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Effective Reduction of SARS-CoV-2 RNA Levels Using a Tailor-Made Oligonucleotide-Based RNA Inhibitor
Veronika Nemethova Petra Mazancova Michal Selc Kristina Jakic Lucia Uhelska Boglarka Nemethova Alexandra Poturnayova Lubos Drgona Andrea Babelova Filip Razga 《Viruses》2022,14(4)
In only two years, the coronavirus disease 2019 (COVID-19) pandemic has had a devastating effect on public health all over the world and caused irreparable economic damage across all countries. Due to the limited therapeutic management of COVID-19 and the lack of tailor-made antiviral agents, finding new methods to combat this viral illness is now a priority. Herein, we report on a specific oligonucleotide-based RNA inhibitor targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It displayed remarkable spontaneous cellular uptake, >94% efficiency in reducing RNA-dependent RNA polymerase (RdRp) RNA levels in transfected lung cell lines, and >98% efficiency in reducing SARS-CoV-2 RNA levels in samples from patients hospitalized with COVID-19 following a single application. 相似文献
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Erol C. Vatansever Kai S. Yang Aleksandra K. Drelich Kaci C. Kratch Chia-Chuan Cho Kempaiah Rayavara Kempaiah Jason C. Hsu Drake M. Mellott Shiqing Xu Chien-Te K. Tseng Wenshe Ray Liu 《Proceedings of the National Academy of Sciences of the United States of America》2021,118(10)
Guided by a computational docking analysis, about 30 Food and Drug Administration/European Medicines Agency (FDA/EMA)-approved small-molecule medicines were characterized on their inhibition of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro). Of these small molecules tested, six displayed a concentration that inhibits response by 50% (IC50) value below 100 μM in inhibiting Mpro, and, importantly, three, that is, pimozide, ebastine, and bepridil, are basic molecules that potentiate dual functions by both raising endosomal pH to interfere with SARS-CoV-2 entry into the human cell host and inhibiting Mpro in infected cells. A live virus-based modified microneutralization assay revealed that bepridil possesses significant anti−SARS-CoV-2 activity in both Vero E6 and A459/ACE2 cells in a dose-dependent manner with low micromolar effective concentration, 50% (EC50) values. Therefore, the current study urges serious considerations of using bepridil in COVID-19 clinical tests.The current worldwide impact of the COVID-19 pandemic has been so profound that it is often compared to that of the 1918 influenza pandemic (1, 2). As of February 4, 2021, the total global COVID-19 cases had surpassed 100 million, among which more than 2 million had succumbed to death (3). Important political figures who have been diagnosed COVID-19 positive include the US president Donald Trump and the UK prime minister Boris Johnson. A modeling study has predicted that this pandemic will continue to affect everyday life, and the circumstances may require societies to follow social distancing until 2022 (4). Finding timely treatment options is of tremendous importance to alleviate catastrophic damages of COVID-19. However, the short time window that is required to contain the disease is extremely challenging for a conventional drug discovery process that requires typically many years to finalize a drug and therefore might not achieve its goal before the pandemic ceases. In January 2020, we did a comparative biochemical analysis between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that has caused COVID-19, and SARS-CoV-1 that led to an epidemic in China in 2003, and proposed that remdesivir was a viable choice for the treatment of COVID-19 (5). We were excited to see that remdesivir was finally approved for emergency use in the United States and for use in Japan for people with severe symptoms. With only one medicine in stock that provides very limited benefits to COVID-19 patients (6), the virus may easily evade it, leaving us once again with no medicine to use. Given the rapid spread and the high fatality rate of COVID-19, finding alternative medicines is imperative. Drug repurposing stands out as an attractive option in the current situation. If an approved drug can be identified to treat COVID-19, it can quickly proceed to clinical trials and be manufactured at a large scale using its existing good manufacturing practice (GMP) lines. Previously, encouraging results were obtained from repurposing small-molecule medicines, including teicoplanin, ivermectin, itraconazole, and nitazoxanide (7–10). These antimicrobial agents showed antiviral activity against Ebola, Chikungunya, enterovirus, and influenza viruses, respectively (11). However, a common drawback of a repurposed