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1.
J Infect Dis ; 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39132824

RESUMO

Reports have described SARS-CoV-2 rebound in COVID-19 patients treated with nirmatrelvir, a 3CL protease inhibitor. The cause remains a mystery, although drug resistance, re-infection, and lack of adequate immune responses have been excluded. We now present virologic findings that provide a clue to the cause of viral rebound, which occurs in ∼20% of the treated cases. Persistence of infectious SARS-CoV-2 was experimentally documented in vitro after treatment with nirmatrelvir or another 3CL protease inhibitor, but not with a polymerase inhibitor, remdesivir. This infectious form decayed slowly with a half-life of ∼1 day, suggesting that its persistence could outlive the treatment course to re-ignite SARS-CoV-2 infection as the drug is eliminated. Notably, extending nirmatrelvir treatment beyond 8 days abolished viral rebound in vitro. Our findings point in a particular direction for future investigation of virus persistence and offer a specific treatment recommendation that should be tested clinically.

2.
J Minim Access Surg ; 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38557406

RESUMO

INTRODUCTION: Endoscopic retrograde cholangiopancreatography (ERCP) facilitates the removal of common bile duct (CBD) calculi by endoscopy. When ERCP fails, exploration of CBD is required for the clearance of CBD calculi. The optimum way for the exploration of CBD is by choledochoscopy. Dedicated flexible or rigid choledochoscopes are expensive and available only in few places in India. Since 1991, we subjected patients with suspected CBD calculi to ERCP, followed by laparoscopic cholecystectomy (LC). Patients in whom ERCP failed to clear CBD were subjected to open exploration of CBD using any easily available, suitable, straight rigid scope for choledochoscopy. PATIENTS AND METHODS: Since March 1991, out of 8866 patients with cholelithiasis, 862 underwent ERCP. Ninety-six patients in whom ERCP failed to clear CBD underwent open exploration of CBD. In each case of exploration of CBD, choledochoscopy was performed using a straight rigid scope, either a cystoscope, paediatric cystoscope, hysteroscope or 5-mm laparoscopy telescope with a 5-mm cannula. RESULTS: The CBD clearance was complete in 95 patients, and one patient had an impacted calculus at the ampulla. CBD explorations were followed by choledochoduodenostomy, T-tube placement or suturing of choledochotomy. No residual calculi were observed after such exploration. CONCLUSION: From our results, we advocate the following algorithm for CBD calculi in resource-limited settings. Subject patients with CBD calculi to ERCP followed by LC. In case of failed ERCP, open exploration of CBD with choledochoscopy using any suitable rigid scope. Dedicated flexible or rigid choledochoscope is not essential. This approach is cost-effective and successful.

3.
Cureus ; 16(3): e56505, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38646396

RESUMO

Background Diabetes mellitus (DM) presents global challenges, with optimal glycemic control being pivotal in managing complications, notably in type 2 diabetes mellitus (T2DM). Yet, achieving sustained control faces barriers stemming from socioeconomic and gender-specific disparities. This study addresses these gaps by examining socioeconomic determinants and gender disparities in diabetes management, particularly in Maharashtra, India. Methodology This cross-sectional study involved 302 T2DM patients aged 20 to 79 years. Data on sociodemographic, behavioral, and clinical factors were collected through interviews, and records were analyzed via logistic regression to identify predictors of glycemic control. Results Significant associations emerged between gender and education, occupation, and religion. Glycemic control, with a mean HbA1c of 8.45%, remained suboptimal. Logistic regression identified gender, average family income, diabetes duration, treatment nature, comorbidities, complications, and medication adherence as glycemic control predictors. Conclusions Addressing socioeconomic and gender-specific factors is paramount in diabetes management, especially in rural areas where sociocultural influences shape health behaviors. Tailored interventions, including gender-sensitive health education, are vital for improving diabetes care and outcomes. This study provides crucial insights into gender-specific influences on glycemic control among T2DM patients in Maharashtra, advocating for personalized interventions to enhance overall diabetes management.

