Anticuerpos anti-SARS-CoV-2 en personal de salud de un hospital pediátrico / SARS-CoV-2 antibodies among health care workers from a children's hospital

Introducción. En Argentina, el personal de salud ha sido el primero en vacunarse contra COVID-19, pero todavía existen pocos datos sobre la producción de anticuerpos IgG anti-S. Objetivos. Evaluar IgG específica contra glicoproteína spike del SARS-CoV-2 (IgG anti-S) posvacunación en personal de un hospital pediátrico. Explorar la asociación entre presencia de dichos anticuerpos, edad y antecedente de infección previa. Población y métodos. Estudio transversal que incluyó 193 trabajadores vacunados con los dos componentes de la vacuna Sputnik V. Se pesquisó el título de IgG anti-S y se registraron edad, antecedente de infección previa por SARS-CoV-2 y fecha de la vacunación. Resultados. El 98,6 % de los sujetos generó IgG anti-S. El título fue mayor en quienes habían cursado infección previamente (p <0,001), pero no hubo relación con la edad de los sujetos. Conclusión. Aportamos datos de generación de anticuerpos IgG anti-S posvacunación en personal de salud de un hospital pediátrico y exploramos algunos predictores.

Introduction. In Argentina, health care workers have been the first ones to receive the COVID-19 vaccine, but there are still few data on the production of anti-S IgG antibodies. Objectives. To assess specific IgG against the SARS-CoV-2 spike protein (anti-S IgG) after the vaccination of health care workers from a children's hospital. To explore the association between the presence of these antibodies, age, and history of prior infection. Population and methods. Cross-sectional study in 193 workers who received both doses of the two component Sputnik V vaccine. The anti-S IgG antibody titer was measured and age, history of prior SARS-CoV-2 infection, and date of vaccination were recorded. Results. Anti-S IgG antibodies were produced in 98.6% of the subjects. The titer was higher in those with prior infection (p < 0.001), but no relationship was established with subjects' age. Conclusion. We provide data on post-vaccination production of IgG anti-S antibodies among health care workers from a children's hospital and explore some predictors.

La variante SARS-CoV-2 ómicron / SARS-CoV-2 omicron variant

Introducción: A finales de noviembre de 2021, la Organización Mundial de la Salud (OMS) designó a la cepa conocida como B.1.1.529 como una variante de preocupación y le otorgó la designación ómicron, con lo cual se convierte en la cuarta variante de preocupación enumerada, junto con las variantes alfa, beta, gamma y delta. El propósito de este estudio es presentar información de la aparición, características y algunos datos de la variante ómicron. Conclusiones: Las deficientes infraestructuras en los sistemas de salud que hay en nuestro país, la baja tasa de vacunación y la presencia de comorbilidades e inmunodeficiencia en la población inducen a que ésta sea más susceptible a la infección de estas nuevas variantes. Se requiere un esfuerzo global del gobierno, las industrias farmacéuticas/biotecnológicas y las instituciones académicas y sanitarias para contener eficazmente esta pandemia (AU)

Introduction: In late November 2021, the World Health Organization (WHO) designated the strain known as B.1.1.529 as a variant of concern, and granted it the omicron designation, making it the fourth variant of concern listed along with alpha, beta, gamma, and delta variants. The purpose of the study is to present information on the occurrence, characteristics and some data on the omicron variant. Conclusions: The deficient health infrastructures present in our country, the low vaccination rate and the presence of population with comorbidities and immunodeficiency or both, are more susceptible to infection to these new variants. A global effort by the government, pharmaceutical/biotechnology industries, and academic and health institutions is required to effectively contain this pandemic (AU)

Bioactive compounds of Jingfang Granules against SARS-CoV-2 virus proteases 3CLpro and PLpro / 北京大学学报(医学版)

