mRNA Vaccines: Possible Tools to Combat SARS-CoV-2

正Coronaviruses are large, enveloped, positive-strand RNA viruses. Several coronaviruses are pathogenic in humans,including severe acute respiratory syndrome coronavirus(SARS-CoV), Middle East respiratory syndrome coronavirus(MERS-CoV) and this novel virus, SARS-CoV-2,     

Recovery of Deleted Deep Sequencing Data Sheds More Light on the Early Wuhan SARS-CoV-2 Epidemic

The origin and early spread of SARS-CoV-2 remains shrouded in mystery. Here, I identify a data set containing SARS-CoV-2 sequences from early in the Wuhan epidemic that has been deleted from the NIH’s Sequence Read Archive. I recover the deleted files from the Google Cloud and reconstruct partial sequences of 13 early epidemic viruses. Phylogenetic analysis of these sequences in the context of carefully annotated existing data further supports the idea that the Huanan Seafood Market sequences are not fully representative of the viruses in Wuhan early in the epidemic. Instead, the progenitor of currently known SARS-CoV-2 sequences likely contained three mutations relative to the market viruses that made it more similar to SARS-CoV-2’s bat coronavirus relatives.     

Experimental Models for SARS-CoV-2 Infection

Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is a novel virus that causes coronavirus disease 2019 (COVID-19). To understand the identity, functional characteristics and therapeutic targets of the virus and the diseases, appropriate infection models that recapitulate the in vivo pathophysiology of the viral infection are necessary. This article reviews the various infection models, including Vero cells, human cell lines, organoids, and animal models, and discusses their advantages and disadvantages. This knowledge will be helpful for establishing an efficient system for defense against emerging infectious diseases.     

A lipidomic view of SARS-CoV-2

The global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which started in late 2019, has caused huge social and economic losses. A growing number of investigators are focusing on understanding the interaction of SARS-CoV-2 with host cellular processes to find therapeutic approaches. New data suggest that lipid metabolism may play a significant role in regulating the response of immune cells like macrophages to viral infection, thereby affecting the outcome of the disease. Therefore, understanding the role of lipid metabolism could help develop new therapeutic approaches to mitigate the social and economic cost of coronavirus disease 2019 (COVID-19).     

Protective Effect of Melatonin Administration against SARS-CoV-2 Infection: A Systematic Review

Introduction: according to the World Health Organization (WHO), COVID-19 is an infectious disease caused by the SARS-CoV-2 virus, responsible for an increasing number of cases and deaths. From a preventive and therapeutic point of view, there are two concerns that affect institutions and healthcare professionals: global immunization (which is still far from being achieved) and the availability of drugs capable of preventing its consequences in the infected patient. In this sense, the role that melatonin can play is has been assessed in the recent literature. Justification and Objectives: the serious health, social and economic consequences of COVID-19 have forced an urgent search for preventive methods, such as vaccines, among others, and therapeutic methods that could be alternatives to the drugs currently used. In this sense, it must be accepted that one of the most recommended has been the administration of melatonin. The present study proposes to carry out a systematic review of its possible role in the treatment and/or prevention of COVID-19. Material and methods: a systematic review of the literature related to the prevention of COVID-19 through the administration of melatonin was carried out, following the sequence proposed by the Prisma Declaration regarding the identification and selection of documents, using the specialized health databases Trip Medical Database, Cochrane Library, PubMed, Medline Plus, BVS, Cuiden and generic databases such as Dialnet, Web of Science and Google Scholar for their retrieval. Appropriate inclusion and exclusion criteria are described for the articles assessed. The main limitation of the study has been the scarcity of works and the lack of defining a specific protocol in terms of dosage and administration schedule. Results: once the selection process was completed, and after an in-depth critical analysis, 197 papers were selected, and 40 of them were finally used. The most relevant results were: (1) melatonin prevents SARS-CoV-2 infection, (2) although much remains to be clarified, at high doses, it seems to have a coadjuvant therapeutic effect in the treatment of SARS-CoV-2 infection and (3) melatonin is effective against SARS-CoV-2 infection. Discussion: until group immunization is achieved in the population, it seems clear that we must continue to treat patients with SARS-CoV-2 infection, and, in the absence of a specific and effective antiviral therapy, it is advisable to continue researching and providing drugs that demonstrate validity based on the scientific evidence. In this regard, we believe that the available studies recommend the administration of melatonin for its anti-inflammatory, antioxidant, immunomodulatory, sleep-inducing, CD147, Mpro, p65 and MMP9 protein suppressing, nephrotoxicity-reducing and highly effective and safe effects. Conclusions: (1) melatonin has anti-inflammatory, antioxidant, immunomodulatory, and Mpro and MMP9 protein-inhibitory activity. (2) It has been shown to have a wide margin of safety. (3) The contributions reviewed make it an effective therapeutic alternative in the treatment of SARS-CoV-2 infection. (4) Further clinical trials are recommended to clearly define the administration protocol.     

