Drug repurposing against coronavirus disease 2019 (COVID-19): A review

Since December 2019, severe acute respiratory syndrome coronavirus 2 has been found to be the culprit in the coronavirus disease 2019 (COVID-19), causing a global pandemic. Despite the existence of many vaccine programs, the number of confirmed cases and fatalities due to COVID-19 is still increasing. Furthermore, a number of variants have been reported. Because of the absence of approved anti-coronavirus drugs, the treatment and management of COVID-19 has become a global challenge. Under these circumstances, drug repurposing is an effective method to identify candidate drugs with a shorter cycle of clinical trials. Here, we summarize the current status of the application of drug repurposing in COVID-19, including drug repurposing based on virtual computer screening, network pharmacology, and bioactivity, which may be a beneficial COVID-19 treatment.     

SARS-CoV-2: Camazotz's Curse

The world is currently face to face with a pandemic which is spreading rapidly across the globe caused by SARS-CoV-2, a strain of Coronaviruses (CoVs) belonging to subgenus Sarbecovirus of genus Betacoronavirus. World Health Organisation (WHO) on 11 Feb 20 named this disease caused by SARS-CoV-2 as Covid-19. This pandemic is spreading rapidly and more than 20,00,000 cases have occurred globally. The human Coronaviruses discovered in 1960s were considered potentially harmless endemic viruses with seasonal distribution before late 2002. The CoVs are found in a large number of domestic and wild animals and birds. The first pandemic caused by Coronavirus caused by SARS-CoV was recognized in the late 2002 in Guangdong Province and resulted in widespread morbidity and mortality. This was followed by MERS-CoV which began in 2012 in the Arabian peninsula with multiple outbreaks related to it in various parts of the globe. Various studies have suggested how these viruses made their entry from their natural reservoir bats via intermediate host like civets and camels in case of SARS-CoV and MERS-CoV respectively. The intermediate host of the SARS-CoV-2 still needs to be established. The SARS-CoV-2 has 96.2% similarity to the bat Severe Acute Respiratory Syndrome related-Coronavirus (SARSr-CoV RaTG13). SARS-CoV-2 has been found to be more distant in relation to SARS-CoV (79%) and MERS-CoV (50%). At the whole genome sequence level pangolin CoV and SARSr-CoV RaTG13 show 91.02% and 96.2% similarity with SARS-CoV-2 but the S1 subunit of spike protein of pangolin CoV is more closely related to SARS-CoV-2 than SARSr-CoV RaTG13. The genetic analysis of the currently circulating strains of the pandemic have shown 99.98-100% similarity in their genomes implying a recent shift to humans. The animal source of SARS-CoV-2 needs to be identified to implement control measures in the present pandemic. Also, how the virus moves interspecies will help predict and prevent future pandemics.     

全球冠状病毒研究概况及热点分析

目的：分析全球冠状病毒研究概况及热点,为冠状病毒研究及防控提供数据和情报支撑。方法：基于Web of Science和MEDLINE数据库,利用文献计量和知识图谱等方法,对全球范围内冠状病毒研究的发展趋势、研究群体的竞争力、研究热点及前沿等进行深入分析。结果：自2003年以来,冠状病毒的研究热度不断提升,中国和美国在冠状病毒研究领域的生产力和影响力均领先于世界其他各国,传染病学、病毒学、微生物学是冠状病毒研究的重点学科领域,近20年来冠状病毒的研究主要围绕SARS-CoV、MERS-CoV和畜禽类冠状病毒三大类展开。结论：未来2～3年内将会出现以COVID-19为重点的研究高峰,跨国家、跨机构、跨学科的协同攻关将会大大提升COVID-19的研究效率和缩短攻关周期。     

Structural basis of SARS-CoV-2 3CLpro and anti-COVID-19 drug discovery from medicinal plants

The recent pandemic of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has raised global health concerns. The viral 3-chymotrypsin-like cysteine protease (3CL^pro) enzyme controls coronavirus replication and is essential for its life cycle. 3CL^pro is a proven drug discovery target in the case of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Recent studies revealed that the genome sequence of SARS-CoV-2 is very similar to that of SARS-CoV. Therefore, herein, we analysed the 3CL^pro sequence, constructed its 3D homology model, and screened it against a medicinal plant library containing 32,297 potential anti-viral phytochemicals/traditional Chinese medicinal compounds. Our analyses revealed that the top nine hits might serve as potential anti- SARS-CoV-2 lead molecules for further optimisation and drug development process to combat COVID-19.     