OBJECTIVE@#Jingfang Granules have been recommended for the prevention and treatment of corona virus disease 2019 (COVID-19). Through chemical analysis and bioactivity evaluation, this study aims to elucidate the potential effective components of Jingfang Granules.@*METHODS@#The inhibitory acti-vities of Jingfang Granules extract against 3-chymotrypsin-like protease (3CLpro), papain like protease (PLpro), spike protein receptor-binding domain (S-RBD) and human cyclooxygenase-2 (COX-2) were evaluated using enzyme assay. The antitussive effects were evaluated using the classical ammonia-induced cough model. The chemical constituents of Jingfang Granules were qualitatively and quantitatively analyzed by liquid chromatography-mass spectrometry (LC/MS). The 3CLpro and PLpro inhibitory activities of the major compounds were determined by enzyme assay, molecular docking, and site-directed mutagenesis.@*RESULTS@#Jingfang Granules exhibited 3CLpro and PLpro inhibitory activities, as well as COX-2 inhibitory and antitussive activities. By investigating the MS/MS behaviors of reference standards, a total of fifty-six compounds were characterized in Jingfang Granules. Sixteen of them were unambiguously identified by comparing with reference standards. The contents of the 16 major compounds were also determined, and their total contents were 2 498.8 μg/g. Naringin, nodakenin and neohesperidin were three dominating compounds in Jingfang Granules, and their contents were 688.8, 596.4 and 578.7 μg/g, respectively. In addition, neohesperidin and naringin exhibited PLpro inhibitory activities, and the inhibition rates at 8 μmol/L were 53.5% and 46.1%, respectively. Prim-O-glucosylcimifugin showed significant inhibitory activities against 3CLpro and PLpro, and the inhibitory rates at 8 μmol/L were 76.8% and 78.2%, respectively. Molecular docking indicated that hydrogen bonds could be formed between prim-O-glucosylcimifugin and amino acid residues H163, E166, Q192, T190 of 3CLpro (binding energy, -7.7 kcal/mol) and K157, D164, R166, E167, T301 of PLpro(-7.3 kcal/mol), respectively. Site-directed mutagenesis indicated amino acid residue K157 was a key active site for the interaction between prim-O-glucosylcimifugin and PLpro.@*CONCLUSION@#Prim-O-glucosylcimifugin, neohesperidin, and naringin as the major compounds from Jingfang Granules could inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus proteases 3CLpro and PLpro. The results are valuable for rational clinical use of Jingfang Granules.

An ultrapotent pan-β-coronavirus lineage B (β-CoV-B) neutralizing antibody locks the receptor-binding domain in closed conformation by targeting its conserved epitope

New threats posed by the emerging circulating variants of SARS-CoV-2 highlight the need to find conserved neutralizing epitopes for therapeutic antibodies and efficient vaccine design. Here, we identified a receptor-binding domain (RBD)-binding antibody, XG014, which potently neutralizes β-coronavirus lineage B (β-CoV-B), including SARS-CoV-2, its circulating variants, SARS-CoV and bat SARSr-CoV WIV1. Interestingly, antibody family members competing with XG014 binding show reduced levels of cross-reactivity and induce antibody-dependent SARS-CoV-2 spike (S) protein-mediated cell-cell fusion, suggesting a unique mode of recognition by XG014. Structural analyses reveal that XG014 recognizes a conserved epitope outside the ACE2 binding site and completely locks RBD in the non-functional "down" conformation, while its family member XG005 directly competes with ACE2 binding and position the RBD "up". Single administration of XG014 is effective in protection against and therapy of SARS-CoV-2 infection in vivo. Our findings suggest the potential to develop XG014 as pan-β-CoV-B therapeutics and the importance of the XG014 conserved antigenic epitope for designing broadly protective vaccines against β-CoV-B and newly emerging SARS-CoV-2 variants of concern.

Progress on the development of the SARS-CoV-2 vaccine and antibody drugs / 生物医学工程学杂志

The raging global epidemic of coronavirus disease 2019 (COVID-19) not only poses a major threat to public health, but also has a huge impact on the global health care system and social and economic development. Therefore, accelerating the development of vaccines and antibody drugs to provide people with effective protection and treatment measures has become the top priority of researchers and medical institutions in the field. At present, several vaccines and antibody drugs targeting SARS-Cov-2 have been in the stage of clinical research or approved for marketing around the world. In this manuscript, we summarized the vaccines and antibody drugs which apply genetic engineering technologies to target spike protein, including subunit vaccines, viral vector vaccines, DNA vaccines, mRNA vaccines, and several neutralizing antibody drugs, and discussed the trends of vaccines and antibody drugs in the future.