drug is its low efficacy level. One way to circumvent this problem is to combine multiple existing medicines to accrue a synergistic effect. To be able to discover such combinations, breaking down the druggable targets of SARS-CoV-2 to identify drugs that do not cross-act on each other’s targets is a promising strategy. For example, a recent study showed that triple combination of interferon β-1b, lopinavir−ritonavir, and ribavirin was safe and superior to lopinavir−ritonavir alone for treating COVID-19 patients (12).In our January paper (5), we recommended four SARS-CoV-2 essential proteins, including Spike, RNA-dependent RNA polymerase, the main protease (Mpro), and papain-like protease, as drug targets for the development of anti−COVID-19 therapeutics. Among these four proteins, Mpro that was previously called 3C-like protease provides the most facile opportunity for drug repurposing, owing to the ease of its biochemical assays. Mpro is a cysteine protease that processes itself and then cleaves a number of nonstructural viral proteins from two very large polypeptide translates that are made from the viral genomic RNA in the human cell host (13). Its relatively large active site pocket and a highly nucleophilic, catalytic cysteine residue make it likely to be inhibited by a host of existing and investigational drugs. Previous work has disclosed some existing drugs that inhibit Mpro (14). However, complete characterization of existing drugs on the inhibition of Mpro is not yet available. Since the release of the first Mpro crystal structure, many computational studies have been carried out to screen existing drugs in their inhibition of Mpro, and many potent leads have been proposed (15–18). However, most of these lead drugs are yet to be confirmed experimentally. To investigate whether some existing drugs can potently inhibit Mpro, we have docked a group of selected Food and Drug Administration/European Medicines Agency (FDA/EMA)-approved small-molecule medicines to the active site of Mpro and selected about 30 hit drugs to characterize their inhibition on Mpro experimentally. Our results revealed that a number of FDA/EMA-approved small-molecule medicines have high potency in inhibiting Mpro, and bepridil inhibits cytopathogenic effect (CPE) induced by the SARS-CoV-2 virus in Vero E6 and A549/ACE2 cells with low micromolar effective concentration, 50% (EC50) values. Therefore, the current study encourages further preclinical testing of bepridil in animal models, paving the way to its clinical use against COVID-19. 相似文献
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During the last two years following the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, development of potent antiviral drugs and vaccines has been a global health priority. In this context, the understanding of virus pathophysiology, the identification of associated therapeutic targets, and the screening of potential effective compounds have been indispensable advancements. It was therefore of primary importance to develop experimental models that recapitulate the aspects of the human disease in the best way possible. This article reviews the information concerning available SARS-CoV-2 preclinical models during that time, including cell-based approaches and animal models. We discuss their evolution, their advantages, and drawbacks, as well as their relevance to drug effectiveness evaluation. 相似文献
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Carolina Q. Sacramento Natalia Fintelman-Rodrigues Suelen S. G. Dias Jairo R. Temerozo Aline de Paula D. Da Silva Carine S. da Silva Camilla Blanco Andr C. Ferreira Mayara Mattos Vinicius C. Soares Filipe Pereira-Dutra Milene Dias Miranda Debora F. Barreto-Vieira Marcos Alexandre N. da Silva Suzana S. Santos Mateo Torres Otvio Augusto Chaves Rajith K. R. Rajoli Alberto Paccanaro Andrew Owen Dumith Chequer Bou-Habib Patrícia T. Bozza Thiago Moreno L. Souza 《Viruses》2022,14(2)
Despite the development of specific therapies against severe acute respiratory coronavirus 2 (SARS-CoV-2), the continuous investigation of the mechanism of action of clinically approved drugs could provide new information on the druggable steps of virus–host interaction. For example, chloroquine (CQ)/hydroxychloroquine (HCQ) lacks in vitro activity against SARS-CoV-2 in TMPRSS2-expressing cells, such as human pneumocyte cell line Calu-3, and likewise, failed to show clinical benefit in the Solidarity and Recovery clinical trials. Another antimalarial drug, mefloquine, which is not a 4-aminoquinoline like CQ/HCQ, has emerged as a potential anti-SARS-CoV-2 antiviral in vitro and has also been previously repurposed for respiratory diseases. Here, we investigated the anti-SARS-CoV-2 mechanism of