Chapter of Gastroenterologists professional guidance for management of patients with liver disease in Singapore during the COVID-19 pandemic

In this paper, we aim to provide professional guidance to clinicians who are managing patients with chronic liver disease during the current coronavirus disease 2019 (COVID-19) pandemic in Singapore. We reviewed and summarised the available relevant published data on liver disease in COVID-19 and the advisory statements that were issued by major professional bodies, such as the American Association for the Study of Liver Diseases and European Association for the Study of the Liver, contextualising the recommendations to our local situation.     

In Silico Screening of Potential Spike Glycoprotein Inhibitors of SARS-CoV-2 with Drug Repurposing Strategy

Objective: To select potential molecules that can target viral spike proteins, which may potentially interrupt the interaction between the human angiotension-converting enzyme 2(ACE2) receptor and viral spike protein by virtual screening. Methods: The three-dimensional(3 D)-coordinate file of the receptor-binding domain(RBD)-ACE2 complex for searching a suitable docking pocket was firstly downloaded and prepared. Secondly, approximately 15,000 molecular candidates were prepared, including US Food and Drug Administration(FDA)-approved drugs from Drug Bank and natural compounds from Traditional Chinese Medicine Systems Pharmacology(TCMSP), for the docking process. Then, virtual screening was performed and the binding energy in Autodock Vina was calculated. Finally, the top 20 molecules with high binding energy and their Chinese medicine(CM) herb sources were listed in this paper. Results: It was found that digitoxin, a cardiac glycoside in Drug Bank and bisindigotin in TCMSP had the highest docking scores. Interestingly, two of the CM herbs containing the natural compounds that had relatively high binding scores, Forsythiae fructus and Isatidis radix, are components of Lianhua Qingwen(莲花清瘟), a CM formula reportedly exerting activity against severe acute respiratory syndrome(SARS)-Cov-2. Moreover, raltegravir, an HIV integrase inhibitor, was found to have a relatively high binding score. Conclusions: A class of compounds, which are from FDA-approved drugs and CM natural compounds, that had high binding energy with RBD of the viral spike protein. Our work provides potential candidates for other researchers to identify inhibitors to prevent SARS-Co V-2 infection, and highlights the importance of CM and integrative application of CM and Western medicine on treating COVID-19.     

新型冠状病毒对循环系统影响的研究进展

新型冠状病毒肺炎(coronavirus disease 2019,COVID-19)是由新型冠状病毒(SARS-CoV-2)引起的,以发热、咳嗽及呼吸困难为主要临床症状的一种可在人群中广泛传播的疾病。截至目前,2019新型冠状病毒已在全球范围内造成大流行,随着国内疫情防治工作的有效开展,以及对于新型冠状病毒肺炎的认识与研究不断加深,发现很多新冠肺炎患者出现以循环系统损害症状为首发或继发的临床症状。SARS-CoV-2可直接通过血管紧张素转换酶2 (angiotensin converting enzyme 2,ACE2)受体损伤心肌细胞,也可以通过异常激活免疫系统、释放大量细胞因子从而导致急、慢性的心肌损伤。当心功能受损严重时,可能会通过RAS系统影响到肾脏功能,从而导致患者同时出现心脏和肾脏损害的临床表现。此外,对于COVID-19患者来说,还存在着动、静脉血栓栓塞的风险。本文结合近日来公布的新冠肺炎病例的资料和各团队最新的研究发现,对新型冠状病毒对于循环系统影响的研究进展做一简要概述,以期为进一步了解新型冠状病毒感染对循环系统的损害提供帮助。      

基因技术在新型冠状病毒肺炎等重大疾病防治中的作用

基因技术是上世纪生命科学具有划时代意义的发明。总体上对疾病的病因、病理机制、药物研发、疫苗和抗体研发多方面具有十分重要的地位,但基因技术因其设计原理及应用对象的差别也存在不同程度的局限性。具体到特定疾病如2019年底爆发的SARS-CoV-2疫情,其优缺点主要表现在:首先对确定病原体起了关键作用;其次对新型冠状病毒肺炎的诊断及愈后判断也有重要参考价值;同时,作为新冠肺炎的确诊指标也呈现出一定的局限性。作者根据长期从事基因技术研究的经验及对本次疫情基因检测结果的分析,提出充分利用相关基因检测技术的优势,发挥其在尽快确定新冠肺炎感染者中的重要辅助作用。     