4.
J Family Med Prim Care ; 13(2): 713-716, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38605752

RESUMO

Background: Cosmetic products may contain ingredients whose safety is not certain with several instances of death and anaphylaxis due to service/cosmetic usage in beauty salons. With the mushrooming of beauty salons and with a large consumer base, there is a dearth in the literature to assess the awareness of the health hazards among the employees. This study aims to measure the awareness levels on health hazards and their emergency management among employees working in beauty salons in Coimbatore. Materials and Methods: A cross-sectional study using a semi-structured questionnaire, after Institutional Human Ethics Committee (IHEC) approval, was conducted*** to assess the awareness of the health hazards including emergency management among employees of beauty salons. The sample size was estimated to be 160. All the workers working in unisex beauty salons, selected by convenience sampling within 5 km radius of PSG IMS and R, were assessed based on their awareness toward cosmetics and the data were analyzed using SPSS software version 24 (IBM SPSS Statistics for Windows, Version 24.0. Armonk, NY). Results: Around 160 service providers of beauty salons participated in the study, among which 84% use several cosmetic products. Only 40% are aware of the health impacts and 21.3% are aware about the side effects which included rashes and itching associated with the products used for bleaching. Only 36.9% knew about the regulations for usage of cosmetic products and 30% knew that there is a governing body for the same. Conclusion: Awareness of health hazards and its emergency management is less among the workers; the literacy programs to improve the awareness on use of cosmetics is the need of the hour.

5.
J Alzheimers Dis Rep ; 8(1): 453-460, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38549639

RESUMO

Alzheimer's disease (AD) is an illness that affects the nervous system, leading to a loss in cognitive and logical abilities. Gene regulatory expressions, which are the complex language exhibited by DNA, serve several functionalities, including the physical and biological life cycle processes in the human body. The gene expression sequence affects the pathology experienced by an individual, its longevity, and potential for a cure. The transcription factors, from DNA to RNA conversion, and the binding process determine the gene expression, which varies for every human organ and disease. This study proposes Deep convolutional neural network model that reads the gene regulatory expression sequence through various convolutional layers encoded to detect positive spikes in transcription factors. This results in the prediction of disease conversion probability from mild cognitive impairment to AD which is the key-requisite for affected geriatric cohorts.

6.
Bol. latinoam. Caribe plantas med. aromát ; 23(2): 180-198, mar. 2024. ilus, tab, graf
Artigo em Inglês | LILACS | ID: biblio-1538281

RESUMO

India's commercial advancement and development depend heavily on agriculture. A common fruit grown in tropical settings is citrus. A professional judgment is required while analyzing an illness because different diseases have slight variati ons in their symptoms. In order to recognize and classify diseases in citrus fruits and leaves, a customized CNN - based approach that links CNN with LSTM was developed in this research. By using a CNN - based method, it is possible to automatically differenti ate from healthier fruits and leaves and those that have diseases such fruit blight, fruit greening, fruit scab, and melanoses. In terms of performance, the proposed approach achieves 96% accuracy, 98% sensitivity, 96% Recall, and an F1 - score of 92% for ci trus fruit and leave identification and classification and the proposed method was compared with KNN, SVM, and CNN and concluded that the proposed CNN - based model is more accurate and effective at identifying illnesses in citrus fruits and leaves.


