Genetic tracing of HCoV-19 for the re-emerging outbreak of COVID-19 in Beijing,China

The ongoing pandemic of coronavirus disease 2019(COVID-19)caused by a novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2,also named as 2019-nCoV or HCoV-19)poses an unprecedented threat to public health(Zhu et al.,2020;Wang et al.,2020;Jiang et al.,2020).The novel HCoV-19 virus has rapidly spread into multiple countries across the world since it was first reported in December 2019.The World Health Organization(WHO)declared COVID-19 as a pandemic on 11th March 2020.As of 4th July,over 10 million confirmed COVID-19 cases have been reported in over 200 countries/regions with more than 0.5 million deaths,including 85,287 documented cases and 4,648 deaths in China(WHO,2020a).     

Measures for diagnosing and treating infections by a novel coronavirus responsible for a pneumonia outbreak originating in Wuhan,China

On 10 January 2020, a new coronavirus causing a pneumonia outbreak in Wuhan City in central China was denoted as 2019-nCoV by the World Health Organization (WHO). As of 24 January 2020, there were 887 confirmed cases of 2019-nCoV infection, including 26 deaths, reported in China and other countries. Therefore, combating this new virus and stopping the epidemic is a matter of urgency. Here, we focus on advances in research and development of fast diagnosis methods, as well as potential prophylactics and therapeutics to prevent or treat 2019-nCoV infection.     

Pathogenicity and transmissibility of 2019-nCoV—A quick overview and comparison with other emerging viruses

A zoonotic coronavirus, tentatively labeled as 2019-nCoV by the World Health Organization (WHO), has been identified as the causative agent of the viral pneumonia outbreak in Wuhan, China, at the end of 2019. Although 2019-nCoV can cause a severe respiratory illness like SARS and MERS, evidence from clinics suggested that 2019-nCoV is generally less pathogenic than SARS-CoV, and much less than MERS-CoV. The transmissibility of 2019-nCoV is still debated and needs to be further assessed. To avoid the 2019-nCoV outbreak turning into an epidemic or even a pandemic and to minimize the mortality rate, China activated emergency response procedures, but much remains to be learned about the features of the virus to refine the risk assessment and response. Here, the current knowledge in 2019-nCoV pathogenicity and transmissibility is summarized in comparison with several commonly known emerging viruses, and information urgently needed for a better control of the disease is highlighted.     

Repurposing FDA-approved drugs for SARS-CoV-2 through an ELISA-based screening for the inhibition of RBD/ACE2 interaction

Dear Editor, The ongoing coronavirus disease 2019(COVID-19)global pandemic is caused by a novel coronavirus,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),which instigates severe and often fatal symptoms.As of September 4th,2020,more than 26 million cases of COVID-19 and almost 900,000 deaths have been reported to WHO.Based on Kissler and colleagues'modeled projections of future viral transmission scenarios,a resurgence in SARS-CoV-2 could occur over the next five years(Kissler et al.,2020).Research and clinical trials are underway to develop vacci-nes and treatments for COVID-19,but there are currently no specific vaccines or treatments for COVID-19(www.who.int),and therapeutic and prophylactic interventions are urgently needed to combat the outbreak of SARS-CoV-2.Of partic-ular importance is the identification of drugs which are effective,less-intrusive,most socioeconomic,and ready-to-use.     

Pan-coronavirus fusion inhibitors as the hope for today and tomorrow

The last two decades of the 21st century have seen emerging zoonotic coronavirus(CoV)diseases,including severe acute respiratory syndrome(SARS)(Holmes 2003),Middle East respiratory syndrome(MERS)(Graham et al.,2013)and coronavirus disease 2019(COVID-19)(Jiang et al.,2020).     

The epidemic of 2019-novel-coronavirus (2019-nCoV) pneumonia and insights for emerging infectious diseases in the future

At the end of December 2019, a novel coronavirus, 2019-nCoV, caused an outbreak of pneumonia spreading from Wuhan, Hubei province, to the whole country of China, which has posed great threats to public health and attracted enormous attention around the world. To date, there are no clinically approved vaccines or antiviral drugs available for these human coronavirus infections. Intensive research on the novel emerging human infectious coronaviruses is urgently needed to elucidate their route of transmission and pathogenic mechanisms, and to identify potential drug targets, which would promote the development of effective preventive and therapeutic countermeasures. Herein, we describe the epidemic and etiological characteristics of 2019-nCoV, discuss its essential biological features, including tropism and receptor usage, summarize approaches for disease prevention and treatment, and speculate on the transmission route of 2019-nCoV.     

