Javier Sánchez Céspedes - Academia.edu (original) (raw)

Papers by Javier Sánchez Céspedes

Journal of Medical Virology

The objectives of this work were to assess the diagnostic sensitivity and specificity of nasophar... more The objectives of this work were to assess the diagnostic sensitivity and specificity of nasopharyngeal (NP) swabs for viral community‐acquired pneumonia (CAP) and the performance of pneumonia severity index (PSI) and CURB‐65 severity scores in the viral CAP in adults. A prospective observational cohort study of consecutive 341 hospitalized adults with CAP was performed between January 2018 and March 2020. Demographics, comorbidities, symptoms/signs, analytical data, severity scores, antimicrobials, and outcomes were recorded. Blood, NP swabs, sputum, and urine samples were collected at admission and assayed by multiplex real time‐PCR, bacterial cultures, and Streptococcus pneumoniae and Legionella pneumophila antigens detection, to determine the etiologies and quantify the viral load. The etiology was identified in 174 (51.0%) patients, and in 85 (24.9%) it was viral, the most frequent rhinovirus and influenza virus. The sensitivity of viral detection in sputum (50.7%) was higher t...

Scientific Reports

The main objective was to evaluate the viability of the SARS-CoV-2 viral particles excreted in st... more The main objective was to evaluate the viability of the SARS-CoV-2 viral particles excreted in stools. In addition, we aimed to identify clinical factors associated with the detection of SARS-CoV-2 RNA in feces, and to determine if its presence is associated with an unfavorable clinical outcome, defined as intensive care unit (ICU) admission and/or death. A prospective multicenter cohort study of COVID-19 adult patients, with confirmed SARS-CoV-2 infection by RT-PCR assay in nasopharyngeal (NP) swabs admitted to four hospitals in Spain, from March 2020 to February 2021. Sixty-two adult COVID-19 patients had stool samples collected at admission and/or during the follow up, with a total of 79 stool samples. SARS-CoV-2 RNA was detected in stool samples from 27 (43.5%) out of the 62 patients. Replicative virus, measured by the generation of cytopathic effect in cell culture and subsequent RT-PCR confirmation of a decrease in the Ct values, was not found in any of these stool samples. Fe...

This article cites 13 articles, 10 of which can be accessed free

International Journal of Molecular Sciences, 2021

Human adenoviruses (HAdVs) display a wide range of tissue tropism and can cause an array of sympt... more Human adenoviruses (HAdVs) display a wide range of tissue tropism and can cause an array of symptoms from mild respiratory illnesses to disseminated and life-threatening infections in immunocompromised individuals. However, no antiviral drug has been approved specifically for the treatment of HAdV infections. Herein, we report our continued efforts to optimize salicylamide derivatives and discover compound 16 (JMX0493) as a potent inhibitor of HAdV infection. Compound 16 displays submicromolar IC50 values, a higher selectivity index (SI > 100) and 2.5-fold virus yield reduction compared to our hit compound niclosamide. Moreover, unlike niclosamide, our mechanistic studies suggest that the antiviral activity of compound 16 against HAdV is achieved through the inhibition of viral particle escape from the endosome, which bars subsequent uncoating and the presentation of lytic protein VI.

International Journal of Antimicrobial Agents, 2007

S277 (ceftazidime, ceftriaxone, cefpodoxime, and aztreonam) according to Clinical and Laboratory ... more S277 (ceftazidime, ceftriaxone, cefpodoxime, and aztreonam) according to Clinical and Laboratory Standards Institute (CLSI) guidelines. As phenotypic confirmatory test, three different ESBL Etest strips (AB Biodisk, Sweden) were used, i.e., ceftazidime, cefotaxime, and cefepime, each with and without clavulanic acid. Repetitive patient isolates and K1 hyperproducing Klebsiella oxytoca were excluded. To determine the molecular types, PCR amplifying SHV, TEM, and CTX-M genes was performed and amplicons were sequenced. Minimal inhibitory concentrations (MICs) of ertapenem were determined by Etest and interpreted according to the standards of CLSI. Results: Among 8,384 isolates screened, 57 (0.68%) phenotypically confirmed ESBLs were identified. The ESBL rate was 1.1% and 3.4% in Escherichia coli and Klebsiella pneumoniae, respectively. Among ESBL strains, 59.6% were E. coli, 31.6% K. pneumoniae, and 8.8% other genera. The majority (49.1%) of ESBL strains was found in urine samples. PCR and DNA sequencing analysis demonstrated that 61.4% of the ESBL strains expressed a CTX-M type, 15.8% an SHV ESBL type, and 5.3% a TEM ESBL type. CTX-M-15 was the predominant (29.8%) b-lactamase followed by CTX-M-3 and SHV-12. There was no epidemiological and microbiological evidence for an outbreak situation. In 9 strains, no CTX-M, SHV or TEM ESBL could be detected. The MIC 50 and MIC 90 of ertapenem were 0.06 mg/l and 0.25 mg/l, respectively. Overall, 98.2% of the strains were susceptible to ertapenem (MIC 2 mg/l). Conclusions: Despite an extensive screening strategy, the prevalence of ESBLs is low in our medical institution. The distribution of the ESBL types is similar to the distribution in institutions with high ESBL prevalence, being CTX-M the predominant ESBL class. The new compound ertapenem is highly active against the ESBL-producing Enterobacteriaceae tested.