El avance y desarrollo comercial de India dependen en gran medida de la agricultura. Un tipo de fruta comunmente cultivada en en tornos tropicales es el cítrico. Se requiere un juicio profesional al analizar una enfermedad porque diferentes enfermedades tienen ligeras variaciones en sus síntomas. Para reconocer y clasificar enfermedades en frutas y hojas de cítricos, se desarrolló e n esta investigación un enfoque personalizado basado en CNN que vincula CNN con LSTM. Al utilizar un método basado en CNN, es posible diferenciar automáticamente entre frutas y hojas más saludables y aquellas que tienen enfermedades como la plaga de frutas , el verdor de frutas, la sarna de frutas y las melanosis. En términos de desempeño, el enfoque propuesto alcanza una precisión del 96%, una sensibilidad del 98%, una recuperación del 96% y una puntuación F1 del 92% para la identificación y clasificación d e frutas y hojas de cítricos, y el método propuesto se comparó con KNN, SVM y CNN y se concluyó que el modelo basado en CNN propuesto es más preciso y efectivo para identificar enfermedades en frutas y hojas de cítricos.


Assuntos
Doenças das Plantas/classificação , Diagnóstico por Computador , Citrus , Redes Neurais de Computação , Folhas de Planta
7.
PLoS Biol ; 22(3): e3002522, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38483887

RESUMO

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has affected approximately 800 million people since the start of the Coronavirus Disease 2019 (COVID-19) pandemic. Because of the high rate of mutagenesis in SARS-CoV-2, it is difficult to develop a sustainable approach for prevention and treatment. The Envelope (E) protein is highly conserved among human coronaviruses. Previous studies reported that SARS-CoV-1 E deficiency reduced viral propagation, suggesting that E inhibition might be an effective therapeutic strategy for SARS-CoV-2. Here, we report inhibitory peptides against SARS-CoV-2 E protein named iPep-SARS2-E. Leveraging E-induced alterations in proton homeostasis and NFAT/AP-1 pathway in mammalian cells, we developed screening platforms to design and optimize the peptides that bind and inhibit E protein. Using Vero-E6 cells, human-induced pluripotent stem cell-derived branching lung organoid and mouse models with SARS-CoV-2, we found that iPep-SARS2-E significantly inhibits virus egress and reduces viral cytotoxicity and propagation in vitro and in vivo. Furthermore, the peptide can be customizable for E protein of other human coronaviruses such as Middle East Respiratory Syndrome Coronavirus (MERS-CoV). The results indicate that E protein can be a potential therapeutic target for human coronaviruses.


Assuntos
COVID-19 , SARS-CoV-2 , Camundongos , Animais , Chlorocebus aethiops , Humanos , Linhagem Celular , Células Vero , Peptídeos/farmacologia , Mamíferos
8.
Cell Stem Cell ; 31(2): 196-211.e6, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-38237586

RESUMO

COVID-19 patients commonly present with signs of central nervous system and/or peripheral nervous system dysfunction. Here, we show that midbrain dopamine (DA) neurons derived from human pluripotent stem cells (hPSCs) are selectively susceptible and permissive to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. SARS-CoV-2 infection of DA neurons triggers an inflammatory and cellular senescence response. High-throughput screening in hPSC-derived DA neurons identified several FDA-approved drugs that can rescue the cellular senescence phenotype by preventing SARS-CoV-2 infection. We also identified the inflammatory and cellular senescence signature and low levels of SARS-CoV-2 transcripts in human substantia nigra tissue of COVID-19 patients. Furthermore, we observed reduced numbers of neuromelanin+ and tyrosine-hydroxylase (TH)+ DA neurons and fibers in a cohort of severe COVID-19 patients. Our findings demonstrate that hPSC-derived DA neurons are susceptible to SARS-CoV-2, identify candidate neuroprotective drugs for COVID-19 patients, and suggest the need for careful, long-term monitoring of neurological problems in COVID-19 patients.


