新型冠状病毒疫苗安全性与有效性研究进展

自2019年底至今,由严重急性呼吸综合征冠状病毒2(SARS-CoV-2)导致的新型冠状病毒(新冠病毒)肺炎(COVID-19)在全球范围内广泛传播,并成为导致死亡的主要原因之一.为减轻新冠病毒对公共卫生、经济和社会的影响,全球疫苗研发机构均在积极研发疫苗,包括灭活疫苗、病毒载体疫苗、蛋白亚基疫苗、mRNA疫苗和DNA...     

COVID-19疫苗研发与临床应用进展

新型冠状病毒(severe acute respiratory syndrome coronavirus-2, SARS-CoV-2)已在全球包括中国在内的220多个国家蔓延。随着对SARS-CoV-2的病毒分子结构和发病机制的研究不断深入，各种针对新型冠状病毒肺炎(coronavirus disease 2019,COVID-19)的预防策略和治疗方案，都在进行积极的探索。多个国家或地区的医药企业和科研机构也积极进行COVID-19疫苗的研发。目前全球有300多种候选COVID-19疫苗正在研究中，已有10余种疫苗进入临床Ⅲ期试验阶段或紧急使用授权。我国已有5款COVID-19疫苗获批使用，包括3款灭活疫苗、1款5型腺病毒载体疫苗和1款蛋白重组疫苗(CHO细胞)。牛津大学/阿斯利康、强生研发的COVID-19疫苗均属于腺病毒载体疫苗。辉瑞和BioNTech研发的mRNA疫苗、Moderna研发的mRNA疫苗的紧急使用授权也为新冠肺炎疫情防控提供潜在前景。近期，我国学者研究出针对Delta-Omicron嵌合RBD二聚体蛋白疫苗，有效预防Delta和Omicron感染小鼠引起的肺炎。该...     

新型冠状病毒肺炎疫苗研究进展概述

摘要：新型冠状病毒（SARS-CoV-2）自发现以来就引起了人们的广泛关注,其感染引发的肺炎（COVID-19）疫情在多国发生,SARS-CoV-2对全球公共卫生安全造成了巨大威胁。目前COVID-19病理机制尚不明确,尚未有治疗COVID-19的特效药物,科学认识SARS-CoV-2和尽快研制针对该病毒的有效疫苗成为近期的研究热点,部分疫苗已进入Ⅲ临床试验阶段。本文主要从SARS-CoV-2的病原学特性、感染机制及其疫苗研究现状等方面进行综述,以便为其后续研究及防治提供参考。     

新型冠状病毒疫苗研发进展

目的 综述新型冠状病毒(SARS-CoV-2)疫苗的研究进展.方法 通过查找国内外关于SARS-CoV-2疫苗研发的文献资料,从SARS-CoV-2的结构特点,针对SARS-CoV-2疫苗研发主要使用的五种技术路线(重组蛋白疫苗、病毒载体疫苗、核酸疫苗、灭活疫苗和减毒活疫苗)及其具有代表性的疫苗进行介绍.结果 截止至2...     

新型冠状病毒肺炎治疗药物研发进展

自新型冠状病毒(SARS-CoV-2)疫情暴发以来,全球感染人数不断增加,医疗形势十分严峻,应急情况下创新药物研发和对已上市药物进行治疗新型冠状病毒肺炎(COVID-19)新适应证开发,成为寻找COVID-19特效治疗药物和最佳治疗方案的必由之路.目前已发现的血管紧张素转换酶2(ACE2)介导SARS-CoV-2入侵宿...     