action of mefloquine in cells relevant for the physiopathology of COVID-19, such as Calu-3 cells (that recapitulate type II pneumocytes) and monocytes. Molecular pathways modulated by mefloquine were assessed by differential expression analysis, and confirmed by biological assays. A PBPK model was developed to assess mefloquine’s optimal doses for achieving therapeutic concentrations. Mefloquine inhibited SARS-CoV-2 replication in Calu-3, with an EC50 of 1.2 µM and EC90 of 5.3 µM. It reduced SARS-CoV-2 RNA levels in monocytes and prevented virus-induced enhancement of IL-6 and TNF-α. Mefloquine reduced SARS-CoV-2 entry and synergized with Remdesivir. Mefloquine’s pharmacological parameters are consistent with its plasma exposure in humans and its tissue-to-plasma predicted coefficient points suggesting that mefloquine may accumulate in the lungs. Altogether, our data indicate that mefloquine’s chemical structure could represent an orally available host-acting agent to inhibit virus entry. 相似文献
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The SARS-CoV-2 pandemic has urged the development of protective vaccines and the search for specific antiviral drugs. The modern molecular biology tools provides alternative methods, such as CRISPR-Cas and RNA interference, that can be adapted as antiviral approaches, and contribute to this search. The unique CRISPR-Cas13d system, with the small crRNA guide molecule, mediates a sequence-specific attack on RNA, and can be developed as an anti-coronavirus strategy. We analyzed the SARS-CoV-2 genome to localize the hypothetically best crRNA-annealing sites of 23 nucleotides based on our extensive expertise with sequence-specific antiviral strategies. We considered target sites of which the sequence is well-conserved among SARS-CoV-2 isolates. As we should prepare for a potential future outbreak of related viruses, we screened for targets that are conserved between SARS-CoV-2 and SARS-CoV. To further broaden the search, we screened for targets that are conserved between SARS-CoV-2 and the more distantly related MERS-CoV, as well as the four other human coronaviruses (OC43, 229E, NL63, HKU1). Finally, we performed a search for pan-corona target sequences that are conserved among all these coronaviruses, including the new Omicron variant, that are able to replicate in humans. This survey may contribute to the design of effective, safe, and escape-proof antiviral strategies to prepare for future pandemics. 相似文献
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Milan Dejmek Eva Konkoov Ludk Eyer Petra Strakov Pavel Svoboda Michal la Kateina Krej
ov Daniel Rek Evzen Boura Radim Nencka 《Viruses》2021,13(8)
SARS-CoV-2 has caused an extensive pandemic of COVID-19 all around the world. Key viral enzymes are suitable molecular targets for the development of new antivirals against SARS-CoV-2 which could represent potential treatments of the corresponding disease. With respect to its essential role in the replication of viral RNA, RNA-dependent RNA polymerase (RdRp) is one of the prime targets. HeE1-2Tyr and related derivatives were originally discovered as inhibitors of the RdRp of flaviviruses. Here, we present that these pyridobenzothiazole derivatives also significantly inhibit SARS-CoV-2 RdRp, as demonstrated using both polymerase- and cell-based antiviral assays. 相似文献
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Jingwei Wang Anyu Bao Jian Gu Xiaoyun He Zegang Wu Bin Qiao Zhen Chen Liang Xiong Yan Zhang Hongyun Zheng Feng Li Zhijun Zhao Siqing Mei Yongqing Tong 《Medicine》2021,100(20)
The outbreak and widely spread of coronavirus disease 2019 (COVID-19) has become a global public health concern. COVID-19 has caused an unprecedented and profound impact on the whole world, and the prevention and control of COVID-19 is a global public health challenge remains to be solved. The retrospective analysis of the large scale tests of SARS-CoV-2 RNA may indicate some important information of this pandemic. We selected 12400 SARS-CoV-2 tests detected in Wuhan in the first semester of 2020 and made a systematic analysis of them, in order to find some beneficial clue for the consistent prevention and control of COVID-19.SARS-CoV-2 RNA was detected in suspected COVID-19 patients with real-time fluorescence quantitative PCR (RT-qPCR). The patients’ features including gender, age, type of specimen, source of patients, and the dynamic changes of the clinical symptoms were recorded and statistically analyzed. Quantitative and qualitive statistical analysis were carried out after laboratory detection.The positive rate of SARS-CoV-2 was 33.02% in 12,400 suspected patients’ specimens in Wuhan at the first months of COVID-19 epidemics. SARS-CoV-2 RT-qPCR test