Papers by Patricio Rojas Silva
Supporting Information. Synthesis and evaluation of biological activities of bis(spiropyrazolone)... more Supporting Information. Synthesis and evaluation of biological activities of bis(spiropyrazolone)cyclopropanes: a potential application against leishmaniasis
The dissertation aim was to present natural products derived from four common edible medicinal pl... more The dissertation aim was to present natural products derived from four common edible medicinal plants that could be applied for solving leishmaniasis, obesity and type 2 diabetes. This research showed leishmanicidal natural compounds isolated from Cichorium intybus L. (Asteraceae), Cornus florida L. (Cornaceae), Eryngium foetidum L. (Apiaceae), which have been used traditionally as antiparasitic remedies. The roots of C. intybus (chicory) yielded four sesquiterpene lactones: (1) 11(S),13-dihydrolactucopicrin, (2) lactucopicrin, (3) 11(S),13-dihydrolactucin and (4) lactucin. Only compound 2 presented leishmanicidal activity (IC 50 24.8 μM). The bark of C. florida (flowering dogwood) afforded eight compounds: (1) betulinic acid, (2) ursolic acid, (3) β-sitosterol, (4) ergosta-4,6,8,22-tetraene-3-one, (5) 3β-O-acetyl betulinic acid, (6) 3-epideoxyflindissol, (7) 3β-O-cis-coumaroyl betulinic acid, (8) 3β-O-trans-coumaroyl betulinic acid. The most active leishmanicidal compounds were (4)...
Molecules, 2021
This work focuses on the search and development of drugs that may become new alternatives to the ... more This work focuses on the search and development of drugs that may become new alternatives to the commercial drugs currently available for treatment of leishmaniasis. We have designed and synthesized 12 derivatives of bis(spiropyrazolone)cyclopropanes. We then characterized their potential application in therapeutic use. For this, the in vitro biological activities against three eukaryotic models—S. cerevisiae, five cancer cell lines, and the parasite L. mexicana—were evaluated. In addition, cytotoxicity against non-cancerous mammalian cells has been evaluated and other properties of interest have been characterized, such as genotoxicity, antioxidant properties and, in silico predictive adsorption, distribution, metabolism, and excretion (ADME). The results that we present here represent a first screening, indicating two derivatives of bis(spiropyrazolone)cyclopropanes as good candidates for the treatment of leishmaniasis. They have good specificity against parasites with respect to ...
Journal of Agricultural and Food Chemistry, 2011
Two different strategies for investigating the likely fate, after ingestion, of natural, bioactiv... more Two different strategies for investigating the likely fate, after ingestion, of natural, bioactive berry constituents (anthocyanins and other non-nutritive flavonoids) are compared. A model of the human gastrointestinal tract (TIM-1) that mimicked the biological environment from the point of swallowing and ingestion through the duodenum, jejunum, and ileum (but not the colon) was used to monitor the stability and bioaccessibility of anthocyanins from both maqui berry and wild blueberry. TIM-1 revealed that most anthocyanins were bioaccessible between the second and third hours after intake. Alternatively, biolabeled anthocyanins and other flavonoids generated in vitro from berry and grape cell cultures were administered to in vivo (rodent) models, allowing measurement and tracking of the absorption and transport of berry constituents and clearance through the urinary tract and colon. The advantages and limitations of the alternative strategies are considered.
Nature, 2022
The SARS-CoV-2 Omicron BA.1 variant emerged in 20211 and has multiple mutations in its spike prot... more The SARS-CoV-2 Omicron BA.1 variant emerged in 20211 and has multiple mutations in its spike protein2. Here we show that the spike protein of Omicron has a higher affinity for ACE2 compared with Delta, and a marked change in its antigenicity increases Omicron’s evasion of therapeutic monoclonal and vaccine-elicited polyclonal neutralizing antibodies after two doses. mRNA vaccination as a third vaccine dose rescues and broadens neutralization. Importantly, the antiviral drugs remdesivir and molnupiravir retain efficacy against Omicron BA.1. Replication was similar for Omicron and Delta virus isolates in human nasal epithelial cultures. However, in lung cells and gut cells, Omicron demonstrated lower replication. Omicron spike protein was less efficiently cleaved compared with Delta. The differences in replication were mapped to the entry efficiency of the virus on the basis of spike-pseudotyped virus assays. The defect in entry of Omicron pseudotyped virus to specific cell types effe...