Assessment of global asymptomatic SARS-CoV-2 infection and management practices from China

With ongoing research, it was found that asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was widespread in coronavirus disease 2019 (COVID-19) populations. Studies have confirmed asymptomatic patients with COVID-19 have potential infectivity, and most of the transmission occurred before symptoms appear. Asymptomatic infection rates varied widely in different countries and regions. Identifying the asymptomatic infected persons and cutting off the infection source is an effective way to prevent the spread of this disease. However, asymptomatic patients have hidden clinical symptoms, and screening based only on the clinical symptoms of COVID-19 can easily lead to a missed diagnosis. Therefore, determining asymptomatic infection patients by SARS-CoV-2 nucleic acid testing is the gold standard. A series of prevention and control measures adopted by the Chinese government, especially the “Four Early” policy, have achieved outstanding achievements, which are worth learning from by other countries.     

新型冠状病毒序列变异时空分析系统的设计与实现

新型冠状病毒肺炎目前已进入全球大流行状态,多个国家出现疫情爆发。美国疾病管制局期刊《新兴传染病》发表的关于新型冠状病毒的最新研究结论显示,新型冠状病毒基本传染数R0的中位数高达5.7,这意味着在未来较长时间内新型冠状病毒可能会在人群中持续传播并发生变异。在这一背景下,如何监视病毒的变异,对于冠状病毒的研究和药物研发具有重要意义。本文基于来自GISAID的病毒基因组序列数据,设计和实现了新型冠状病毒变异时空分析系统。该系统可对来自不同国家和地区的新型冠状病毒序列数进行统计,对病毒序列在不同时间、不同空间内的变异情况进行分析和可视化,同时还支持不同序列之间的差异比对。该系统可为新型冠状病毒肺炎的研究和政府的疾病控制机构的决策提供支持。     

新型冠状病毒亚单位疫苗研究进展及现状*

自新型冠状病毒肺炎在2019年年末暴发以来,如何高效防控疫情一直是紧急的全球公共安全事件。疫苗是有效阻止病毒感染人体、保护高危人群免于疾病快速进展以及遏制疫情进一步扩大的手段之一,其中亚单位疫苗的主要成分为特定的病毒抗原蛋白或多肽,通过加入疫苗佐剂提高抗原的免疫原性。由于机体仅针对重组蛋白表面的特定抗原表位进行识别并产生抗体,因此亚单位疫苗具有较高的保护能力和安全性。通过对目前已上市及处于临床阶段的各类新型冠状病毒亚单位疫苗进行梳理,介绍了各类亚单位疫苗的抗原设计策略和佐剂选择、整体保护能力及研究进展,并对亚单位疫苗的应用及技术优势进行分析,期望能为亚单位疫苗研发及全球疫情防控提供参考。     

Phenotypes and Functions of SARS-CoV-2-Reactive T Cells

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), which is an ongoing pandemic disease. SARS-CoV-2-specific CD4⁺ and CD8⁺ T-cell responses have been detected and characterized not only in COVID-19 patients and convalescents, but also unexposed individuals. Here, we review the phenotypes and functions of SARS-CoV-2-specific T cells in COVID-19 patients and the relationships between SARS-CoV-2-specific T-cell responses and COVID-19 severity. In addition, we describe the phenotypes and functions of SARS-CoV-2-specific memory T cells after recovery from COVID-19 and discuss the presence of SARS-CoV-2-reactive T cells in unexposed individuals and SARS-CoV-2-specific T-cell responses elicited by COVID-19 vaccines. A better understanding of T-cell responses is important for effective control of the current COVID-19 pandemic.     

The immunodominant and neutralization linear epitopes for SARS-CoV-2

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SARS-CoV-2 associated COVID-19 in geriatric population: A brief narrative review

Coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has emerged as a fatal pandemic and has crushed even the world’s best healthcare systems. Globally, it has affected 40,373,228 individuals and resulted in 1,119,568 deaths as of October 19, 2020. Research studies have demonstrated that geriatric population is vastly vulnerable to COVID-19 morbidity and mortality given their age and preexisting chronic comorbidities such as cardiovascular disease, hypertension, diabetes mellitus, chronic pulmonary and chronic kidney disease The data regarding susceptibility of elderly population to COVID-19 is accruing and suggests that factors like age, gender, chronic comorbidity, inflammaging, immunosenescence and renin angiotensin system may be the contributing risk factors towards COVID-19 and associated mortality in elderly population. Based on updated scientific literature, this narrative review précises the clinical presentations and underlying risk factors that might be associated with COVID-19 morbidity in geriatric population and provides informed insights, and discusses clinical presentation, psychosocial impact, mortality and potential corticosteroid treatment and prevention strategies of COVID-19 in older adults.     