Seasonal coronaviruses and SARS-CoV-2: effects of preexisting immunity during the COVID-19 pandemic / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Although the coronavirus disease 2019 (COVID-19) epidemic is still ongoing, vaccination rates are rising slowly and related treatments and drugs are being developed. At the same time, there is increasing evidence of preexisting immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in humans, mainly consisting of preexisting antibodies and immune cells (including T cells and B cells). The presence of these antibodies is mainly due to the seasonal prevalence of four common coronavirus types, especially OC43 and HKU1. The accumulated relevant evidence has suggested that the target of antibodies is mainly the S2 subunit of S protein, followed by evolutionary conservative regions such as the nucleocapsid (N) protein. Additionally, preexisting memory T and B cells are also present in the population. Preexisting antibodies can help the body protect against SARS-CoV-2 infection, reduce the severity of COVID-19, and rapidly increase the immune response post-infection. These multiple effects can directly affect disease progression and even the likelihood of death in certain individuals. Besides the positive effects, preexisting immunity may also have negative consequences, such as antibody-dependent enhancement (ADE) and original antigenic sin (OAS), the prevalence of which needs to be further established. In the future, more research should be focused on evaluating the role of preexisting immunity in COVID-19 outcomes, adopting appropriate policies and strategies for fighting the pandemic, and vaccine development that considers preexisting immunity.

Preparation and immungenicity of recombinant protein containing intramolecular adjuvant in SARS-CoV-2 RBD domain / 生物工程学报

A fusion protein containing a tetanus toxin peptide, a tuftsin peptide and a SARS-CoV-2S protein receptor-binding domain (RBD) was prepared to investigate the effect of intramolecular adjuvant on humoral and cellular immunity of RBD protein. The tetanus toxin peptide, tuftsin peptide and S protein RBD region were connected by a flexible polypeptide, and a recombinant vector was constructed after codon optimization. The recombinant S-TT-tuftsin protein was prepared by prokaryotic expression and purification. BALB/c mice were immunized after mixed with aluminum adjuvant, and the humoral and cellular immune effects were evaluated. The recombinant S-TT-tuftsin protein was expressed as an inclusion body, and was purified by ion exchange chromatography and renaturated by gradient dialysis. The renaturated protein was identified by Dot blotting and reacted with serum of descendants immunized with SARS-CoV-2 subunit vaccine. The results showed that the antibody level reached a plateau after 35 days of immunization, and the serum antibody ELISA titer of mice immunized with recombinant protein containing intramolecular adjuvant was up to 1:66 240, which was significantly higher than that of mice immunized with S-RBD protein (P < 0.05). At the same time, the recombinant protein containing intramolecular adjuvant stimulated mice to produce a stronger lymphocyte proliferation ability. The stimulation index was 4.71±0.15, which was significantly different from that of the S-RBD protein (1.83±0.09) (P < 0.000 1). Intramolecular adjuvant tetanus toxin peptide and tuftsin peptide significantly enhanced the humoral and cellular immune effect of the SARS-CoV-2 S protein RBD domain, which provideda theoretical basis for the development of subunit vaccines for SARS-CoV-2 and other viruses.

SARS-CoV-2 neutralizing monoclonal antibodies and nanobodies: a review / 生物工程学报

Coronavirus disease (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), with strong contagiousness, high susceptibility and long incubation period. cell entry by SARS-CoV-2 requires the binding between the receptor-binding domain of the viral spike protein and the cellular angiotensin-converting enzyme 2 (ACE2). Here, we briefly reviewed the mechanisms underlying the interaction between SARS-CoV-2 and ACE2, and summarized the latest research progress on SARS-CoV-2 neutralizing monoclonal antibodies and nanobodies, so as to better understand the development process and drug research direction of COVID-19. This review may facilitate understanding the development of neutralizing antibody drugs for emerging infectious diseases, especially for COVID-19.