天然产物来源的抗SARS-CoV-2药物研究进展

广谱高效的小分子药物是应对新型冠状病毒感染(COVID-19)及未来可能爆发疫情的重要武器。天然产物是药物先导化合物的重要来源,在抗COVID-19的药物研发中得到了广泛关注。本文综述了抗新型冠状病毒(SARS-CoV-2)药物的关键靶点和具有抗SARS-CoV-2活性的天然产物的研究进展,以期为抗SARS-CoV-2药物的研发提供参考。     

新型冠状病毒SARS-CoV-2及抗COVID-19药物研究进展

新型冠状病毒(SARS-CoV-2)感染引发的肺炎(COVID-19)疫情严重威胁广大人民群众身体健康和生命安全,对我国的经济发展、社会稳定和对外交往产生重大影响。由于新型冠状病毒的传染性强、传播速度快、致死率较高,尚无有效疫苗和药物来防治,因此针对该病毒的疫苗与药物研发显得尤为迫切。主要围绕COVID-19的病毒来源、传播途径、临床症状和防控治疗措施,以及目前抗COVID-19药物的研究进展进行综述。     

既往病毒性呼吸道传染疾病研究对抗COVID-19药物研发的启示

新型冠状病毒肺炎(COVID-19)疫情严重威胁人类的健康,并对世界经济造成了巨大损失。COVID-19是急性爆发性疾病,目前尚无靶向治疗特效药或疫苗上市,主要是对症支持治疗。由于时间紧迫,市场急需,这给医药领域的新药研发带来了巨大挑战。针对2019新型冠状病毒(SARS-CoV-2),充分借鉴既往的病毒(如流感病毒、SARS病毒、MERS病毒、埃博拉病毒等)引起的病毒性呼吸道传染疾病的防治理论和经验,快速形成有效的药物研发方案,是医药工业界应对新突发传染病的重要使命和有力抓手。本文综述了SARS-Co V-2与其他既往流行性病毒引起的急性呼吸道传染性疾病的发现、疫情蔓延和防治,剖析了病毒感染的发病机制,总结了既往病毒感染及防治药物的研究进展,以期为COVID-19的药物研发提供思路和启发。     

新型冠状病毒肺炎临床治疗药物最新研究进展

新型冠状病毒肺炎(coronavirus disease 2019,COVID-19)正在世界范围内流行.作为冠状病毒,新型冠状病毒(SARS-CoV-2)和严重急性呼吸综合征冠状病毒(SARS-CoV)都通过人血管紧张素转化酶2(ACE2)受体侵入宿主细胞.面对疫情异常严峻的现状,目前尚缺乏疫苗和尚无特异性针对该病毒...     

ACE2与新型冠状病毒肺炎的心肾损伤

由新型冠状病毒(Severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)感染引起的新型冠状病毒肺炎(Coronavirus disease 2019,COVID-19)不仅可以诱发典型的呼吸系统疾病,也能导致心肾系统等相关疾病。SARS-CoV-2的受体为血管紧张素转换酶2(Angiotensin-converting enzyme 2,ACE2)。本文通过阐述ACE2在心脏和肾脏中的作用,分析SARS-CoV-2感染引起患者心肾损伤的可能机制,为临床治疗COVID-19及研发抗SARS-CoV-2药物提供参考依据。     

Coronavirus disease 2019 (COVID-19): current status and future perspectives

Coronavirus disease 2019 (COVID-19) originated in the city of Wuhan, Hubei Province, Central China, and has spread quickly to 72 countries to date. COVID-19 is caused by a novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [previously provisionally known as 2019 novel coronavirus (2019-nCoV)]. At present, the newly identified SARS-CoV-2 has caused a large number of deaths with tens of thousands of confirmed cases worldwide, posing a serious threat to public health. However, there are no clinically approved vaccines or specific therapeutic drugs available for COVID-19. Intensive research on the newly emerged SARS-CoV-2 is urgently needed to elucidate the pathogenic mechanisms and epidemiological characteristics and to identify potential drug targets, which will contribute to the development of effective prevention and treatment strategies. Hence, this review will focus on recent progress regarding the structure of SARS-CoV-2 and the characteristics of COVID-19, such as the aetiology, pathogenesis and epidemiological characteristics.     