Assuntos
COVID-19 , Células-Tronco Pluripotentes , Humanos , SARS-CoV-2 , Neurônios Dopaminérgicos , Sistema Nervoso Central
9.
Curr Probl Cardiol ; 49(3): 102382, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38184131

RESUMO

Humans are becoming less active in the current age of technological advancement, which leads to poor health. Many factors, including unregulated diet, lack of exercise, environmental pollution and genetic factors are contributing to an increase in overweight. Obesity is a chronic condition that disturbs the physical health of a person, resulting in various other complications including cardiac, respiratory, and psychosocial issues. According to WHO, the current trend of obesity has shown a sharp increase in recent years. Methods ranging from as simple as regulating the diet to as complex as surgery are available. There are many approved drugs to treat the obesity majority of them works as suppressing the appetite and making the patient satisfy. Some of other agents works by insulinotropic activity. However, these agents need to be taken for longer period of time thus are associated with significant adverse drug reactions. Thus, the motive of this study is to understand obesity and the various methods available to manage it using the recent pharmacological and non-pharmacological approaches.


Assuntos
Obesidade , Sobrepeso , Humanos , Obesidade/complicações , Obesidade/epidemiologia , Obesidade/terapia , Dieta , Exercício Físico/fisiologia
10.
Antimicrob Agents Chemother ; 68(1): e0095323, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38047645

RESUMO

Molnupiravir, an oral prodrug of N-hydroxycytidine (NHC), previously demonstrated broad in vitro antiviral activity against multiple RNA viruses and has shown a high barrier to the development of resistance. Here, we present the antiviral activity of NHC against recent SARS-CoV-2 variants and the results of resistance selection studies to better understand the potential for viral resistance to NHC. NHC activity against SARS-CoV-2 variants omicron (BA.1, BA.1.1, BA.2, BA.4, BA.4.6, BA.5, BQ.1.1, XBB.1, and XBB.1.5), alpha (B.1.1.7), beta (B.1.351), gamma (P.1), delta (B.1.617.2), lambda (C.37), and mu (B.1.621) was evaluated in Vero E6 cells using cytopathic effect assays. Resistance selection studies were performed by passaging SARS-CoV-2 (WA1) in the presence of NHC or a 3C-like protease inhibitor (MRK-A) in Vero E6 cells. Supernatants from cultures exhibiting a cytopathic effect score of ≥2 were re-passaged, and IC50 values were estimated. Whole-genome deep sequencing was performed on viral RNA isolated at each passage. NHC demonstrated similar potency against all SARS-CoV-2 variants evaluated. No evidence of SARS-CoV-2 phenotypic or genotypic resistance to NHC was observed following 30 passages. A random pattern of nucleotide changes was observed in NHC cultures, consistent with the drug's mechanism of action. In contrast, resistance was readily selected in all three MRK-A control cultures with the selection of a T21I substitution in the 3C-like protease. In conclusion, molnupiravir maintains antiviral activity across all major SARS-CoV-2 variants. Furthermore, no evidence of viral resistance to NHC was observed, supporting previous reports that NHC has a high barrier to developing resistance.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Antivirais/farmacologia
11.
Nature ; 624(7992): 639-644, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37871613

RESUMO

A severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariant, BA.2.86, has emerged and spread to numerous countries worldwide, raising alarm because its spike protein contains 34 additional mutations compared with its BA.2 predecessor1. We examined its antigenicity using human sera and monoclonal antibodies (mAbs). Reassuringly, BA.2.86 was no more resistant to human sera than the currently dominant XBB.1.5 and EG.5.1, indicating that the new subvariant would not have a growth advantage in this regard. Importantly, sera from people who had XBB breakthrough infection exhibited robust neutralizing activity against all viruses tested, suggesting that upcoming XBB.1.5 monovalent vaccines could confer added protection. Although BA.2.86 showed greater resistance to mAbs to subdomain 1 (SD1) and receptor-binding domain (RBD) class 2 and 3 epitopes, it was more sensitive to mAbs to class 1 and 4/1 epitopes in the 'inner face' of the RBD that is exposed only when this domain is in the 'up' position. We also identified six new spike mutations that mediate antibody resistance, including E554K that threatens SD1 mAbs in clinical development. The BA.2.86 spike also had a remarkably high receptor affinity. The ultimate trajectory of this new SARS-CoV-2 variant will soon be revealed by continuing surveillance, but its worldwide spread is worrisome.