Epidemiological,Clinical and Serological Characteristics of Children with Coronavirus Disease 2019 in Wuhan: A Single-centered,Retrospective Study

In December 2019, SARS-CoV-2 was first detected in the samples obtained from three adult patients who suffered from an unknown viral pneumonia in Wuhan (Li et al. 2020). This unknown viral pneumonia is further named as coronavirus disease 2019 (COVID-19) by the World Health Organization. To date, the number of new COVID-19 cases has continued to skyrocket and the impact of SARS-CoV-2 on humans is far greater than any pathogen of this century in both breadth and depth. Previous studies have shown that adults with COVID-19 have symptoms of fever, dry cough, dyspnea, fatigue and lymphocytopenia. Moreover, COVID-19 is more likely to cause death in the elderly, especially those with chronic comorbidities (Huang et al. 2020). In Wuhan, more than 50, 000 COVID-19 cases have been confirmed, including over 780 pediatric patients, and only one child death case (Lu et al. 2020). Although the number of children cases was far fewer than that of adults, COVID-19 might endanger children's health and the information on children remains limited, especially in serological study. In the retrospective study, the investigators analyzed the epidemiological, clinical and serological characteristics of children with COVID-19 in Wuhan in the early stages of the outbreak, which might provide theoretical and practical help in controlling COVID-19 and similar emerging infectious diseases in the future.     

A global treatments for coronaviruses including COVID-19

In late December 2019 in Wuhan, China, several patients with viral pneumonia were identified as 2019 novel coronavirus (2019-nCoV). So far, there are no specific treatments for patients with coronavirus disease-19 (COVID-19), and the treatments available today are based on previous experience with similar viruses such as severe acute respiratory syndrome-related coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and Influenza virus. In this article, we have tried to reach a therapeutic window of drugs available to patients with COVID-19. Cathepsin L is required for entry of the 2019-nCoV virus into the cell as target teicoplanin inhibits virus replication. Angiotensin-converting-enzyme 2 (ACE2) in soluble form as a recombinant protein can prevent the spread of coronavirus by restricting binding and entry. In patients with COVID-19, hydroxychloroquine decreases the inflammatory response and cytokine storm, but overdose causes toxicity and mortality. Neuraminidase inhibitors such as oseltamivir, peramivir, and zanamivir are invalid for 2019-nCoV and are not recommended for treatment but protease inhibitors such as lopinavir/ritonavir (LPV/r) inhibit the progression of MERS-CoV disease and can be useful for patients of COVID-19 and, in combination with Arbidol, has a direct antiviral effect on early replication of SARS-CoV. Ribavirin reduces hemoglobin concentrations in respiratory patients, and remdesivir improves respiratory symptoms. Use of ribavirin in combination with LPV/r in patients with SARS-CoV reduces acute respiratory distress syndrome and mortality, which has a significant protective effect with the addition of corticosteroids. Favipiravir increases clinical recovery and reduces respiratory problems and has a stronger antiviral effect than LPV/r. currently, appropriate treatment for patients with COVID-19 is an ACE2 inhibitor and a clinical problem reducing agent such as favipiravir in addition to hydroxychloroquine and corticosteroids.     

Clinical Features and Treatment of 2019-nCov Pneumonia Patients in Wuhan: Report of A Couple Cases

正Dear Editor,Till January 20, 2020, the 2019-new coronavirus(2019-nCoV) has caused more than one hundred cases in Wuhan(WMHC 2020). During a retrospective study of recent pneumonia patients in our department, we found two patients who are likely being infected with the 2019-nCoV.     