SARS-CoV-2暴露剂量与COVID-19潜伏期及病情发展趋势的相关性研究

尽管SARS-CoV-2暴露剂量和暴露者机体抵抗力都是受多种因素影响难以确定的变量,但COVID-19的发生是SARS-CoV-2暴露剂量与暴露者机体抵抗力相互作用的结果。本文通过比较中国湖北内外发病情形、湖北之外其他省市不同日期COVID-19发病的潜伏期、以及散发病例与聚集性发病情形,发现SARS-CoV-2感染率高低与疫情时程及潜伏期均相关,显示SARS-CoV-2暴露剂量与是否发病、以及发病后的严重程度均可能具有相关性。从而提示COVID-19的治疗,需要对潜伏期偏短的患者提防其重症化和死亡风险。     

高龄老年新型冠状病毒肺炎患者的血液学特征

目的 总结75岁及以上高龄老年新冠肺炎患者的血液学特征,以指导老年患者的诊断和早期治疗.方法 回顾性分析2020年2月3日～3月30日在武汉火神山医院收治确诊为新冠肺炎的高龄老年患者(年龄≥75岁)的病例资料.根据临床分型分为普通型组和重型组,比较两组患者的各项检查指标.重型组根据预后情况分为重型治愈组和重型死亡组,分...     

The infodemics of COVID-19 amongst healthcare professionals in India

BackgroundThere is a deluge of information and misinformation about COVID-19. The present survey was conducted to explore the sources of information /misinformation for healthcare professionals from India.MethodsA cross-sectional online survey using snowballing technique was conducted from 24 Mar to 10 Apr 2020. The questionnaire was pretested and developed using standard techniques. It was circulated among medical students and physicians. Data were analysed using the STATA software.ResultsData of 758 participants were analysed. A total of 255 (33.6%) medical students, 335 (44.2%) nonspecialists and 168 (22.1%) specialists participated. The most common source of formal and informal information was official government websites and online news, respectively. A total of 517 (68.2%) participants accepted receiving misinformation. Social media and family and friends were the most common sources of misinformation. Seventy-two percent of participants agreed that spread of information helped to contain COVID-19, but more than that 75% agreed to having received inaccurate information. Seventy-four percent of respondents felt the need for regulation of information during such times; 26% and 33% felt that information about COVID-19 made them feel uncomfortable and distracts routine decision-making, respectively, and 50% felt it was difficult to differentiate correct from incorrect information about COVID-19.ConclusionThe study explored the sources of information and misinformation and found a high prevalence of misinformation, especially from social media. We suggest the need to better manage the flow of information so that it can be an effective weapon against SARS-CoV2. There is a need for doctors to adapt to the changing times of infodemics accompanying pandemics.     

广西首起新型冠状病毒肺炎家庭聚集性疫情分析

目的 报道广西首次发生的一起家庭聚集性新型冠状病毒肺炎疫情的流行病学特征和临床特点。方法 详细收集和分析一家庭10名成员中7名感染新型冠状病毒的流行病学、临床表现、实验室检查和放射影像学。结果 2020年1月18日居住在武汉的6名成员从武汉来到南宁,并与居住在南宁的4名成员一起生活。6名居住在武汉的成员有4名感染新型冠状病毒。4名近期没有去过武汉居住在南宁的成员有3名感染新型冠状病毒。7名患者年龄中位数37岁,其中包括一名11岁儿童。从出现症状到确诊的时间为1~7 d。临床症状包括干咳（42.85%）、肌痛（42.85%）、发热（28.57%）、疲乏（28.57%）、咽痛（14.28%）、头晕（14.28%）、鼻塞（14.28%）,没有患者出现呼吸困难。炎症标志物C反应蛋白和降钙素原正常。淋巴细胞计数减少3例（42.85%）,CD4⁺T淋巴细胞降低1例（16.67%）。5名患者肺部出现磨玻璃样病灶。结论 新型冠状病毒肺炎可在家庭成员之间互相传播。我们需要重视家庭人与人之间的传染,加强家庭聚集性病例的管理。     