Comprehensive Reviews in Food Science and Food Safety, Apr 10, 2015
Quinoa (Chenopodium quinoa Willd., Amaranthaceae) is a grain-like, stress-tolerant food crop that... more Quinoa (Chenopodium quinoa Willd., Amaranthaceae) is a grain-like, stress-tolerant food crop that has provided subsistence, nutrition, and medicine for Andean indigenous cultures for thousands of years. Quinoa contains a high content of health-beneficial phytochemicals, including amino acids, fiber, polyunsaturated fatty acids, vitamins, minerals, saponins, phytosterols, phytoecdysteroids, phenolics, betalains, and glycine betaine. Over the past 2 decades, numerous food and nutraceutical products and processes have been developed from quinoa. Furthermore, 4 clinical studies have demonstrated that quinoa supplementation exerts significant, positive effects on metabolic, cardiovascular, and gastrointestinal health in humans. However, vast challenges and Direct inquiries to author Graf
New Microbes and New Infections
There are six different types of diarrheagenic Escherichia coli, each one with its own characteri... more There are six different types of diarrheagenic Escherichia coli, each one with its own characteristics. However, enterotoxigenic Escherichia coli (ETEC) is the main bacterial agent that causes diarrhea worldwide, and it is also associated with traveler’s diarrhea. ETEC strains could harbor one or two types of enterotoxins, so there are 3 varieties: ETEC-LT, ETEC-ST, and ETEC-LT/ST. The main goals of this study were: determine prevalence of enterotoxigenic E. coli (ETEC), enteroinvasiva E. coli (EIEC), Shigellae, and enteropathogenic E. coli (EPEC); determine the prevalence of the three varieties of ETEC; and finally make a genotyping analysis by pulse-field electrophoresis (PFGE) of ETEC isolates to show their genetic relation.
Virus Evolution, 2021
Characterisation of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genetic diversit... more Characterisation of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genetic diversity through space and time can reveal trends in virus importation and domestic circulation and permit the exploration of questions regarding the early transmission dynamics. Here, we present a detailed description of SARS-CoV-2 genomic epidemiology in Ecuador, one of the hardest hit countries during the early stages of the coronavirus-19 pandemic. We generated and analysed 160 whole genome sequences sampled from all provinces of Ecuador in 2020. Molecular clock and phylogeographic analysis of these sequences in the context of global SARS-CoV-2 diversity enable us to identify and characterise individual transmission lineages within Ecuador, explore their spatiotemporal distributions, and consider their introduction and domestic circulation. Our results reveal a pattern of multiple international importations across the country, with apparent differences between key provinces. Transmission li...
The dissertation aim was to present natural products derived from four common edible medicinal pl... more The dissertation aim was to present natural products derived from four common edible medicinal plants that could be applied for solving leishmaniasis, obesity and type 2 diabetes. This research showed leishmanicidal natural compounds isolated from Cichorium intybus L. (Asteraceae), Cornus florida L. (Cornaceae), Eryngium foetidum L. (Apiaceae), which have been used traditionally as antiparasitic remedies. The roots of C. intybus (chicory) yielded four sesquiterpene lactones: (1) 11(S),13-dihydrolactucopicrin, (2) lactucopicrin, (3) 11(S),13-dihydrolactucin and (4) lactucin. Only compound 2 presented leishmanicidal activity (IC 50 24.8 μM). The bark of C. florida (flowering dogwood) afforded eight compounds: (1) betulinic acid, (2) ursolic acid, (3) β-sitosterol, (4) ergosta-4,6,8,22-tetraene-3-one, (5) 3β-O-acetyl betulinic acid, (6) 3- epideoxyflindissol, (7) 3β-O-cis-coumaroyl betulinic acid, (8) 3β-O-trans-coumaroyl betulinic acid. The most active leishmanicidal compounds were (4...