Glycosylation, glycan receptors recognition of SARS-CoV-2 and discoveries of glycan inhibitors against SARS-CoV-2 / 生物工程学报

COVID-19 represents the most serious public health event in the past few decades of the 21st century. The development of vaccines, neutralizing antibodies, and small molecule chemical agents have effectively prevented the rapid spread of COVID-19. However, the continued emergence of SARS-CoV-2 variants have weakened the efficiency of these vaccines and antibodies, which brought new challenges for searching novel anti-SARS-CoV-2 drugs and methods. In the process of SARS-CoV-2 infection, the virus firstly attaches to heparan sulphate on the cell surface of respiratory tract, then specifically binds to hACE2. The S protein of SARS-CoV-2 is a highly glycosylated protein, and glycosylation is also important for the binding of hACE2 to S protein. Furthermore, the S protein is recognized by a series of lectin receptors in host cells. These finding implies that glycosylation plays important roles in the invasion and infection of SARS-CoV-2. Based on the glycosylation pattern and glycan recognition mechanisms of SARS-CoV-2, it is possible to develop glycan inhibitors against COVID-19. Recent studies have shown that sulfated polysaccharides originated from marine sources, heparin and some other glycans display anti-SARS-CoV-2 activity. This review summarized the function of glycosylation of SARS-CoV-2, discoveries of glycan inhibitors and the underpinning molecular mechanisms, which will provide guidelines to develop glycan-based new drugs against SARS-CoV-2.

Seguridad de las vacunas contra la COVID-19 / COVID-19 vaccine safety

RESUMEN El desarrollo y producción de vacunas seguras y eficaces contra la enfermedad por coronavirus 2019 (COVID-19) ofrece la esperanza para el control de la pandemia actual. Los eventos adversos posteriores a la inmunización son respuestas indeseadas o acontecimientos involuntarios que siguen a la vacunación, y que deben ser cuidadosamente vigilados, ya que todas las vacunas, incluyendo las desarrolladas contra el SARS-CoV-2, requieren cumplir con los criterios de seguridad para su administración en humanos. Se recopiló la información de la base de datos de PubMed/Medline durante los meses de agosto de 2020 a noviembre de 2021. La mayoría de los eventos adversos identificados en los ensayos clínicos fueron leves o moderados; sin embargo, se identificaron eventos trombóticos asociados a algunas vacunas basadas en vectores virales contra la COVID-19 en estudios de seguimiento, aunque se requiere la conclusión de los distintos estudios en curso y vigilancia poscomercialización para determinar todos los posibles eventos adversos y de especial interés.

ABSTRACT The development and production of safe and effective vaccines against coronavirus disease 2019 (COVID-19) provides hope for controlling the current pandemic. Adverse events following immunization are unwanted responses or unintended events that must be carefully monitored, as all vaccines, including those developed against SARS-CoV-2, are required to meet safety criteria for administration in humans. Information was collected from the PubMed/Medline database during the months of August 2020 to November 2021. Most adverse events reported in clinical trials were mild or moderate; however, thrombotic events associated with some viral vector-based vaccines against COVID-19 were identified in follow-up studies, although completion of the various ongoing studies and post-marketing surveillance is required to determine all potential adverse events, as well as those of special interest.

Proteína de la espícula del virus SARS-CoV-2 y su relación con la enzima convertidora de angiotensina-2 / Proteína de pico do vírus SARS-CoV-2 e sua relação com a enzima conversora de angiotensina-2 / Spike protein of the SARS-CoV-2 virus and its relationship with the angiotensin-converting enzyme-2