新型冠状病毒肺炎恢复期核酸复阳合并肺隐球菌感染1例分析

目的 分析1例新型冠状病毒肺炎恢复期核酸复阳合并肺隐球菌患者被误诊为肺恶性肿瘤,经手术病理证实肺隐球菌的治疗过程及转归,为该类患者的诊治提供依据.方法 选择海南省人民医院感染科收治的1例新型冠状病毒肺炎恢复期核酸复阳合并肺隐球菌感染患者,分析其一般情况、临床表现、实验室检查、诊断、治疗及预后等临床资料.结果 患者在恢复...     

Structural elucidation of SARS-CoV-2 vital proteins: Computational methods reveal potential drug candidates against main protease,Nsp12 polymerase and Nsp13 helicase

Recently emerged SARS-CoV-2 caused a major outbreak of coronavirus disease 2019 (COVID-19) and instigated a widespread fear, threatening global health safety. To date, no licensed antiviral drugs or vaccines are available against COVID-19 although several clinical trials are under way to test possible therapies. During this urgent situation, computational drug discovery methods provide an alternative to tiresome high-throughput screening, particularly in the hit-to-lead-optimization stage. Identification of small molecules that specifically target viral replication apparatus has indicated the highest potential towards antiviral drug discovery. In this work, we present potential compounds that specifically target SARS-CoV-2 vital proteins, including the main protease, Nsp12 RNA polymerase and Nsp13 helicase. An integrative virtual screening and molecular dynamics simulations approach has facilitated the identification of potential binding modes and favourable molecular interaction profile of corresponding compounds. Moreover, the identification of structurally important binding site residues in conserved motifs located inside the active site highlights relative importance of ligand binding based on residual energy decomposition analysis. Although the current study lacks experimental validation, the structural information obtained from this computational study has paved way for the design of targeted inhibitors to combat COVID-19 outbreak.     

基于专利信息的全球新冠病毒检测技术竞争态势分析

通过深度挖掘专利信息,从研发趋势、主要国家市场竞争力和创新主体的专利布局、技术热点、高价值专利等角度,对全球SARS-CoV-2检测技术研发现状及竞争态势进行分析。结合我国现阶段的短板弱项,提出我国创新主体应加大投入力度、加快研究进度、促进学科融合、拓宽合作网络、加强开放创新等建议,以期为今后的研究和专利布局提供借鉴。     

Role of anticoagulation in lowering the mortality in hospitalized covid-19 patients: Meta-analysis of available literature

Objectives:To reducing the risk of venous thromboembolic (VTE) events and subsequent mortality in covid-19 patients is still a matter of research. This systematic review and meta-analysis serve the purpose of comparing the mortality associated with the intensity of anticoagulation in patients admitted with covid-19.Methods:A total of 7120 patients were recruited in 11 studies comparing using prophylactic anticoagulants against therapeutic anticoagulants.Results:Our study showed that using prophylactic anticoagulants was associated with a 42% reduction in mortality compared to therapeutic anticoagulants (OR 0.58 (95% CI:0.676-0.499), p=0.000). Also, we assessed mortality in patients using no anticoagulants against using prophylactic anticoagulants. A total of 6069 patients were recruited in 4 studies in which 2 studies significantly favored prophylactic anticoagulants in terms of reducing mortality. Cumulatively, the meta-analysis showed that using prophylactic anticoagulants was associated with a 5% reduction in mortality but without any statistical significance: (OR 1.049 [95% CI 1.237 - 0.865]) (p=0.626).Conclusion:Our meta-analysis favors using prophylactic anticoagulation in covid-19 patients reduces all-cause mortality in comparison to therapeutic anticoagulation however the impact on mortality when compared with no anticoagulation was not significant.PROSPERO Number: CRD42021257320     