Covid-19 pandemic outburst in Saudi Arabia: A glimpse

SynopsisSevere Acute Respiratory Syndrome Coronavirus2 (SARS-CoV2) provoked alertness globally. Existing pandemic eruption of infections with SARS-CoV2 has been phrased as coronavirus disease 2019 (covid-19). Worldwide pneumonia outburst attributable to new SARS-CoV2 alleged to be originated in Wuhan city of China and has affectation of enormous danger regarding civic wellbeing. As of 11 March 2020, international death toll owing to outburst of new coronavirus was approximately 3,800, and about 110,000 have been declared as confirmed cases. The novel SARS-CoV2 demonstrated competence with respect to human to human communication; therefore depicted exponential intensification of cases. As of March 23, there are 374,513 collective cases of global infections; more than 16,350 deaths and number of recovered cases is 101,554. Now Europe has turn out into new epicenter of lethal coronavirus.More than one third of the covid 19 cases are currently outside China. Presently Italy is one of worst hit countries followed by Spain. The rapid global widespread of novel covid-19 viruses lead to World Health Organization (WHO) to declare outbreak as pandemic. Given to seriousness of present scenario an accurate and rapid classification of noxious pathogenic virus is important which will lend a hand in opting for best fitting drugs. The screening program will aid saving people’s lives and help to put off the pandemic situation. The scientists and researchers should collaborate nationally and internationally to win the battle against novel covid-19. We aimed to represent covid 19 outburst scenario in general and Saudi Arabia in particular. This short review report very briefly highlights covid-19 syndromes; propagation; Middle East outburst, natural products as cure for viral diseases, probable psychosomatic effects, protective measures and Islamic wisdom. SARS-CoV2 is subsequent coronavirus outburst that perturbs Middle East, after SARS-CoV and MERS-CoV which has been originated in kingdom of Saudi Arabia in year 2002 and 2012 respectively. The report covers information and developments till 23rd of March 2020 on basis of current published data and studies published on different scientific web-pages.     

Molecular deconvolution of the neutralizing antibodies induced by an inactivated SARS-CoV-2 virus vaccine

Dear Editor, The rapid emergence and persistence of the pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) has had enormous impacts on global health and the economy.Effective vaccines against SARS-CoV-2 are urgently needed to control the coronavirus disease 2019(COVID-19) pandemic,and multiple vaccines have been found to be efficacious in preventing symptomatic COVID-19(Polack et al.,2020;Wu et al.,2020;Jones and Roy,2021).We have developed a traditional beta-propiolactone-inacti-vated aluminum hydroxide-adjuvanted whole-virion SARS-CoV-2 vaccine (BBIBP-CorV),which elicited protective immune responses in clinical trials (Wang et al.,2020;Xia et al.,2021).The vaccine has been granted conditional approvals or emergency use authorizations (EUAs) in China and other countries.     

Fish ACE2 is not susceptible to SARS-CoV-2

The ongoing pandemic of coronavirus disease 2019 (COVID-19) has reshaped our daily life and caused > 4 million deaths worldwide (https://covid19.who.int/). Although lockdown and vaccination have improved the situation in many countries, imported cases and sporadic outbreaks pose a constant stress to the prevention and control of COVID-19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent responsible for COVID-19, has a positive-sense single-stranded RNA genome of 30 kb (Coronaviridae Study Group of the International Committee on Taxonomy of Viruses, 2020). We and other groups have demonstrated that the SARS-CoV-2 could use the angiotensin-converting enzyme 2 (ACE2) as cell receptor, including orthologs of a broad range of animal species such as human, bats, ferrets, pigs, cats, and dogs (Hoffmann et al., 2020; Zhou et al., 2020; Liu et al., 2021). Although the evolutionary origin of SARS-CoV-2 can be linked to the discoveries of diverse coronaviruses related to SARS-CoV-2 in wild animals such as bats (Zhou et al., 2020; Wacharapluesadee et al., 2021) and pangolins (Liu et al., 2019; Lam et al., 2020), the direct origin of SARS-CoV-2 in humans remains unknown. In China, several sporadic outbreaks of COVID-19 in 2020 were linked to food in cold chain sold at trade markets, including salmon meat (http://www.nhc.gov.cn/xcs/yqtb/list_gzbd.shtml) (Yang et al., 2020). The detection of SARS-CoV-2 RNA on the surface of frozen meat for as long as 20 days has also been reported (Feng et al., 2021). A concern regarding the potential role of fish in SARS-CoV-2 transmission has also been raised. Therefore, we investigated the susceptibility of fish ACE2 to SARS-CoV-2.     

