural Bignoniaceous naphthoquinones in comparison with atovaquone targeting the selection of potential antimalarial candidates

June 1, 2020 - 16:06 -- NOT Open Access
Author(s): 
do Nascimento MFA, Borgati TF, de Souza LCR, Tagliati CA, de Oliveira AB
Reference: 
Toxicol Appl Pharmacol. 2020 May 25:115074

The natural naphthoquinones lapachol, α- and β-lapachone are found in Bignoniaceous Brazilian plant species of the Tabebuia genus (synonym Handroanthus) and are recognized for diverse bioactivities, including as antimalarial. The aim of the present work was to perform in silico, in vitro and in vivo studies to evaluating the antimalarial potential of these three naphthoquinones in comparison with atovaquone, a synthetic antimalarial.

Antiviral Effects of Hydroxychloroquine and Type I Interferon on In Vitro Fatal Feline Coronavirus Infection

May 27, 2020 - 13:39 -- Open Access
Author(s): 
Takano T, Satoh K, Doki T, Tanabe T, Hohdatsu T
Reference: 
Viruses. 2020 May 24; 12(5):E576

Feline infectious peritonitis (FIP) is a viral disease with a high morbidity and mortality by the FIP virus (FIPV, virulent feline coronavirus). Several antiviral drugs for FIP have been identified, but many of these are expensive and not available in veterinary medicine. Hydroxychloroquine (HCQ) is a drug approved by several countries to treat malaria and immune-mediated diseases in humans, and its antiviral effects on other viral infections (e.g., SARS-CoV-2, dengue virus) have been confirmed.

Purification and production of Plasmodium falciparum zygotes from in vitro culture using magnetic column and Percoll density gradient

May 25, 2020 - 15:07 -- Open Access
Author(s): 
Yaxian Zhou, Alexis M. Grieser, Julie Do, Leslie S. Itsara, Ashley M. Vaughan and Anil K. Ghosh
Reference: 
Malaria Journal 2020 19:192, 25 May 2020

Plasmodium falciparum zygotes develop in the mosquito midgut after an infectious blood meal containing mature male and female gametocytes. Studies of mosquito-produced P. falciparum zygotes to elucidate their biology and development have been hampered by high levels of contaminating mosquito proteins and macromolecules present in zygote preparations. Thus, no zygote-specific surface markers have been identified to date. Here, a methodology is developed to obtain large quantities of highly purified zygotes using in vitro culture, including purification methods that include magnetic column cell separation (MACS) followed by Percoll density gradient centrifugation. This straightforward and effective approach provides ample material for studies to enhance understanding of zygote biology and identify novel zygote surface marker candidates that can be tested as transmission blocking vaccine (TBV) candidates.

Local emergence in Amazonia of Plasmodium falciparum k13 C580Y mutants associated with in vitro artemisinin resistance

May 13, 2020 - 14:50 -- Open Access
Author(s): 
Mathieu LC, Cox H, Musset L, et al.
Reference: 
Elife. 2020 May 12;9. pii: e51015

Antimalarial drug resistance has historically arisen through convergent de novo mutations in Plasmodium falciparum parasite populations in Southeast Asia and South America. For the past decade in Southeast Asia, artemisinins, the core component of first-line antimalarial therapies, have experienced delayed parasite clearance associated with several pfk13 mutations, primarily C580Y.

NOT Open Access | In silico evaluation and in vitro growth inhibition of Plasmodium falciparum by natural amides and synthetic analogs

May 12, 2020 - 17:53 -- NOT Open Access
Author(s): 
da Silva MA, Veloso MP, Kuehn CC, et al.
Reference: 
Parasitol Res. 2020 May 8

Malaria, caused by protozoa of the genus Plasmodium, is a disease that infects hundreds of millions of people annually, causing an enormous social burden in many developing countries. Since current antimalarial drugs are starting to face resistance by the parasite, the development of new therapeutic options has been prompted. The enzyme Plasmodium falciparum enoyl-ACP reductase (PfENR) has a determinant role in the fatty acid biosynthesis of this parasite and is absent in humans, making it an ideal target for new antimalarial drugs.

NOT Open Access | Vancomycin improves Plasmodium yoelii malaria parasite in vitro liver stage cultures by controlling Elizabethkingia anophelis, a bacterium in the microbiome of lab-reared Anopheles mosquitoes

May 6, 2020 - 15:01 -- NOT Open Access
Author(s): 
Shears MJ, Murphy SC
Reference: 
Mol Biochem Parasitol. 2020 Apr 30:111279

Studies of Plasmodium sporozoites and liver stages require dissection of Anopheles mosquitoes to obtain sporozoites for experiments. Sporozoites from the rodent parasite P. yoelii are routinely used to infect hepatocytes for liver stage culture, but sometimes these cultures become contaminated. Using standard microbiological techniques, a single colony type of Gram-negative rod-shaped bacteria was isolated from contaminated cultures.

NOT Open Access | In Vitro Screening of the Open-Source Medicines for Malaria Venture Malaria and Pathogen Boxes To Discover Novel Compounds with Activity against Balamuthia mandrillaris

April 29, 2020 - 14:34 -- NOT Open Access
Author(s): 
Christopher A. Rice, Luis Fernando Lares-Jiménez, Fernando Lares-Villa and Dennis E. Kyle
Reference: 
Antimicrob. Agents Chemother. April 2020 64:e02233-19

Balamuthia mandrillaris is an under-reported, pathogenic free-living amoeba that causes Balamuthia amoebic encephalitis (BAE) and cutaneous skin infections. Although cutaneous infections are not typically lethal, BAE with or without cutaneous involvement is usually fatal. This is due to the lack of drugs that are both efficacious and can cross the blood-brain barrier.

Effects of combined drug treatments on Plasmodium falciparum: In vitro assays with doxycycline, ivermectin and efflux pump inhibitors

April 27, 2020 - 12:53 -- Open Access
Author(s): 
Nodari R, Corbett Y, Varotto-Boccazzi I, Porretta D, Taramelli D, Epis S, Bandi C
Reference: 
PLoS ONE 15(4): e0232171

There is great concern regarding the rapid emergence and spread of drug-resistance in Plasmodium falciparum, the parasite responsible for the most severe form of human malaria. Parasite populations resistant to some or all the currently available antimalarial treatments are present in different world regions. Considering the need for novel and integrated approaches to control malaria, combinations of drugs were tested on P. falciparum. The primary focus was on doxycycline, an antibiotic that specifically targets the apicoplast of the parasite.

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