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.     

Structural insights into the activity regulation of full-length non-structural protein 1 from SARS-CoV-2

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The current state of validated small molecules inhibiting SARS-CoV-2 nonstructural proteins

The current COVID-19 outbreak has had a profound influence on public health and daily life. Despite all restrictions and vaccination programs, COVID-19 still can lead to fatality due to a lack of COVID-19-specific treatments. A number of studies have demonstrated the feasibility to develop therapeutics by targeting underlying components of the viral proteome. Here we reviewed recently developed and validated small molecule inhibitors of SARS-CoV-2’s nonstructural proteins. We described the validation level of identified compounds specific for SARS-CoV-2 in the presence of in vitro and in vivo supporting data. The mechanisms of pharmacological activity, as well as approaches for developing improved SARS-CoV-2 NSP inhibitors have been emphasized.     

Binding of the SARS-CoV-2 envelope E protein to human BRD4 is essential for infection

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新型冠状病毒(SARS-CoV-2)蛋白靶位的生信分析

目前新型冠状病毒肺炎(COVID-19)疫情仍在全球肆虐,但尚无针对该病毒的治疗特效药.在此背景,以美国化学文摘社(Chemical Abstracts Service,CAS)提供的SARS-CoV-2病毒及宿主蛋白靶标为研究对象,运用基因功能富集、蛋白网络等方法进行生物信息分析.结果发现,人网格蛋白介导型内吞和依赖...     

In vivo structural characterization of the SARS-CoV-2 RNA genome identifies host proteins vulnerable to repurposed drugs

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SARS-CoV-2 NSP7和NSP8的研究进展

冠状病毒进入细胞后以基因组RNA作为转录本,翻译产生多聚蛋白,多聚蛋白水解后产生16种功能各异的非结构蛋白(Nonstructural Protein,NSP).其中,NSP7和NSP8对病毒的RNA复制过程和RNA聚合酶活性非常重要.对新型冠状病毒(Severe Acute Respiratory Syndrome ...     

Differential binding of SARS-CoV-2 Spike protein variants to its cognate receptor hACE2 using molecular modeling based binding analysis

The current emergence of novel coronavirus, SARS-CoV-2 and its ceaseless expansion worldwide has posed a global health emergency that has adversely affected the humans. With the entire world striving to understand the newly emerged virus, differences in morbidity and infection rate of SARS-CoV-2 have been observed across varied geographic areas, which have been ascribed to viral mutation and evolution over time. The homotrimeric Spike (S) glycoprotein on the viral envelope surface is responsible for binding, priming, and initiating infection in the host. Our phylogeny analysis of 1947 sequences of S proteins indicated there is a change in amino acid (aa) from aspartate (Group-A) to glycine (Group-B) at position 614, near the receptor- binding domain (RBD; aa positions 331-524). The two variants are reported to be in circulation, disproportionately across the world, with Group-A dominant in Asia and Group-B in North America. The trimeric, monomeric, and RBD of S protein of both the variant groups (A & B) were modeled using the Swiss-Model server and were docked with the human receptor angiotensin-converting enzyme 2 (hACE2) employing the PatchDock server and visualized in PyMol. Group-A S protein''s RBD bound imperceptibly to the two binding clefts of the hACE2 protein, on the other hand, Group-B S protein''s RBD perfectly interacted inside the binding clefts of hACE2, with higher number of hydrogen and hydrophobic interactions. This implies that the S protein''s amino acid at position 614 near the core RBD influences its interaction with the cognate hACE2 receptor, which may induce its infectivity that should be explored further with molecular and biochemical studies.     

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.     

新冠病毒中和单克隆抗体及纳米抗体研究进展北大核心CSCD

由严重急性呼吸系统综合征冠状病毒2型(severe acute respiratory syndrome coronavirus-2,SARS-CoV-2)引起的疾病被命名为新型冠状病毒肺炎(coronavirus disease 2019,COVID-19),是一种具有强传染性、高易感性、长潜伏期的传染病。病毒刺突蛋白受体结合结构域(receptor binding domain,RBD)和细胞血管紧张素转换酶2(angiotensin-converting enzyme 2,ACE2)之间的相互作用使得SARS-CoV-2顺利进入细胞。本文对SARS-CoV-2与ACE2的相关作用机制进行了简单概述,对目前针对SARS-CoV-2中和单克隆抗体、纳米抗体的最新研究进展进行了总结,探讨了新冠肺炎的发展过程和抗体药物的研究方向,以期为包括新冠肺炎在内的新发、突发传染病中和抗体药物的研发提供参考。     

Computational Identification of Small Interfering RNA Targets in SARS-CoV-2

With the epidemic of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) worldwide and in the absence of any effective vaccine, there is an urgent need to find a specific anti- SARS-CoV-2 agent. In this study, by analyzing the secondary structures of the SARS-CoV-2 genome (MN908947), several 21~25 base-long segments were obtained and selected as the potential targets of small interfering RNA duplexes. Moreover, it was also found that these targets are conserved among different strains. We hope the results will contribute to the pharmaceutical research and therapy of the SARS-CoV-2.     

一种基于荧光qPCR检测新型冠状病毒核酸的优化反应体系的建立及相关测试

为实时并快速地检出SARS-CoV-2冠状病毒RNA,对基于荧光定量聚合酶链式反应(Polymerasechain reaction,PCR)的反应体系进行了优化。结果表明,按照本实验提供的方法操作后,检测SARS-CoV-2冠状病毒所用的RNA样本的最小浓度稀释度可调至1/10000(初始值设为10ng/μL)。且用于检测COVID-19临床阳性样本所测得循环值(Cycle threshold,Ct)均低于35或40。其灵敏性测试结果也表明该方法的敏感性较好。同时在同等条件下,与目前市场上的COVID-19试剂盒的检测结果基本一致,并且检测循环数缩短2个单位。因此,本实验所建立的体系适用于前期临床诊断的筛查工作,为在医学上实现快速诊断提供了工具。     

The SARS-CoV-2 RNA interactome

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SARS-Coronavirus-2 Nsp13 Possesses NTPase and RNA Helicase Activities That Can Be Inhibited by Bismuth Salts

The ongoing outbreak of Coronavirus Disease 2019 (COVID-19) has become a global public health emergency. SARS-coronavirus-2 (SARS-CoV-2), the causative pat     

Translation landscape of SARS-CoV-2 noncanonical subgenomic RNAs

The ongoing COVID-19 pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with a positive-stranded RNA genome. Current proteomic studies of SARS-CoV-2 mainly focus on the proteins encoded by its genomic RNA (gRNA) or canonical subgenomic RNAs (sgRNAs). Here, we systematically investigated the translation landscape of SARS-CoV-2, especially its noncanonical sgRNAs. We first constructed a strict pipeline, named vipep, for identifying reliable peptides derived from RNA viruses using RNA-seq and mass spectrometry data. We applied vipep to analyze 24 sets of mass spectrometry data related to SARS-CoV-2 infection. In addition to known canonical proteins, we identified many noncanonical sgRNA-derived peptides, which stably increase after viral infection. Furthermore, we explored the potential functions of those proteins encoded by noncanonical sgRNAs and found that they can bind to viral RNAs and may have immunogenic activity. The generalized vipep pipeline is applicable to any RNA viruses and these results have expanded the SARSCoV-2 translation map, providing new insights for understanding the functions of SARS-CoV-2 sgRNAs.