of nasopharyngeal swabs might produce 4.79% (594/12400) presumptive results. The positive rate of SARS-CoV-2 RNA was significantly different between gender, age, type of specimen, source of patients, respectively (P < .05). The median window period from the occurrence of clinical symptom or close contact with COVID-19 patient to the first detection of positive PCR was 2 days (interquartile range, 1–4 days). The median interval time from the first SARS-CoV-2 positive to the turning negative was 14 days (interquartile range, 8–19.25 days).This study reveals the comprehensive characteristics of the SARS-CoV-2 RNA detection from multiple perspectives, and it provides important clues and may also supply useful suggestions for future work of the prevention and treatment of COVID-19. 相似文献
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Carmen Mirabelli Jesse W. Wotring Charles J. Zhang Sean M. McCarty Reid Fursmidt Carla D. Pretto Yuanyuan Qiao Yuping Zhang Tristan Frum Namrata S. Kadambi Anya T. Amin Teresa R. OMeara Jason R. Spence Jessie Huang Konstantinos D. Alysandratos Darrell N. Kotton Samuel K. Handelman Christiane E. Wobus Kevin J. Weatherwax George A. Mashour Matthew J. OMeara Arul M. Chinnaiyan Jonathan Z. Sexton 《Proceedings of the National Academy of Sciences of the United States of America》2021,118(36)
The global spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the associated disease COVID-19, requires therapeutic interventions that can be rapidly identified and translated to clinical care. Traditional drug discovery methods have a >90% failure rate and can take 10 to 15 y from target identification to clinical use. In contrast, drug repurposing can significantly accelerate translation. We developed a quantitative high-throughput screen to identify efficacious agents against SARS-CoV-2. From a library of 1,425 US Food and Drug Administration (FDA)-approved compounds and clinical candidates, we identified 17 hits that inhibited SARS-CoV-2 infection and analyzed their antiviral activity across multiple cell lines, including lymph node carcinoma of the prostate (LNCaP) cells and a physiologically relevant model of alveolar epithelial type 2 cells (iAEC2s). Additionally, we found that inhibitors of the Ras/Raf/MEK/ERK signaling pathway exacerbate SARS-CoV-2 infection in vitro. Notably, we discovered that lactoferrin, a glycoprotein found in secretory fluids including mammalian milk, inhibits SARS-CoV-2 infection in the nanomolar range in all cell models with multiple modes of action, including blockage of virus attachment to cellular heparan sulfate and enhancement of interferon responses. Given its safety profile, lactoferrin is a readily translatable therapeutic option for the management of COVID-19.Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped, positive-sense, single-stranded RNA betacoronavirus that emerged in Wuhan, China in November 2019 and rapidly developed into a global pandemic. The associated disease, COVID-19, manifests with an array of symptoms, ranging from flu-like illness and gastrointestinal distress (1, 2) to acute respiratory distress syndrome, heart arrhythmias, strokes, and death (3, 4). Recently, the US Food and Drug Administration (FDA) issued emergency approval of remdesivir, a nucleoside inhibitor prodrug developed for Ebola virus treatment (5). Although large-scale vaccination is ongoing worldwide, the need for safe, readily available antivirals is still a clinical priority. An antiviral compound that curbs infection and reduces COVID-19 symptoms would be highly useful to control local outbreaks or for home-based management, to protect immunocompromised patients for whom vaccination strategies are not suitable, and to slow the spread of variants of concern that could escape vaccine neutralization.Repurposing of FDA-approved drugs is a promising strategy for identifying rapidly deployable treatments for COVID-19. Benefits of repurposing include known safety profiles, robust supply chains, and a short time frame necessary for development (6). Additionally, approved drugs can serve as chemical probes to understand the biology of viral infection and inform on the molecular targets/pathways that influence SARS-CoV-2 infection. To date, several drug repurposing screening efforts have been reported in various cell systems including nonhuman primate VeroE6 (7), Huh7.5 (8), and Caco-2 cells (9) with a significant overlap in reported drugs but with wide-ranging potencies. Here, we developed a pipeline for quantitative high-throughput image-based screening of SARS-CoV-2 infection that led to the identification of several FDA-approved drugs and clinical candidates with previously unreported in vitro antiviral activity. We also determined that inhibitors of the Ras/Raf/MEK/ERK signaling pathway exhibited proviral activity in Huh7 cells. Mechanism of action studies of lactoferrin, the most promising hit, identified that it inhibits viral attachment, enhances antiviral host cell responses, and potentiates the effects of remdesivir. 相似文献