多部位样本核酸检测持续阳性的新型冠状病毒肺炎患者1例分析

目前新型冠状病毒肺炎（COVID-19）正在我国及世界其他国家流行,患者感染病毒后的临床症状不一,甚至呈现为无症状感染状态,这给整个疫情的防控提出了更高的要求。新型冠状病毒（SARS-CoV-2）核酸检测作为COVID-19诊断的主要手段,在抗击疫情的过程中发挥着重要的作用,因此备受关注。本文报告一例无明显消化道症状,但粪便及肛拭子核酸检测持续阳性的COVID-19病例。患者为武汉某大学在校学生,在校期间即出现呼吸道症状,后放假回家,因病情加重而就诊入院,根据病情发展和诊疗需要,该患者进行了多次核酸检测,在症状明显好转,咽拭子核酸检测转阴后,其痰液、肛拭子及粪便样本的核酸检测仍持续阳性,由此,讨论多部位样本核酸检测对COVID-19诊疗的临床意义,并探讨疫情防控策略。     

3例危重型新型冠状病毒肺炎患者临床分析

目的 分析海南省人民医院成功诊治的3例危重型新型冠状病毒肺炎（coronavirus disease 2019,COVID-19）的临床特征及治疗,为诊治危重型COVID-19患者提供科学依据。方法 对2020年1月底至2月初成功救治的3例危重型COVID-19患者进行回顾性分析。结果 3例患者中,男性2例,女性1例,平均年龄42岁。2例为二代病例,1例为本土病例。平均住院天数16.67 d,发病初期均有发热,2例有咳嗽,进展期出现重症肺炎。2例患者白细胞计数正常,1例白细胞计数、中性粒细胞计数减少,2例中性粒细胞计数升高,3例淋巴细胞计数减少, C-反应蛋白升高,恢复期淋巴细胞计数恢复正常。患者胸部影像学提示双肺渗出影、部分实变及磨玻璃影。入院后经积极抗病毒、抗感染、免疫调节、营养支持、CRRT、机械通气结合中医调理,全部康复出院。结论 危重型COVID-19患者病情进展快,病程中合并多种并发症,早期诊断并及时综合支持治疗是治疗成功的关键。     

广州市205例新型冠状病毒肺炎临床特征

目的 回顾分析广州市新型冠状病毒肺炎病例的流行病史、临床症状、影像学以及实验室指标改变,从而为临床快速筛查及诊治提供参考依据。方法 采集2020年1月21日—2020年2月5日在广州市八人民医院收治的205例新型冠状病毒肺炎病例的病史资料,分析其流行病史、临床症状、影像学及实验室指标的变化特点。结果 205例患者中男性101例（49%）,女性104例（51%）,年龄范围2~83岁,平均（48.64±16.74）岁,其中20岁及以下仅有5人。194例（95%）有疫区居住或旅游等接触史。55例（27%）有慢性基础疾病,以高血压41例（20%）,糖尿病11例（5%）,心血管疾病8例（4%）为主。入院时发热175例（85%）,其余临床症状以干咳80例（39%）、咳嗽咳痰54例（26%）,咽部不适55例（27%）,畏寒50例（24%）多见。实验室检查发现白细胞正常或偏低197例（96%）,淋巴细胞正常或偏低202例（98%）。中性粒细胞百分比升高24例（12%）,C反应蛋白升高85例（42%）,降钙素原升高73例（37%）,56例样本中血清淀粉样蛋白A升高44例（79%）。D二聚体、凝血功能以及肝肾功能部分病例异常。计算机化X线体层照相术显示192例（94%）有肺炎表现。结论 广州市新型冠状病毒肺炎病例男女比例接近。儿童或青少年感染少,以中老人,有基础病为主。首发症状以发热为主,白细胞和淋巴细胞绝对值正常或偏低,对新型冠状病毒肺炎的早期筛查和诊断有重要的辅助作用。计算机化X线体层照相术对新型冠状病毒肺炎的初步临床诊断价值大。     

从一对夫妻患者的诊治过程探讨2019冠状病毒病(COVID-19)疑似患者的管理

观察2例2019冠状病毒病（COVID-19）疑似患者诊断、治疗以及隔离管理的过程,结合文献分析COVID-19疑似患者的临床特征和管理重点。COVID-19是由严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染所致的疾病,SARS-CoV-2具有很强的传染性,甚至无症状感染者也可能传播病毒。SARS-CoV-2可通过接触传播、飞沫传播,并可能通过气溶胶传播。在临床发热门诊的患者管理中,准确识别并管理好疑似患者,采取严格的隔离措施,对院内感染的防控极为重要。