Assuntos
Epitopos de Linfócito B , Receptores Virais , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Humanos , Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , COVID-19/imunologia , COVID-19/virologia , Vacinas contra COVID-19/imunologia , Epitopos de Linfócito B/imunologia , Imunogenicidade da Vacina , Mutação , Receptores Virais/metabolismo , SARS-CoV-2/classificação , SARS-CoV-2/genética , SARS-CoV-2/imunologia , SARS-CoV-2/metabolismo , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/metabolismo , Soros Imunes/imunologia
12.
Immunity ; 56(10): 2442-2455.e8, 2023 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-37776849

RESUMO

SARS-CoV-2 continues to evolve, with many variants evading clinically authorized antibodies. To isolate monoclonal antibodies (mAbs) with broadly neutralizing capacities against the virus, we screened serum samples from convalescing COVID-19 patients. We isolated two mAbs, 12-16 and 12-19, which neutralized all SARS-CoV-2 variants tested, including the XBB subvariants, and prevented infection in hamsters challenged with Omicron BA.1 intranasally. Structurally, both antibodies targeted a conserved quaternary epitope located at the interface between the N-terminal domain and subdomain 1, uncovering a site of vulnerability on SARS-CoV-2 spike. These antibodies prevented viral receptor engagement by locking the receptor-binding domain (RBD) of spike in the down conformation, revealing a mechanism of virus neutralization for non-RBD antibodies. Deep mutational scanning showed that SARS-CoV-2 could mutate to escape 12-19, but such mutations are rarely found in circulating viruses. Antibodies 12-16 and 12-19 hold promise as prophylactic agents for immunocompromised persons who do not respond robustly to COVID-19 vaccines.


Assuntos
COVID-19 , Glicoproteína da Espícula de Coronavírus , Animais , Cricetinae , Humanos , Vacinas contra COVID-19 , SARS-CoV-2 , Receptores Virais , Anticorpos Monoclonais , Anticorpos Antivirais , Anticorpos Neutralizantes
13.
Heliyon ; 9(8): e18688, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37576304

RESUMO

A detailed metabolomic study was performed on various maturation stages of Murraya koenigii fruit pulps, seed, and leaf. Among the fruit pulps, stage 6 had the highest TPC (13.27 mg/g of GAE) and TFC content (6.16 mg/g RE). The extracts also showed promising free radical scavenging activity, especially in the seed (IC50DPPH 427 µg/mL). Metabolomics study revealed the identification of 133 metabolites in fruit pulps, seeds and leaves using the METLIN database. In silico PASS software analysis predicted the antimutagenic property of myricetin and bismurrayaquinone A. Pathway analysis revealed the phenylpropanoid biosynthesis pathway as one of the major pathways present in the fruit pulps. This detailed metabolic report of M. koenigii fruit maturation report brings a new insight into phytochemicals and their distribution in seed, pulps and leaves along with nutritive values and can be considered for nutritive and therapeutic purposes.

14.
RSC Adv ; 13(35): 24250-24263, 2023 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-37583660

RESUMO

A new library of peptide-heterocycle hybrids consisting of an indole-3-carboxylic acid constituent conjugated with short dipeptide motifs was designed and synthesized by using the solid phase peptide synthesis methodology. All the synthesized compounds were characterized by spectroscopic techniques. Additionally, the synthesized compounds were subjected to in vitro antimicrobial activities. Two Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) and two Gram-positive (Streptococcus pyogenes and Staphylococcus aureus) were used for the evaluation of the antibacterial activity of the targeted dipeptide derivatives. Good antibacterial activity was observed for the screened analogues by comparing their activities with that of ciprofloxacin, the standard drug. Also, two fungi (Aspergillus niger and Candida albicans) were employed for the evaluation of the antifungal activity of the synthesized compounds. When compared to the standard drug Fluconazole, it was observed that the screened analogues exhibited good antifungal activity. In continuation, all the synthesized derivatives were subjected to integrated molecular docking studies and molecular dynamics simulations to investigate binding affinities, intermolecular interaction networks, and conformational flexibilities with deoxyribonucleic acid (DNA) gyrase and lanosterol-14-alpha demethylase. The molecular docking studies revealed that indole-3-carboxylic acid conjugates exhibited encouraging binding interaction networks and binding affinity with DNA gyrase and lanosterol-14 alpha demethylase to show antibacterial and antifungal activity, respectively. Such synthesis, biological activity, molecular dynamics simulations, and molecular docking studies of short peptides with an indole conjugate unlock the door for the near future advancement of novel medicines containing peptide-heterocycle hybrids with the ability to be effective as antimicrobial agents.