Introducción: La COVID-19 causada por el virus del SARS-CoV-2 es una pandemia que ha cobrado la vida de millones de personas y sobrecargado los servicios sanitarios de todo el mundo. Objetivo: Describir la relación entre la proteína de la espícula (proteína S, proteína espicular o spike) del SARS-CoV-2 y enzima convertidora de angiotensina 2 como desencadenante primario de la infección por la COVID-19. Método: Se realizó una búsqueda bibliográfica en Google Académico, SciELO y PubMed, con los descriptores iniciales COVID-19 y SARS-CoV-2. El periodo de publicación seleccionado fue entre los años 2019-2021, sin restricciones en cuanto al tipo de artículo. Los trabajos debieron estar disponibles en español e inglés a texto completo. Resultados: La proteína de la espícula del SARS-CoV-2, que desempeña un papel clave en el reconocimiento del receptor y en el proceso de fusión de la membrana celular, está compuesta por dos subunidades, S1 y S2. La subunidad S1 contiene un dominio de unión al receptor RBD (por sus siglas en inglés, receptor-binding domain) que se une al receptor del huésped, la enzima convertidora de angiotensina 2, mientras que la subunidad S2 interviene en la fusión de la membrana viral y celular. La ubicuidad tisular de la enzima convertidora de angiotensina 2 explica las múltiples manifestaciones clínicas de la enfermedad. Conclusiones: El conocimiento de la relación entre el SARS-CoV-2 y su receptor enzima convertidora de angiotensina 2 permite no solo conocer la fisiopatología de la COVID-19, sino el diseño de fármacos antivirales y vacunas que contribuyen a la prevención y tratamiento de esta enfermedad viral.

Introduction: COVID-19 caused by the SARS-CoV-2 virus is a pandemic that has claimed the lives of millions of people and overloaded health services around the world. Objective: To describe the relationship between the spike protein (S) of SARS-CoV-2 and the angiotensin-converting enzyme 2 as the primary trigger of COVID-19 infection. Method: A bibliographic search was carried out in Google Scholar, SciELO and PubMed, with the initial descriptors COVID-19 and SARS-CoV-2. The publication period selected was between the years 2019 to 2021, without restrictions regarding the type of article. The papers had to be available in full text in Spanish and English. Results: The spike protein of SARS-CoV-2, which plays a key role in receptor recognition and in the cell membrane fusion process, is composed of two subunits, S1 and S2. The S1 subunit contains a receptor-binding domain (RBD) that binds to the host's receptor, angiotensin-converting enzyme 2, while the S2 subunit is involved in the viral and cellular membrane fusion. The tissue ubiquity of angiotensin converting enzyme 2 explains the multiple clinical manifestations of the disease. Conclusions: The knowledge of the relationship between SARS-CoV-2 and its receptor the angiotensin-converting enzyme 2, allows not only to know the pathophysiology of COVID-19, but also the design of antiviral drugs and vaccines that contribute to the prevention and treatment of this viral disease.

Introdução: COVID-19 causada pelo vírus SARS-CoV-2 é uma pandemia que ceifou a vida de milhões de pessoas e sobrecarregou os serviços de saúde em todo o mundo. Objetivo: Descrever a relação entre a proteína spike (S) do SARS-CoV-2 e a enzima conversora de angiotensina 2 como o principal fator desencadeante da infecção por COVID-19. Método: Foi realizada uma busca bibliográfica no Google Scholar, SciELO e PubMed, com os descritores iniciais COVID-19 e SARS-CoV-2. O período de publicação selecionado foi entre os anos de 2019 a 2021, sem restrições quanto ao tipo de artigo. Os artigos deveriam estar disponíveis na íntegra em espanhol e inglês. Resultados: A proteína spike do SARS-CoV-2, que desempenha um papel fundamental no reconhecimento do receptor e no processo de fusão da membrana celular, é composta por duas subunidades, S1 e S2. A subunidade S1 contém um domínio de ligação ao receptor (RBD) que se liga ao receptor do hospedeiro, a enzima conversora de angiotensina 2, enquanto a subunidade S2 está envolvida na fusão da membrana viral e celular. A onipresença tecidual da enzima conversora da angiotensina 2 explica as múltiplas manifestações clínicas da doença. Conclusões: O conhecimento da relação entre o SARS-CoV-2 e seu receptor, a enzima conversora de angiotensina 2, permite não só conhecer a fisiopatologia da COVID-19, mas também o desenho de antivirais e vacinas que contribuam para a prevenção e tratamento desta doença viral.