An integrated rapid nucleic acid detection assay based on recombinant polymerase amplification for SARS-CoV-2

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel coronavirus that causes the outbreak of coronavirus disease 2019 (COVID-19) (Li et al., 2020a). Viral nucleic acid testing is the standard method for the laboratory diagnosis of COVID-19 (Wu et al., 2020a; Zhu et al., 2020). Currently, a variety of qPCR-based detection kits are used for laboratory-based detection and confirmation of SARS-CoV-2 infection (Corman et al., 2020; Hussein et al., 2020; Ruhan et al., 2020; Veyer et al., 2020). Conventional qPCR involves virus inactivation, nucleic acid extraction, and qPCR amplification procedures. Therefore, the process is complicated, which usually takes longer than 2 h, and requires biosafety laboratories and professional staff. Thus, qPCR is not suitable for use in field or medical units. To reduce the operation steps, automatic integrated qPCR detection systems that combine nucleic acid extraction and qPCR amplification in a sealed cartridge were developed to detect viruses in clinical samples (Li et al., 2020b). However, the detection time is still longer than 1 h. Therefore, rapid nucleic acid detection systems are needed to further improve the detection efficiency.     

严重急性呼吸综合征冠状病毒2型 IgM / IgG、病毒核酸和白细胞介素6的联合检测在2019冠状病毒病诊断和治疗中的价值

探讨严重急性呼吸综合征冠状病毒2型(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)免疫球蛋白M(Immunoglobulin M,IgM)/免疫球蛋白G(Immunoglobulin G,IgG)、病毒核酸和白细胞介素6(interleukin 6, IL-6)的联合检测在2019冠状病毒病(coronavirus disease 2019, COVID-19)诊断和治疗中的临床价值。本研究按照《新型冠状病毒肺炎诊疗方案(试行第七版)》的标准收集了93例确诊病例(51例危重型、18例重型,15例轻型和9例普通型)和20例疑似病例(核酸检测阴性但临床症状和CT检测结果均符合标准)。选取110例儿科、妇科、肿瘤、血液和消化等疾病患者并排除COVID-19作为对照组。采用全自动化学发光免疫分析技术和电化学发光技术检测所有研究对象血清中SARS-CoV-2 IgM/IgG和IL-6。用实时荧光定量反转录聚合酶链反应对病例组和对照组的咽拭子进行SARS-CoV-2核酸检测。结果发现,血清IgM、IgG和IL-6在疑似病例中的阳性率分别为85%、75%和0%,在确诊病例中的阳性率分别为98.9%、95.7%和75.2%(其中危重型分别为100%、100%和100%,重型分别为94.4%、100%和97.9%,轻型分别为100%、93.3%和5%、普通型分别为100%、66.7%和0%)。IL-6和 SARS-CoV-2 IgM/IgG表达水平的改变与患者疾病的严重程度存在一定的关联性,差异有统计学意义(χ²＝273.51,χ²＝149.37;P＜0.05)。血清IL-6和SARS-CoV-2 IgM/IgG的联合检测可作为诊断和治疗COVID-19的监测指标,也可作为SARS-CoV-2核酸检测假阴性的有效互补。     

新型冠状病毒上海株(nCoV-SH01)的分离和鉴定

新型冠状病毒肺炎(coronavirus disease 2019,COVID-19)疫情对人类生命健康构成极大威胁。病毒的分离是构建新型冠状病毒(2019 novel coronavirus, 2019-nCoV)细胞感染模型和动物感染模型的基础。本研究利用冠状病毒易感的Vero E6细胞,从1例上海感染者的咽拭子中分离到一株2019-nCoV,命名为nCoV-SH01。对该毒株全基因组采用一代Sanger和二代Illumina法测序,发现该毒株与GenBank MN908947的同源性＞99.99%。免疫荧光检测显示,该毒株与COVID-19康复者的血清呈阳性反应。当nCoV-SH01感染Vero E6细胞后,导致典型的合胞体病变,细胞病变效应明显且进展迅速,提示nCoV-SH01可用于进一步建立2019-nCoV的细胞感染和动物感染模型,为开展致病性研究以及抗病毒药物和疫苗研发奠定了基础。     