15.
World J Methodol ; 13(3): 46-58, 2023 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-37456979

RESUMO

Despite the development of newer oncological treatment, the survival of patients with pancreatic cancer (PC) remains poor. Recent studies have identified exosomes as essential mediators of intercellular communications and play a vital role in tumor initiation, metastasis and chemoresistance. Thus, the utility of liquid biopsies using exosomes in PC management can be used for early detection, diagnosis, monitoring as well as drug delivery vehicles for cancer therapy. This review summarizes the function, and clinical applications of exosomes in cancers as minimally invasive liquid biomarker in diagnostic, prognostic and therapeutic roles.

16.
Nat Commun ; 14(1): 3959, 2023 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-37402814

RESUMO

Prophylactic vaccines for SARS-CoV-2 have lowered the incidence of severe COVID-19, but emergence of viral variants that are antigenically distinct from the vaccine strains are of concern and additional, broadly acting preventive approaches are desirable. Here, we report on a glycolipid termed 7DW8-5 that exploits the host innate immune system to enable rapid control of viral infections in vivo. This glycolipid binds to CD1d on antigen-presenting cells and thereby stimulates NKT cells to release a cascade of cytokines and chemokines. The intranasal administration of 7DW8-5 prior to virus exposure significantly blocked infection by three different authentic variants of SARS-CoV-2, as well as by respiratory syncytial virus and influenza virus, in mice or hamsters. We also found that this protective antiviral effect is both host-directed and mechanism-specific, requiring both the CD1d molecule and interferon-[Formula: see text]. A chemical compound like 7DW8-5 that is easy to administer and cheap to manufacture may be useful not only in slowing the spread of COVID-19 but also in responding to future pandemics long before vaccines or drugs are developed.


Assuntos
COVID-19 , Vacinas contra Influenza , Influenza Humana , Camundongos , Animais , Humanos , SARS-CoV-2 , COVID-19/prevenção & controle , Vacinas contra COVID-19
17.
Sci Transl Med ; 15(697): eadf4549, 2023 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-37224226

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has been responsible for a global pandemic. Monoclonal antibodies (mAbs) have been used as antiviral therapeutics; however, these therapeutics have been limited in efficacy by viral sequence variability in emerging variants of concern (VOCs) and in deployment by the need for high doses. In this study, we leveraged the multi-specific, multi-affinity antibody (Multabody, MB) platform, derived from the human apoferritin protomer, to enable the multimerization of antibody fragments. MBs were shown to be highly potent, neutralizing SARS-CoV-2 at lower concentrations than their corresponding mAb counterparts. In mice infected with SARS-CoV-2, a tri-specific MB targeting three regions within the SARS-CoV-2 receptor binding domain was protective at a 30-fold lower dose than a cocktail of the corresponding mAbs. Furthermore, we showed in vitro that mono-specific MBs potently neutralize SARS-CoV-2 VOCs by leveraging augmented avidity, even when corresponding mAbs lose their ability to neutralize potently, and that tri-specific MBs expanded the neutralization breadth beyond SARS-CoV-2 to other sarbecoviruses. Our work demonstrates how avidity and multi-specificity combined can be leveraged to confer protection and resilience against viral diversity that exceeds that of traditional monoclonal antibody therapies.