SARS-CoV-2, the etiological agent of COVID-19, was first described in Wuhan, China in December 20... more SARS-CoV-2, the etiological agent of COVID-19, was first described in Wuhan, China in December 2019 and has now spread globally. Ecuador was the second country in South America to confirm cases and Guayaquil was one of the first cities in the world to experience high mortality due to COVID-19. The aim of this study was to describe the lineages circulating throughout the country and to compare the mutations in local variants, to the reference strain. In this work we used the MinION platform (Oxford Nanopore Technologies) to sequence the whole SARS-CoV-2 genomes of 119 patients from all provinces of Ecuador, using the ARTIC network protocols. Our data from lineage assignment of the one hundred and nineteen whole genomes revealed twenty different lineages. All genomes presented differences in the S gene compared to the Wuhan reference strain, being the D614G amino acid replacement the most common change. The B.1.1.119 lineage was the most frequent and was found in several locations in ...
IDCases
Background SARS-CoV-2 uses the human cell receptor angiotensin-converting enzyme (ACE2). ACE2 is ... more Background SARS-CoV-2 uses the human cell receptor angiotensin-converting enzyme (ACE2). ACE2 is widely present in the cardiovascular system including the myocardium and the conduction system. COVID-19 patients that present severe symptoms have been reported to have complications involving myocardial injuries caused by the virus. Here we report the detection of SARS-CoV-2 by whole genome sequencing in the endocardium of a patient with severe bradycardia. Case presentation We report a case of a 34-year-old male patient with COVID-19 tested by PCR, he started with gastrointestinal symptoms, however, he quickly deteriorated his hemodynamic state by means of myocarditis and bradycardia. After performing an endocardium biopsy, it was possible to identify the presence of SARS-CoV-2 in the heart tissue and to sequence its whole genome using the ARTIC-Network protocol and a modified tissue RNA extraction method. The patient’s outcome was improved after a permanent pacemaker was implanted. Conclusions It was possible to identify a SARS-CoV-2 clade 20A in the endocardium of the reported patient.
The Lancet Infectious Diseases
SSRN Electronic Journal
The permanence of rt-PCR positivity after a long time in COVID-19 patients has prompted the quest... more The permanence of rt-PCR positivity after a long time in COVID-19 patients has prompted the question of whether SARS-CoV-2 could cause a persistent infection or patients can become re-infected by this virus. Both possibilities could have critical implications for the management and control of COVID-19. Here we present the first confirmed case of SARS-CoV-2 reinfection in Ecuador and South America. Materials and methods: Our diagnostic laboratory detected a potential re-infection in one patient who was SARS-COv2 rt-PCR positive twice (in May and July 2020). The first laboratory-confirmed infection presented with mild symptoms and full recovery, reaffirmed by a negative RT-PCR test result obtained two weeks after symptom onset. More severe COVID-19-like symptoms presented again four weeks after the first event, and a third RT-PCR test was performed which resulted positive. The total RNA extraction (from the samples collected on both occasions) was sequenced in an Oxford Nanopore MinION using a tilling PCR protocol developed by the ARTIC-Network, and the reads were analyzed using the artic-medaka consensus generation tool. Anti SARS-CoV-2 IgM and IgG antibodies were investigated. Results: different SARS-CoV-2 variants were identified in each infection event. For the first infection, the genome was assigned to the B1.p9 GISAID clade while the variant associated with the second episode was assigned to the A.1.1 GISAID clade. High levels of both SARS-CoV-2 specific IgM and IgG were observed during the second event. Discussion: a patient with two COVID-19 events presented two different SARS-CoV-2 variants on each event, confirming reinfection. This phenomenon is still considered rare.
Microbiology Resource Announcements
We report the metagenome analysis of a bronchoalveolar lavage (BAL) fluid sample from a confirmed... more We report the metagenome analysis of a bronchoalveolar lavage (BAL) fluid sample from a confirmed coronavirus disease 2019 (COVID-19) case in Quito, Ecuador. Sequencing was performed using MinION technology.