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2019年12月底,湖北省武汉市暴发了由新型冠状病毒(SARS-CoV-2)引起的肺炎疫情.迄今为止,该病毒引起的疫情仍在全球流行,累计感染人数超1.8亿.随着SARS-CoV-2在人群间的不断传播,其基因组不断发生变异,从SARS-CoV-2首次出现S蛋白D614G突变到被世界卫生组织列为关切的Alpha、Beta、... 相似文献
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《Viruses》2021,13(8)
The SARS-CoV-2 pandemic, which came to Russia in March 2020, is accompanied by morbidity level changes and can be tracked using serological monitoring of a representative population sample from Federal Districts (FDs) and individual regions. In a longitudinal cohort study conducted in 26 model regions of Russia, distributed across all FDs, we investigated the distribution and cumulative proportions of individuals with antibodies (Abs) to the SARS-CoV-2 nucleocapsid antigen (Ag), in the period from June to December 2020, using a three-phase monitoring process. In addition, during the formation of the cohort of volunteers, the number of seropositive convalescents, persons who had contact with patients or COVID-19 convalescents, and the prevalence of asymptomatic forms of infection among seropositive volunteers were determined. According to a uniform methodology, 3 mL of blood was taken from the examined individuals, and plasma was separated, from which the presence of Abs to nucleocapsid Ag was determined on a Thermo Scientific Multiascan FC device using the “ELISA anti-SARS-CoV-2 IgG” reagent set (prod. Scientific Center for Applied Microbiology and Biotechnology), in accordance with the developer’s instructions. Volunteers (74,158) were surveyed and divided into seven age groups (1–17, 18–29, 30–39, 40–49, 59–59, 60–69, and 70+ years old), among whom 14,275 were identified as having antibodies to SARS-CoV-2. The average percent seropositive in Russia was 17.8% (IQR: 8.8–23.2). The largest proportion was found among children under 17 years old (21.6% (IQR: 13.1–31.7). In the remaining groups, seroprevalence ranged from 15.6% (IQR: 8–21.1) to 18.0% (IQR: 13.4–22.6). During monitoring, three (immune) response groups were found: (A) groups with a continuous increase in the proportion of seropositive; (B) those with a slow rate of increase in seroprevalence; and (C) those with a two-phase curve, wherein the initial increase was replaced by a decrease in the percentage of seropositive individuals. A significant correlation was revealed between the number of COVID-19 convalescents and contact persons, and between the number of contacts and healthy seropositive volunteers. Among the seropositive volunteers, more than 93.6% (IQR: 87.1–94.9) were asymptomatic. The results show that the COVID-19 pandemic is accompanied by an increase in seroprevalence, which may be important for the formation of herd immunity. 相似文献
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Su Datt Lam Paul Ashford Sandra Díaz-Snchez Margarita Villar Christian Gortzar Jos de la Fuente Christine Orengo 《Viruses》2021,13(4)
Coronavirus-like organisms have been previously identified in Arthropod ectoparasites (such as ticks and unfed cat flea). Yet, the question regarding the possible role of these arthropods as SARS-CoV-2 passive/biological transmission vectors is still poorly explored. In this study, we performed in silico structural and binding energy calculations to assess the risks associated with possible ectoparasite transmission. We found sufficient similarity between ectoparasite ACE and human ACE2 protein sequences to build good quality 3D-models of the SARS-CoV-2 Spike:ACE complex to assess the impacts of ectoparasite mutations on complex stability. For several species (e.g., water flea, deer tick, body louse), our analyses showed no significant destabilisation of the SARS-CoV-2 Spike:ACE complex, suggesting these species would bind the viral Spike protein. Our structural analyses also provide structural rationale for interactions between the viral Spike and the ectoparasite ACE proteins. Although we do not have experimental evidence of infection in these ectoparasites, the predicted stability of the complex suggests this is possible, raising concerns of a possible role in passive transmission of the virus to their human hosts. 相似文献