Assuntos
COVID-19 , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave , Humanos , Animais , Camundongos , SARS-CoV-2 , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Antivirais
18.
bioRxiv ; 2023 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-37090592

RESUMO

SARS-CoV-2 continues to evolve and evade most existing neutralizing antibodies, including all clinically authorized antibodies. We have isolated and characterized two human monoclonal antibodies, 12-16 and 12-19, which exhibited neutralizing activities against all SARS-CoV-2 variants tested, including BQ.1.1 and XBB.1.5. They also blocked infection in hamsters challenged with Omicron BA.1 intranasally. Structural analyses revealed both antibodies targeted a conserved quaternary epitope located at the interface between the N-terminal domain and subdomain 1, revealing a previously unrecognized site of vulnerability on SARS-CoV-2 spike. These antibodies prevent viral receptor engagement by locking the receptor-binding domain of spike in the down conformation, revealing a novel mechanism of virus neutralization for non-RBD antibodies. Deep mutational scanning showed that SARS-CoV-2 could mutate to escape 12-19, but the responsible mutations are rarely found in circulating viruses. Antibodies 12-16 and 12-19 hold promise as prophylactic agents for immunocompromised persons who do not respond robustly to COVID-19 vaccines.

19.
Cureus ; 15(3): e35800, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37033515

RESUMO

Background Primary health centres are in charge of effectively implementing the COVID-19 vaccination program in rural areas. So, the study was planned to seek insight into the challenges faced by health personnel in the effective implementation of the COVID-19 vaccination program. Methodology The study was conducted in a rural area of Akola district which lies in the western parts of Maharashtra State and belongs to the Vidarbha region and is said to be one of the progressive districts in the region. A qualitative study was planned to understand the barriers and facilitators of the COVID-19 vaccine implementation program at rural and tribal areas. The study participants were medical officers from rural and tribal areas who actively planned and implemented COVID-19 vaccination at the primary health centre. A total of 30 medical officers were interviewed. Interview questions were focussed on the planning of COVID-19 vaccination in their area. Other questions were the problem faced during the implementation of the COVID-19 vaccination program and how it has been tackled. Results The factors identified were grouped into three groups: Health system factors, Human resource factors and Community level factors. Health system factors like shortage of vaccines and syringes, tablet paracetamol, online digital method of vaccination registration, overcrowding at the initial stage, and inadequate infrastructure were barriers to vaccination. Fear about vaccine adverse events, even in healthcare workers (HCWs), and overburdened healthcare workers were also factors affecting vaccination. At the community level, high resistance initially and misconception about the vaccine, and also the fear about post-vaccination side effects have an impact on the COVID-19 vaccination program in rural and tribal areas. Conclusion The successful vaccination rate among the population needs community leadership and a community-centred approach when conducting outreach and strengthening primary health care in terms of infrastructure, manpower, and capacity building of healthcare staff.

20.
iScience ; 26(4): 106345, 2023 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-36925721

RESUMO

A better understanding of the durability and breadth of serum-neutralizing antibody responses against multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants elicited by COVID-19 vaccines is crucial in addressing the current pandemic. In this study, we quantified the decay of serum neutralization antibodies (nAbs) after second and third doses of the original COVID-19 mRNA vaccine. Using an authentic virus-neutralization assay, we found that decay half-lives of WA1- and Delta-nAbs were both ∼60 days after second and third vaccine dose. Unexpectedly, the durability of serum antibodies that neutralize three different Omicron subvariants (BA.1.1, BA.5, BA.2.12.1) was substantially better, with half-lives of ≥6 months. A booster dose of the original COVID-19 vaccine was also found to broaden antibody responses against SARS-CoV and four other sarbecoviruses, in addition to multiple SARS-CoV-2 strains. These findings suggest that repeated vaccinations with the COVID-19 vaccine may confer a degree of protection against future spillover of sarbecoviruses from animal reservoirs.

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