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

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Current advances in the development of SARS-CoV-2 vaccines

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is now a global pandemic that has wreaked havoc globally, which has put a heavy toll on public health, lives, and the world economy. Vaccination is considered as one of the greatest successes in medical history. Based on prior experience with the development of SARS-CoV vaccines, all COVID-19 vaccines must be subjected to the tests for protective effects and harmful risks derived from antibody-dependent enhancement that may contribute to augmented infectivity and/or eosinophilic infiltration. The SARS-CoV-2 vaccine is now being developed urgently in several different ways. China is regarded as one of the world''s leading countries in SARS-CoV-2 vaccine development, up to date the last inactivated vaccine international clinical (Phase III) trial was launched in the United Arab Emirates by Sinopharm China National Biotec Group (CNBG). In this review, we outline the current status of vaccine development against clinically relevant SARS-CoV-2 strains, anticipating that such attempts would help create efficacious and sage SARS-CoV-2 vaccines.     

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.     

An Infectious cDNA Clone of SARS-CoV-2

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新型冠状病毒SARS-CoV-2研究进展

在武汉发生的由新型冠状病毒SARS-CoV-2引发的人类冠状病毒病COVID-19,仅仅2个多月时间在我国及国际上70多个国家出现迅速传播,致病和死亡率高,人类生命受到了极大威胁。一些科学家火速投入研究,对SARS-CoV-2的来源和进化、形态特征和基因结构、感染和致病分子机制开展深入研究,取得了重大进展,为科学防控COVID-19提供了重要依据。根据上述研究的基础,文中对COVID-19病毒疫苗、抗体和抑制剂研发提出了设想,在研究防控COVID-19核心技术上具有一定的参考价值。     

Infection and Rapid Transmission of SARS-CoV-2 in Ferrets

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SARS-CoV-2 evolution in an immunocompromised host reveals shared neutralization escape mechanisms

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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。     

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.     

Low-impact social distancing interventions to mitigate local epidemics of SARS-CoV-2

Many jurisdictions implemented intensive social distancing to suppress SARS-CoV-2 transmission. The challenge now is to mitigate the ongoing COVID-19 epidemic without overburdening economic and social activities. An agent-based model simulated the population of King County, Washington. SARS-CoV-2 transmission probabilities were estimated by fitting simulated to observed hospital admissions. Interventions considered included encouraging telecommuting, reducing contacts to high-risk persons, and reductions to contacts outside of the home, among others. Removing all existing interventions would result in nearly 42,000 COVID-19 hospitalizations between June 2020 and January 2021, with peak hospital occupancy exceeding available beds 6-fold. Combining interventions is predicted to reduce total hospitalizations by 48% (95% CI, 47–49%), with peak COVID-19 hospital occupancy of 70% of total beds. Targeted school closures can further reduce the peak occupancy. Combining low-impact interventions may mitigate the course of the COVID-19 epidemic, keeping hospital burden within the capacity of the healthcare system.     

Genome sequence analysis of nsp15 from SARS-CoV-2

SARS-CoV-2 (Severe Acute Respiratory Syndrome), a causative agent of COVID-19 disease created a pandemic situation worldwide. Nsp15 is a uridine specific endoribonuclease encoded by the genome of SARS-CoV-2. It plays important role in processing viral RNA and, thus evades the host immune system. Therefore, it is of interest to identify mutants of nsp15 amongst Asian SARS-CoV-2 isolates, where a total of 1795 mutations, from 7793 sequences of Asia submitted till 31st January 2022, amongst which A231V, H234Y, K109N, K259R and S261A mutations were found frequent. Hence, we report data on the predicted secondary structure of wild type form followed by hydropathy plot, physiochemical properties, Ramachandran plot, B-cell epitopes prediction and protein modeling of wild type and mutant of nsp15 protein. Data shows that nsp15 of SARS-CoV-2 is a pontential candidate for the development of vaccine to control the infections of SARS-CoV-2.     

ORF3a of SARS-CoV-2 promotes lysosomal exocytosis-mediated viral egress

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Genomic Epidemiology of SARS-CoV-2 in Pakistan

COVID-19 has swept globally and Pakistan is no exception. To investigate the initial introductions and transmissions of the SARS-CoV-2 in Pakistan, we performed the largest genomic epidemiology study of COVID-19 in Pakistan and generated 150 complete SARS-CoV-2 genome sequences from samples collected from March 16 to June 1, 2020. We identified a total of 347 mutated positions, 31 of which were over-represented in Pakistan. Meanwhile, we found over 1000 intra-host single-nucleotide variants (iSNVs). Several of them occurred concurrently, indicating possible interactions among them or coevolution. Some of the high-frequency iSNVs in Pakistan were not observed in the global population, suggesting strong purifying selections. The genomic epidemiology revealed five distinctive spreading clusters. The largest cluster consisted of 74 viruses which were derived from different geographic locations of Pakistan and formed a deep hierarchical structure, indicating an extensive and persistent nation-wide transmission of the virus that was probably attributed to a signature mutation (G8371T in ORF1ab) of this cluster. Furthermore, 28 putative international introductions were identified, several of which are consistent with the epidemiological investigations. In all, this study has inferred the possible pathways of introductions and transmissions of SARS-CoV-2 in Pakistan, which could aid ongoing and future viral surveillance and COVID-19 control.     

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,     

Genomic chronicle of SARS-CoV-2: a mutational analysis with over 1 million genome sequences

Use of information technologies to analyse big data on SARS-CoV-2 genome provides an insight for tracking variations and examining the evolution of the virus. Nevertheless, storing, processing, alignment and analyses of these numerous genomes are still a challenge. In this study, over 1 million SARS-CoV-2 genomes have been analysed to show distribution and relationship of variations that could enlighten development and evolution of the virus. In all genomes analysed in this study, a total of over 215M SNVs have been detected and average number of SNV per isolate was found to be 21.83. Single nucleotide variant (SNV) average is observed to reach 31.25 just in March 2021. The average variation number of isolates is increasing and compromising with total case numbers around the world. Remarkably, cytosine deamination, which is one of the most important biochemical processes in the evolutionary development of coronaviruses, accounts for 46% of all SNVs seen in SARS-CoV-2 genomes within 16 months. This study is one of the most comprehensive SARS-CoV-2 genomic analysis study in terms of number of genomes analysed in an academic publication so far, and reported results could be useful in monitoring the development of SARS-CoV-2.     

Characteristics of asymptomatic patients with SARS-CoV-2 infection in Jinan,China

Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) is continuously and rapidly circulating at present. Asymptomatic patients have been proven to be contagious and thus pose a significant infection control challenge. Here we describe the characteristics of asymptomatic patients with SARS-CoV-2 infection in Jinan, Shandong province, China. A total of 47 patients with confirmed COVID-19 were recruited. Among them, 11 patients were categorized as asymptomatic cases. We found that the asymptomatic patients in Jinan were relatively young and were mainly clustered cases. The laboratory indicators and lung lesion on chest CT were mild. No special factors were found accounting for the presence or absence of symptoms. The presence of asymptomatic patients increased the difficulty of screening. It is necessary to strengthen the identification of such patients in the future.