Genome composition and genetic characterization of SARS-CoV-2

SARS-CoV-2 is a type of Betacoronaviruses responsible for COVID-19 pandemic disease, with more than 1.745 million fatalities globally as of December-2020. Genetically, it is considered the second largest genome of all RNA viruses with a 5′ cap and 3′ poly-A tail. Phylogenetic analyses of coronaviruses reveal that SARS-CoV-2 is genetically closely related to the Bat-SARS Like-Corona virus (Bat-SL-Cov) with 96% whole-genome identity. SARS-CoV-2 genome consists of 15 ORFs coded into 29 proteins. At the 5′ terminal of the genome, we have ORF1ab and ORF1a, which encode the 1ab and 1a polypeptides that are proteolytically cleaved into 16 different nonstructural proteins (NSPs). The 3′ terminal of the genome represents four structural (spike, envelope, matrix, and nucleocapsid) and nine accessory (3a, 3b, 6, 7a, 7b, 8b, 9a, 9b, and orf10) proteins. As the number of COVID-19 patients increases dramatically worldwide, there is an urgent need to find a quick and sensitive diagnostic tool for controlling the outbreak of SARS-CoV-2 in the community. Today, molecular testing methods utilizing viral genetic material (e.g., PCR) represent the crucial diagnostic tool for the SARS-CoV-2 virus despite its low sensitivity in the early stage of viral infection. This review summarizes the genome composition and genetic characterization of the SARS-CoV-2.     

A trans-complementation system for SARS-CoV-2 recapitulates authentic viral replication without virulence

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Receptor-binding domain of SARS-CoV-2 spike protein efficiently inhibits SARS-CoV-2 infection and attachment to mouse lung

COVID-19, caused by a novel coronavirus, SARS-CoV-2, poses a serious global threat. It was first reported in 2019 in China and has now dramatically spread across the world. It is crucial to develop therapeutics to mitigate severe disease and viral spread. The receptor-binding domains (RBDs) in the spike protein of SARS-CoV and MERS-CoV have shown anti-viral activity in previous reports suggesting that this domain has high potential for development as therapeutics. To evaluate the potential antiviral activity of recombinant SARS-CoV-2 RBD proteins, we determined the RBD residues of SARS-CoV-2 using a homology search with RBD of SARS-CoV. For efficient expression and purification, the signal peptide of spike protein was identified and used to generate constructs expressing recombinant RBD proteins. Highly purified RBD protein fused with the Fc domain of human IgG showed potent anti-viral efficacy, which was better than that of a protein fused with a histidine tag. Intranasally pre-administrated RBD protein also inhibited the attachment of SARS-COV-2 to mouse lungs. These findings indicate that RBD protein could be used for the prevention and treatment of SARS-CoV-2 infection.     

A Comparative Study between Spanish and British SARS-CoV-2 Variants

The study of the interaction between the SARS-CoV-2 spike protein and the angiotensin-converting enzyme 2 (ACE2) receptor is key to understanding binding affinity and stability. In the present report, we sought to investigate the differences between two already sequenced genome variants (Spanish and British) of SARS-CoV-2. Methods: In silico model evaluating the homology, identity and similarity in the genome sequence and the structure and alignment of the predictive spike by computational docking methods. Results: The identity results between the Spanish and British variants of the Spike protein were 28.67%. This close correspondence in the results between the Spanish and British SARS-CoV-2 variants shows that they are very similar (99.99%). The alignment obtained results in four deletions. There were 23 nucleotide substitutions also predicted which could affect the functionality of the proteins produced from this sequence. The interaction between the binding receptor domain from the spike protein and the ACE2 receptor produces some of the mutations found and, therefore, the energy of this ligand varies. However, the estimated antigenicity of the British variant is higher than its Spanish counterpart. Conclusions: Our results indicate that minimal mutations could interfere in the infectivity of the virus due to changes in the fitness between host cell recognition and interaction proteins. In particular, the N501Y substitution, situated in the RBD of the spike of the British variant, might be the reason for its extraordinary infective potential.     

Humoral Immunity against SARS-CoV-2 and the Impact on COVID-19 Pathogenesis

It has been more than a year since severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first emerged. Many studies have provided insights into the various aspects of the immune response in coronavirus disease 2019 (COVID-19). Especially for antibody treatment and vaccine development, humoral immunity to SARS-CoV-2 has been studied extensively, though there is still much that is unknown and controversial. Here, we introduce key discoveries on the humoral immune responses in COVID-19, including the immune dynamics of antibody responses and correlations with disease severity, neutralizing antibodies and their cross-reactivity, how long the antibody and memory B-cell responses last, aberrant autoreactive antibodies generated in COVID-19 patients, and the efficacy of currently available therapeutic antibodies and vaccines against circulating SARS-CoV-2 variants, and highlight gaps in the current knowledge.     

Immune response and potential therapeutic strategies for the SARS-CoV-2 associated with the COVID-19 pandemic

Following onset of the first recorded case of Coronavirus disease 2019 (COVID-19) in December 2019, more than 269 million cases and over 5.3 million deaths have been confirmed worldwide. COVID-19 is a highly infectious pneumonia, caused by a novel virus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, it poses a severe threat to human health across the globe, a trend that is likely to persist in the foreseeable future. This paper reviews SARS-CoV-2 immunity, the latest development of anti-SARS-CoV-2 drugs as well as exploring in detail, immune escape induced by SARS-CoV-2. We expect that the findings will provide a basis for COVID-19 prevention and treatment.