Frontiers in Marine Science, 2020

Viral infections are one of the main human health problems in recent decades and the cancer remai... more Viral infections are one of the main human health problems in recent decades and the cancer remains one of the most lethal diseases worldwide. The development of new antiviral drugs for the treatment of human adenovirus (HAdV) infections continues to be a challenging goal for medicinal chemistry. There is no specific antiviral drug approved to treat infections caused by HAdV so far and the off-label treatments currently available show great variability in their effectiveness. In relation to cancer, most of the available drugs are designed to act on specific targets by altering the activity of involved transporters and genes. Taking into account the high antiviral and antiproliferative activity against tumor cell lines displayed by some marine natural products reported in the literature, sixty five marine organisms were selected: 51 sponges (Porifera), 13 ascidians (Chordata), and 1 gorgonian (Cnidaria), collected from Yucatan Peninsula, Mexico, to evaluate their antiviral activity against human adenovirus type 5 (HAdV5) and their anticancer properties against five human tumor cell lines, namely human lung carcinoma (A549), human skin melanoma (A2058), hepatocyte carcinoma (HepG2), breast adenocarcinoma (MCF7), and pancreas carcinoma (MiaPaca-2). Eleven extracts displayed anti-HAdV activity being the organic extracts of Dysidea sp., Agelas citrina, Chondrilla sp., Spongia tubulifera, and Monanchora arbuscula the five most active ones. On the other hand, 24 extracts showed antiproliferative activity against at least one tumor cell line, being the extracts of the ascidian Eudistoma amanitum and the sponge Haliclona (Rhizoniera) curacaoensis the most active ones. This work constitutes the first wide antiviral and antiproliferative screening report of extracts from the marine sponges, ascidians, and a gorgonian collected from the Yucatan Peninsula, Mexico.

Journal of Infection

Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on ... more Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre-including this research content-immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

Trabajo presentado en el 2nd AdenoNet Meeting of the Spanish Adenovirus Network, celebrado en Bar... more Trabajo presentado en el 2nd AdenoNet Meeting of the Spanish Adenovirus Network, celebrado en Barcelona (Espana) del 5 al 6 de octubre de 2017.

Scientific Reports, 2021

The aim was to assess the ability of nasopharyngeal SARS-CoV-2 viral load at first patient’s hosp... more The aim was to assess the ability of nasopharyngeal SARS-CoV-2 viral load at first patient’s hospital evaluation to predict unfavorable outcomes. We conducted a prospective cohort study including 321 adult patients with confirmed COVID-19 through RT-PCR in nasopharyngeal swabs. Quantitative Synthetic SARS-CoV-2 RNA cycle threshold values were used to calculate the viral load in log10 copies/mL. Disease severity at the end of follow up was categorized into mild, moderate, and severe. Primary endpoint was a composite of intensive care unit (ICU) admission and/or death (n = 85, 26.4%). Univariable and multivariable logistic regression analyses were performed. Nasopharyngeal SARS-CoV-2 viral load over the second quartile (≥ 7.35 log10 copies/mL, p = 0.003) and second tertile (≥ 8.27 log10 copies/mL, p = 0.01) were associated to unfavorable outcome in the unadjusted logistic regression analysis. However, in the final multivariable analysis, viral load was not independently associated wit...

Motivation: Ebola virus (EBOV) is considered as the prototypical pathogen of viral hemorrhagic fe... more Motivation: Ebola virus (EBOV) is considered as the prototypical pathogen of viral hemorrhagic fever, causing severe disease and mortality rates as high as 90%. The implementation of different High-Throughput Screening systems to avoid the use of BSL-4 facilities will promote the generation of lead molecules and so the development of new therapeutics for EBOV within the next few years. The goals of the present project are directed to the discovery of new antiviral drugs against EBOV by using HTS of different libraries of small compounds, some of which have previously been an excellent source of potent antiviral compounds, by the use of a retroviral pseudotype particle (pEBOV-GFP) carrying the EBOV glycoprotein (GP). Methods: Retroviral pseudotypes were generated by the transfection with the HIV gag-pol plasmid, pCMV-Δ8.91, the EBOV GP expression construct, pCAGGS-EBOV, and the green fluorescence protein (GFP) reporter construct, pCSGW at a ratio of 1.1:0.5:0.75 (core✉️report...