Journal of medical entomology, Jan 12, 2018
1Instituto Nacional de Investigación en Salud Pública, Centro Nacional de Referencia e Investigac... more 1Instituto Nacional de Investigación en Salud Pública, Centro Nacional de Referencia e Investigación en Vectores, Quito, Ecuador, 2Universidad de Las Américas, Centro de Investigación Traslacional, Quito, Ecuador, 3Universidad Tecnologica Equinoccial, Centro de Investigación Biomédica, Facultad de Ciencias de la Salud Eugenio Espejo, Quito, Ecuador, 4Universidad San Francisco de Quito, Instituto de Microbiología, Quito, Ecuador, 5Universidad Central del Ecuador, Instituto de Biomedicina, Facultad de Biología, Quito, Ecuador, and 6Corresponding author, e-mail: [email protected]
Journal of Medical Entomology
The detection and identification of natural infections in sand flies by Leishmania protozoan spec... more The detection and identification of natural infections in sand flies by Leishmania protozoan species in endemic areas is a key factor in assessing the risk of leishmaniasis and in designing prevention and control measures for this infectious disease. In this study, we analyzed the Leishmania DNA using nuclear ribosomal internal transcript spacer (ITS) sequences. Parasite DNA was extracted from naturally infected, blood-fed sand flies collected in nine localities considered leishmaniasis-endemic foci in Ecuador. The species of parasites identified in sand flies were Leishmania major-like, Leishmania naiffi, Leishmania mexicana, Leishmania lainsoni, and "Leishmania sp. siamensis". Sand fly specimens of Brumptomyia leopoldoi, Mycropigomyia cayennensis, Nyssomyia yuilli yuilli, Nyssomyia trapidoi, Pressatia triacantha, Pressatia dysponeta, Psychodopygus carrerai carrerai, Psychodopygus panamensis, and Trichophoromyia ubiquitalis were found positive for Leishmania parasite. These findings contribute to a better understanding of the epidemiology and transmission dynamics of the disease in high-risk areas of Ecuador.
SARS-CoV-2, the etiological agent of COVID-19 was first described in Wuhan in December 2019 and h... more SARS-CoV-2, the etiological agent of COVID-19 was first described in Wuhan in December 2019 and has now spread globally. Ecuador was the second country in South America to report confirmed cases. The first case reported in Quito, the capital city of Ecuador, was a tourist who came from the Netherlands and presented symptoms on March 10th, 2020 (index case). In this work we used the MinION platform (Oxford Nanopore Technologies) to sequence the metagenome of the bronchoalveolar lavage (BAL) from this case reported, and subsequently we sequenced the whole genome of the index case and other three patients using the ARTIC network protocols. Our data from the metagenomic approach confirmed the presence of SARS-CoV-2 coexisting with pathogenic bacteria suggesting coinfection. Relevant bacteria found in the BAL metagenome were Streptococcus pneumoniae, Mycobacterium tuberculosis, Staphylococcus aureus and Chlamydia spp. Lineage assignment of the four whole genomes revealed three different ...
Quinoa (Chenopodium quinoa Willd., Amaranthaceae) is a grain-like, stress-tolerant food crop that... more Quinoa (Chenopodium quinoa Willd., Amaranthaceae) is a grain-like, stress-tolerant food crop that has provided subsistence, nutrition, and medicine for Andean indigenous cultures for thousands of years. Quinoa contains a high content of health-beneficial phytochemicals, including amino acids, fiber, polyunsaturated fatty acids, vitamins, minerals, saponins, phytosterols, phytoecdysteroids, phenolics, betalains, and glycine betaine. Over the past 2 decades, numerous food and nutraceutical products and processes have been developed from quinoa. Furthermore, 4 clinical studies have demonstrated that quinoa supplementation exerts significant, positive effects on metabolic, cardiovascular, and gastrointestinal health in humans. However, vast challenges and opportunities remain within the scientific, agricultural, and development sectors to optimize quinoa's role in the promotion of global human health and nutrition. Practical Application: This work can be used to identify specific research studies necessary to further understand the role that quinoa and its individual chemical constituents play in human health. The information presented also highlights open avenues for technological innovation and quinoa product improvement within the industrial sector.
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Papers by Patricio Rojas Silva