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At present, the RT-PCR test remains the gold standard for early diagnosis of SARS-CoV-2. Nevertheless, there is growing evidence demonstrating that this technique may generate false-negative results. Here, we aimed to compare the new mass spectrometry-based assay MassARRAY® SARS-CoV-2 Panel with the RT-PCR diagnostic test approved for clinical use. The study group consisted of 168 suspected patients with symptoms of a respiratory infection. After simultaneous analysis by RT-PCR and mass spectrometry methods, we obtained discordant results for 17 samples (10.12%). Within fifteen samples officially reported as presumptive positive, 13 were positive according to the MS-based assay. Moreover, four samples reported by the officially approved RT-PCR as negative were positive in at least one MS assay. We have successfully demonstrated superior sensitivity of the MS-based assay in SARS-CoV-2 detection, showing that MALDI-TOF MS seems to be ideal for the detection as well as discrimination of mutations within the viral genome. 相似文献
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为抗击2019年冠状病毒病(COVID-19)全球大流行,世界各地投入了大量资源开展基因组测序,目前已有超过55 000个SARS-CoV-2毒株序列汇集到GISAID网站。由于SARS-CoV-2病毒基因组较大、编码相对复杂,给基因组流行病学分析带来了挑战。本文总结了目前SARS-CoV-2病毒基因组流行病学研究进展,以便专业人员及时了解SARS-CoV-2病毒特征及传播趋势,充分利用基因组流行病学平台资源和工具,推动疫苗研制和治疗药物开发,促进这场全球大流行疫情的防控。 相似文献
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Stuart Dowall Francisco J. Salguero Nathan Wiblin Susan Fotheringham Graham Hatch Simon Parks Kathryn Gowan Debbie Harris Oliver Carnell Rachel Fell Robert Watson Victoria Graham Karen Gooch Yper Hall Simon Mizen Roger Hewson 《Viruses》2021,13(11)
The global pandemic of coronavirus disease (COVID-19) caused by infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to an international thrust to study pathogenesis and evaluate interventions. Experimental infection of hamsters and the resulting respiratory disease is one of the preferred animal models since clinical signs of disease and virus shedding are similar to more severe cases of human COVID-19. The main route of challenge has been direct inoculation of the virus via the intranasal route. To resemble the natural infection, we designed a bespoke natural transmission cage system to assess whether recipient animals housed in physically separate adjacent cages could become infected from a challenged donor animal in a central cage, with equal airflow across the two side cages. To optimise viral shedding in the donor animals, a low and moderate challenge dose were compared after direct intranasal challenge, but similar viral shedding responses were observed and no discernible difference in kinetics. The results from our natural transmission set-up demonstrate that most recipient hamsters are infected within the system developed, with variation in the kinetics and levels of disease between individual animals. Common clinical outputs used for the assessment in directly-challenged hamsters, such as weight loss, are less obvious in hamsters who become infected from naturally acquiring the infection. The results demonstrate the utility of a natural transmission model for further work on assessing the differences between virus strains and evaluating interventions using a challenge system which more closely resembles human infection. 相似文献
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Xingyun Wang Nino Rcheulishvili Jie Cai Cong Liu Fengfei Xie Xing Hu Nuo Yang Mengqi Hou Dimitri Papukashvili Yunjiao He Peng George Wang 《Viruses》2022,14(5)
Despite the existence of various types of vaccines and the involvement of the world’s leading pharmaceutical companies, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains the most challenging health threat in this century. Along with the increased transmissibility, new strains continue to emerge leading to the need for more vaccines that would elicit protectiveness and safety against the new strains of the virus. Nucleic acid vaccines seem to be the most effective approach in case of a sudden outbreak of infection or the emergence of a new strain as it requires less time than any conventional vaccine development. Hence, in the current study, a DNA vaccine encoding the trimeric prefusion-stabilized ectodomain (S1+S2) of SARS-CoV-2 S-protein was designed by introducing six additional prolines mutation, termed HexaPro. The three-dose regimen of designed DNA vaccine immunization in mice demonstrated the generation of protective antibodies. 相似文献
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Tendesayi Kufa Waasila Jassat Cheryl Cohen Stefano Tempia Maureen Masha Nicole Wolter Sibongile Walaza Anne von Gottburg Nelesh P. Govender Gillian Hunt Andronica Moipone Shonhiwa Joy Ebonwu Genevie Ntshoe Wellington Maruma Poncho Bapela Nomathamsanqa Ndhlovu Hlengani Mathema Motshabi Modise Liliwe Shuping Pinky N. Manana David Moore Ziyaad Dangor Charl Verwey Shabir A. Madhi Haroon Saloojee Heather J. Zar Lucille Blumberg 《Influenza and other respiratory viruses》2022,16(1):34-47