Cellular & Molecular Immunology, 2021

Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection induces an exacerbated infla... more Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection induces an exacerbated inflammation driven by innate immunity components. Dendritic cells (DCs) play a key role in the defense against viral infections, for instance plasmacytoid DCs (pDCs), have the capacity to produce vast amounts of interferon-alpha (IFN-α). In COVID-19 there is a deficit in DC numbers and IFNα production, which has been associated with disease severity. In this work, we described that in addition to the DC deficiency, several DC activation and homing markers were altered in acute COVID-19 patients, which were associated with multiple inflammatory markers. Remarkably, previously hospitalized and nonhospitalized patients remained with decreased numbers of CD1c+ myeloid DCs and pDCs seven months after SARS-CoV-2 infection. Moreover, the expression of DC markers such as CD86 and CD4 were only restored in previously nonhospitalized patients, while no restoration of integrin β7 and indoleamine 2,3-dyoxigenase (IDO) levels were observed. These findings contribute to a better understanding of the immunological sequelae of COVID-19.

PLOS ONE, 2021

The aim was to analyze the characteristics and predictors of unfavorable outcomes in solid organ ... more The aim was to analyze the characteristics and predictors of unfavorable outcomes in solid organ transplant recipients (SOTRs) with COVID-19. We conducted a prospective observational cohort study of 210 consecutive SOTRs hospitalized with COVID-19 in 12 Spanish centers from 21 February to 6 May 2020. Data pertaining to demographics, chronic underlying diseases, transplantation features, clinical, therapeutics, and complications were collected. The primary endpoint was a composite of intensive care unit (ICU) admission and/or death. Logistic regression analyses were performed to identify the factors associated with these unfavorable outcomes. Males accounted for 148 (70.5%) patients, the median age was 63 years, and 189 (90.0%) patients had pneumonia. Common symptoms were fever, cough, gastrointestinal disturbances, and dyspnea. The most used antiviral or host-targeted therapies included hydroxychloroquine 193/200 (96.5%), lopinavir/ritonavir 91/200 (45.5%), and tocilizumab 49/200 (2...

ACS Infectious Diseases, 2020

Over the years, human adenovirus (HAdV) has progressively been recognized as a significant viral ... more Over the years, human adenovirus (HAdV) has progressively been recognized as a significant viral pathogen. Traditionally associated with self-limited respiratory, gastrointestinal, and conjunctival infections, mainly in immunocompromised patients, HAdV is currently considered to be a pathogen presenting significant morbidity and mortality in both immunosuppressed and otherwise healthy individuals. Currently available therapeutic options are limited because of their lack of effectivity and related side effects. In this context, there is an urgent need to develop effective anti-HAdV drugs with suitable therapeutic indexes. In this work, we identified new serinol-derived benzoic acid esters as novel scaffolds for the inhibition of HAdV infections. A set of 38 compounds were designed and synthesized, and their antiviral activity and cytotoxicity were evaluated. Four compounds (13, 14, 27, and 32) inhibited HAdV infection at low micromolar concentrations (2.82-5.35 μM). Their half maximal inhibitory concentration (IC50) values were lower compared to that of cidofovir, the current drug of choice. All compounds significantly reduced the HAdV DNA replication process, while they did not block any step of the viral entry. Our results showed that compounds 13, 14, and 32 seem to be targeting the expression of the E1A early gene. Moreover, all four derivatives demonstrated a significant inhibition of human cytomegalovirus (HCMV) DNA replication. This new scaffold may represent a potential tool useful for the development of effective anti-HAdV drugs.

Journal of Infection, 2021

International Journal of Antimicrobial Agents, 2020

In vitro co-infection by cytomegalovirus improves the antiviral activity of ganciclovir against h... more In vitro co-infection by cytomegalovirus improves the antiviral activity of ganciclovir against human adenovirus,

Bioorganic & Medicinal Chemistry Letters, 2020

Higher Learning Institutions today are increasingly required to produce highly mobile graduates a... more Higher Learning Institutions today are increasingly required to produce highly mobile graduates able to respond to the ever changing needs of the contemporary workplace. Through industrial training, interns will be exposed to ethical values and good working practices as well as to help them understand the safety practices and regulations inside the industry and to instill the spirit of teamwork and good relationship between interns and employees. The motivation for the current research study is to examine the implementation of industrial training conducted by Faculty of Business and Management of Universiti Teknologi MARA and industrial perception on Business Students during their practical period. This research is also prompted by the concern in the increasing number of unemployed among fresh graduates. Feedback from industries would give a better picture of what is required of students since employers are increasingly looking beyond a graduate's academic knowledge. Results show that interns are flexible towards task assigned, committed and resourceful towards work. However, their level of problem solving and analytical skills were low and they also lacked communication skills. It is anticipated that this exploratory study will enable the academia to bridge the gap between theory and practice thus improving the curricula towards developing successful professional business graduates.

Haematologica, 2020

T-cells immune response controls the high incidence of adenovirus infection in adult allogenic he... more T-cells immune response controls the high incidence of adenovirus infection in adult allogenic hematopoietic transplantation recipients.