The impact of spike mutated variants of SARS-CoV2 [Alpha, Beta, Gamma, Delta, and Lambda] on the efficacy of subunit recombinant vaccines

ABSTRACT Since the first described human infection with SARS-CoV-2 in December of 2019 many subunit protein vaccines have been proposed for use in humans. Subunit vaccines use one or more antigens suitable for eliciting a robust immune response. However, the major concern is the efficacy of subunit vaccines and elicited antibodies to neutralize the variants of SARS-CoV-2 like B.1.1.7 (Alpha), B.1.351 (Beta) and P1 (Gamma), B.1.617 (Delta) and C.37 (Lambda). The Spike protein (S) is a potential fragment for use as an antigen in vaccine development. This protein plays a crucial role in the first step of the infection process, as it binds to Angiotensin-Converting Enzyme 2 (ACE2) receptor and enters the host cell after binding. Immunization-induced specific antibodies against the receptor binding domain (RBD) may block and effectively prevent virus invasion. The focus of this review is the impact of spike mutated variants of SARS-CoV2 (Alpha, Beta, Gamma, Delta, and Lambda) on the efficacy of subunit recombinant vaccines. To date, a low or no significant impact on vaccine efficacy against Alpha and Delta variants has been reported. Such an impact on vaccine efficacy for Beta, Delta, Gamma, and Lambda variants may be even greater compared to the Alpha variant. Nonetheless, more comprehensive analyses are needed to assess the real impact on vaccine efficacy brought about by SARS-CoV-2 variants.

SARS-CoV-2 recombinant proteins stimulate distinct cellular and humoral immune response profiles in samples from COVID-19 convalescent patients

OBJECTIVES: In this preliminary study we investigated cellular and humoral immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens in blood samples from 14 recovered coronavirus disease 2019 (COVID-19) patients and compared them to those in samples from 12 uninfected/unvaccinated volunteers. METHODS: Cellular immunity was assessed by intracellular detection of IFN-γ in CD3+ T lymphocytes after stimulation with SARS-CoV-2 spike (S1), nucleocapsid (NC), or receptor-binding domain (RBD) recombinant proteins or overlapping peptide pools covering the sequence of SARS-CoV-2 spike, membrane and nucleocapsid regions. The humoral response was examined by ELISAs and/or chemiluminescence assays for the presence of serum IgG antibodies directed to SARS-CoV-2 proteins. RESULTS: We observed differences between humoral and cellular immune profiles in response to stimulation with the same proteins. Assays of IgG antibodies directed to SARS-CoV-2 NC, RBD and S1/S2 recombinant proteins were able to differentiate convalescent from uninfected/unvaccinated groups. Cellular immune responses to SARS-CoV-2 protein stimuli did not exhibit a specific response, as T cells from both individuals with no history of contact with SARS-CoV-2 and from recovered donors were able to produce IFN-γ. CONCLUSIONS: Determination of the cellular immune response to stimulation with a pool of SARS-CoV-2 peptides but not with SARS-CoV-2 proteins is able to distinguish convalescent individuals from unexposed individuals. Regarding the humoral immune response, the screening for serum IgG antibodies directed to SARS-CoV-2 proteins has been shown to be specific for the response of recovered individuals.

Seroprevalence of IgM and IgG Antibodies against SARS-CoV-2 in Asymptomatic People in Wuhan: Data from a General Hospital Near South China Seafood Wholesale Market during March to April in 2020 / 生物医学与环境科学（英文）

The aim of this study was to estimate the seroprevalence of immunoglobulin M (IgM) and G (IgG) antibodies against SARS-CoV-2 in asymptomatic people in Wuhan. This was a cross-sectional study, which enrolled 18,712 asymptomatic participants from 154 work units in Wuhan. Pearson Chi-square test,

Neutralizing monoclonal antibodies present new prospects to treat SARS-CoV-2 infections / 医学前沿

The coronavirus disease 2019 (COVID-19) has caused global public health and economic crises. Thus, new therapeutic strategies and effective vaccines are urgently needed to cope with this severe pandemic. The development of a broadly neutralizing antibody against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is one of the attractive treatment strategies for COVID-19. Currently, the receptor-binding domain (RBD) of the spike (S) protein is the main target of neutralizing antibodies when SARS-CoV-2 enters human cells through an interaction between the S protein and the angiotensin-converting enzyme 2 expressed on various human cells. A single monoclonal antibody (mAb) treatment is prone to selective pressure due to increased possibility of targeted epitope mutation, leading to viral escape. In addition, the antibody-dependent enhancement effect is a potential risk of enhancing the viral infection. These risks can be reduced using multiple mAbs that target nonoverlapping epitopes. Thus, a cocktail therapy combining two or more antibodies that recognize different regions of the viral surface may be the most effective therapeutic strategy.