广谱抗冠状病毒疫苗及抗冠状病毒多肽的研究进展

由严重急性呼吸综合征冠状病毒2型(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)感染引起的2019冠状病毒病(coronavirus disease 2019,COVID-19)暴发,给人类公共卫生安全和全球经济发展造成了严重威胁。疫苗和药物是防治疫情的重要手段,但目前研发的针对冠状病毒的疫苗和药物大多以SARS-CoV-2为靶点,该病毒若发生重大突变或出现新的高致病性冠状病毒,目前研发的有效疫苗或药物可能会无效,而且疫苗和新药的研发往往比较滞后,难以在疫情发生早期投入使用。因此,亟须研发高效、安全、广谱的冠状病毒疫苗和药物,以应对未来可能出现的冠状病毒疫情。本文对广谱冠状病毒疫苗和抗冠状病毒多肽的研究进展进行综述,期望为研发此类疫苗和药物提供参考。     

新型冠状病毒基因组结构与蛋白功能

2019年12月以来,武汉市暴发新型冠状病毒肺炎(coronavirus disease 2019,COVID-19)疫情并迅速蔓延全国,2020年1月30日被世界卫生组织(World Health Organization,WHO)列为“国际关注的突发公共卫生事件”(public health emergency of international concern,PHEIC)。核酸序列分析证明COVID-19由新型冠状病毒(2019 novel coronavirus,2019-nCoV)引起。2019-nCoV为正链单链RNA病毒,基因组长约30 kb,两端为非编码区,中间为非结构蛋白编码区和结构蛋白编码区。非结构蛋白编码区主要包括开放读码框架(open reading frame,ORF)1a和ORF1b基因,编码16个非结构蛋白(non-structural proteins,NSP),即NSP1～16。结构蛋白编码区主要编码刺突(spike,S)蛋白、包膜(envelope,E)蛋白、膜(membrane,M)蛋白和核衣壳(nucleocapsid,N)蛋白。深入了解2019-nCoV基因组的结构和蛋白功能,将为2019-nCoV相关的病毒溯源、复制增殖、致病免疫、药物与疫苗研发以及当前疫情的防控提供有力的支撑。     

Vaccine development and therapeutic design for 2019-nCoV/SARS-CoV-2: Challenges and chances

The ongoing outbreak of the recently emerged 2019 novel coronavirus (nCoV), which has seriously threatened global health security, is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with high morbidity and mortality. Despite the burden of the disease worldwide, still, no licensed vaccine or any specific drug against 2019-nCoV is available. Data from several countries show that few repurposed drugs using existing antiviral drugs have not (so far) been satisfactory and more recently were proven to be even highly toxic. These findings underline an urgent need for preventative and therapeutic interventions designed to target specific aspects of 2019-nCoV. Again the major factor in this urgency is that the process of data acquisition by physical experiment is time-consuming and expensive to obtain. Scientific simulations and more in-depth data analysis permit to validate or refute drug repurposing opportunities predicted via target similarity profiling to speed up the development of a new more effective anti-2019-nCoV therapy especially where in vitro and/or in vivo data are not yet available. In addition, several research programs are being developed, aiming at the exploration of vaccines to prevent and treat the 2019-nCoV. Computational-based technology has given us the tools to explore and identify potentially effective drug and/or vaccine candidates which can effectively shorten the time and reduce the operating cost. The aim of the present review is to address the available information on molecular determinants in disease pathobiology modules and define the computational approaches employed in systematic drug repositioning and vaccine development settings for SARS-CoV-2.     

Re-detectable positive SARS-CoV-2 RNA tests in patients who recovered from COVID-19 with intestinal infection

Dear Editor,Severe acute respiratory syndrome coronavirus 2(SARSCoV-2),a novel coronavirus that causes Coronavirus Disease 2019(COVID-19)(Yang and Wang,2020),has spread to more than 200 countries and infected more than 9,000,000 people as of Jun 2020.Tens of thousands of patients with COVID-19 have recovered and been discharged from hospital.However,there are reports of recovered patients who subsequently tested positive for SARSCoV-2 after discharge(re-detectable positive,RP)(An et al.,2020;Lan et al.,2020),and this has led to increasing focus on the mechanism(s)underlying RP.