Degradation of SARS-CoV-2 receptor ACE2 by the E3 ubiquitin ligase Skp2 in lung epithelial cells / 医学前沿

An unexpected observation among the COVID-19 pandemic is that smokers constituted only 1.4%-18.5% of hospitalized adults, calling for an urgent investigation to determine the role of smoking in SARS-CoV-2 infection. Here, we show that cigarette smoke extract (CSE) and carcinogen benzo(a)pyrene (BaP) increase ACE2 mRNA but trigger ACE2 protein catabolism. BaP induces an aryl hydrocarbon receptor (AhR)-dependent upregulation of the ubiquitin E3 ligase Skp2 for ACE2 ubiquitination. ACE2 in lung tissues of non-smokers is higher than in smokers, consistent with the findings that tobacco carcinogens downregulate ACE2 in mice. Tobacco carcinogens inhibit SARS-CoV-2 spike protein pseudovirions infection of the cells. Given that tobacco smoke accounts for 8 million deaths including 2.1 million cancer deaths annually and Skp2 is an oncoprotein, tobacco use should not be recommended and cessation plan should be prepared for smokers in COVID-19 pandemic.

COVID-19 y la pandemia global causada por un nuevo coronavirus / COVID-19 and the global pandemic caused by a new coronavirus

Resumen Introducción: OVID-19 es una enfermedad respiratoria inédita que se reportó inicialmente como una neumonía atípica en diciembre de 2019. SARS-CoV-2, agente etiológico de esta patología, probablemente originado a partir de un virus de murciélago. La inesperada capacidad de transmisión y patogenicidad que adquirió este coronavirus transformó a COVID-19 en una pandemia de sintomatología variada y compleja. Objetivo: Analizar aspectos evolutivos, moleculares, biológicos, inmunológicos y epidemiológicos de esta enfermedad. Materiales y métodos: Se realizó una revisión narrativa de literatura científica publicada en Pubmed, sobre estos aspectos desde enero 2020. Resultados: SARS-CoV-2 es un nuevo coronavirus que utiliza su proteína superficial S para infectar células humanas que exhiben el receptor ACE2. Este patógeno se transmite por secreciones respiratorias e induce un incremento nocivo de mediadores químicos proinflamatorios en individuos vulnerables, reacción inmune conocida como tormenta de citoquinas. Esta respuesta hiper-inflamatoria es la causante de las lesiones alveolares que desencadenan la insuficiencia respiratoria observada en casos severos de COVID-19. Conclusiones: En individuos susceptibles, SARS-CoV-2 puede desencadenar una disfunción pulmonar que requiere soporte ventilatorio asistido y tratamiento con inmunosupresores. Se están desarrollando nuevas estrategias terapéuticas y de prevención para disminuir los elevados índices de contagio y la mortalidad asociados con COVID-19.

Abstract Introduction: COVID-19 is a new respiratory disease reported initially as an atypical pneumonia in December 2019. SARS-CoV-2, the etiological agent of this pathology, probably originated from a bat viral pathogen. The unexpected transmission and pathogenicity capacities that this coronavirus acquired turned COVID-19 into a pandemic with a wide and complex arrangement of symptoms. Objective: To analyze evolutionary, molecular, biological, immunological and epidemiological aspects of this disease. Materials and methods: A narrative review of the literature concerning these topics was conducted, which was published in Pubmed mostly from January 2020. Results: SARS-CoV-2 is a new coronavirus that uses its surface protein S to infect human cells that exhibit ACE2 receptors. This pathogen is transmitted through respiratory secretions and triggers a harmful increase in pro-inflammatory chemical mediators in vulnerable individuals, an immune reaction known as cytokine storm. This hyper-inflammatory response is the cause of the alveolar lesions behind the respiratory failure observed in severe cases of COVID-19. Conclusions: In susceptible individuals, SARS-CoV-2 triggers an acute respiratory distress syndrome that requires assisted ventilatory support and immunomodulatory therapy. New therapeutic and prevention strategies are being developed to reduce the high transmission and mortality rates associated with COVID-19.

COVID-19. Opciones terapéuticas desde la viro-patogénesis a la evidencia clínica / COVID-19. Therapeutics options from the viro-pathogenesis to the clinical evidence

Resumen Cada vez sabemos más sobre este enemigo mortal de la familia de los Betacoronavirus, llamado inicialmente 19-nCoV, causante de la COVID-19 (Coronavirus infectous disease por su sigla en inglés), hoy clasificado SARS-CoV-2, porque es responsable de producir el SARS (síndrome respiratorio agudo severo, por sus siglas en inglés) y que comparte una fuerte homología de secuencia con el SARS-CoV, su primo hermano causante de la epidemia en 2003 del SARS, ambos capaces de diseminarse rápidamente, en particular este, y causar un gran caos mundial como ha sucedido con esta pandemia. Con base en estudios previos de focalización en el SARS-CoV, y también en el virus causante del MERS (síndrome respiratorio del Oriente Medio, por sus siglas en inglés), y con el conocimiento que se tiene actualmente sobre el SARS-CoV-2, se exploran en este artículo algunas opciones terapéuticas para el manejo de la infección por este virus complejo y con capacidad letal, mencionando algunos aspectos de relevancia patogénica. Se enfatizó en las posibles alternativas de manejo desde la fisiopatología y patogénesis hasta la evidencia actualmente disponible. Exploraremos el uso probable de ECA2 recombinante, algunas moléculas experimentales, revisaremos los antimaláricos (cloroquina e hidroxicloroquina), esteroides, azitromicina, antivirales específicos como remdesivir, lopinavir/ritonavir, biológicos como tocilizumab, anticuerpos monoclonales antivirales, y haremos énfasis en la trasfusión de plasma de convalecientes desde el principio de inmunización pasiva, de gran utilidad.

Abstract We know more and more about this deadly enemy of the Betacoronavirus family, initially called 19- nCoV that causes COVID-19 (Coronavirus infectous disease), today classified SARS-CoV-2, because it is responsible for producing SARS (severe acute respiratory syndrome), It shares a strong sequence homology with SARS-CoV, its cousin that caused the 2003 SARS epidemic, both capable of spreading rapidly, particularly this one and causing great global chaos as has happened with this pandemic. Based on previous studies targeting SARS-CoV, and also on the virus that causes MERS (Middle East Respiratory Syndrome); and with the current knowledge about SARS-CoV-2, we will explore some therapeutic options for the management of infection by this complex and lethal virus, mentioning some aspects of pathogenic relevance. Possible management alternatives from the pathophysiology and pathogenesis to the evidence currently available were emphasized. We will explore the probable use of ECA2 recombinate, some experimental molecules, we will review some of the antimalarials (chloroquine and hydroxychloroquine), steroids, azithromycin, specific antivirals such as remdesivir, lopinavir / ritonavir, biologics such as tocilizumab, monoclonal antiviral antibodies, and we will emphasize transfusion of convalescent plasma from the passive immunization principle, very useful.

Análisis de inmunogenicidad y perfil de seguridad de vacunas contra el SARS-CoV-2 en ensayos clínicos de fase I/II / Immunogenicity and safety profile analysis of SARS-CoV-2 vaccines in phase I/II clinical trials

The development of an effective vaccine against SARSCoV-2 has turned into a global priority in order to stop the advance of this ongoing COVID-19 pandemic. To date there are 25 candidate vaccines currently in a clinical trial stage, 3 of which have been subjected to phase I/II preliminary reports (ChAdOx1 nCoV-19, BNT162b1 and mRNA-1273). These vaccines have demonstrated to elicit robust cellular and humoral immune responses when compared to convalescent patients serum samples and have shown an acceptable safety profile with no reported severe side effects. Here we discuss the reported evidence regarding these vaccines.