Structure genomics of SARS-CoV-2 and its Omicron variant: drug design templates for COVID-19

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has brought an unprecedented public health crisis and persistently threatens to humanity. With tireless efforts from scientists around the world, understanding of the biology of coronavirus has been greatly enhanced over the past 2 years. Structural biology has demonstrated its powerful impact on uncovering structures and functions for the vast majority of SARS-CoV-2 proteins and guided the development of drugs and vaccines against COVID-19. In this review, we summarize current progress in the structural biology of SARS-CoV-2 and discuss important biological issues that remain to be addressed. We present the examples of structure-based design of Pfizer’s novel anti-SARS-CoV-2 drug PF-07321332 (Paxlovid), Merck’s nucleotide inhibitor molnupiravir (Lagevrio), and VV116, an oral drug candidate for COVID-19. These examples highlight the importance of structure in drug discovery to combat COVID-19. We also discussed the recent variants of Omicron and its implication in immunity escape from existing vaccines and antibody therapies.     

Current COVID-19 vaccine candidates: Implications in the Saudi population

AimThe purpose of this review is to discuss the current status of local and international efforts undergoing clinical trials aiming at developing a Coronavirus Disease-2019 (COVID-19) vaccine, and to highlight the anticipated challenges of this vaccine globally and in Saudi Arabia.Present FindingsCOVID-19 vaccine development efforts started in early January 2020 when Chinese scientists shared the Coronavirus genomic sequence in public domain. Approximately 321 research groups initiated the search for a vaccine, out of which 41 have reached phase I/II trails and 11 reached phase-III clinical trials, including approved vaccines for early to limited use. Out of these projects are two labs in the Kingdom of Saudi Arabia still in early stages of development of a COVID-19 vaccine. Several vaccine attempts are being tested from traditional, attenuated virus methods, to new nucleic acid-based designs. However, no vaccine has yet completed clinical trials and reached public domain.In spite of the challenges faced during previous vaccine trials, researchers have found that Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19 is structurally similar to the (SARS-CoV-1) and the Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV), which caused epidemics in 2003 and 2012 respectively. Both SARS strains show identical affinity towards the type-II alveolar pneumocytes angiotensin converting enzyme-2 (ACE-2) receptor binding domains and therefore, similar pathogenicity. The race to develop the vaccine is predominantly for individuals at high risk of developing the infection, i.e. population groups who are most susceptible to experiencing fatal symptoms of the coronavirus. These include patients with comorbidities, above the age of 60 years and people at risk of contracting large viral loads, such as healthcare providers caring for critical admissions in in-patient wards, Intensive Care Units and Emergency Room settings.SummaryMany different vaccine strategies are under development throughout different stages of the research timeline; however, it is estimated that none will show favorable results before end of 2020. For any immunization or interventional prevention/therapy system to reach the public and patients at high risk, it needs to undergo multiple phase trials to ensure safety and effectiveness. In this scoping review we aim to map the literature on COVID-19 vaccines and provide recommendations related to gaps in research, applicability and expected challenges for implementation of nationwide vaccination in Saudi Arabia.     

Intranasal vaccines for SARS-CoV-2: From challenges to potential in COVID-19 management

Unlike conventional Coronavirus 2019 (COVID-19) vaccines, intranasal vaccines display a superior advantage because the nasal mucosa is often the initial site of infection. Preclinical and clinical studies concerning intranasal immunization elicit high neutralizing antibody generation and mucosal IgA and T cell responses that avoid severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in both; the upper and lower respiratory tract. A nasal formulation is non-invasive with high appeal to patients. Intranasal vaccines enable self-administration and can be designed to survive at ambient temperatures, thereby simplifying logistical aspects of transport and storage. In this review, we provide an overview of nasal vaccines with a focus on formulation development as well as ongoing preclinical and clinical studies for SARS-CoV-2 intranasal vaccine products.     

新型冠状病毒刺突蛋白结构及其疫苗研发

新型冠状病毒肺炎大流行在全球范围内造成严重的公共卫生危机。为预防新型冠状病毒（severe acute respiratory syndrome coronavirus 2,SARS-CoV-2）对健康带来的不利影响,不同类型、不同生产工艺的SARS-CoV-2疫苗相继被研发,包括减毒活疫苗、核酸疫苗、病毒载体疫苗、灭活疫苗和重组蛋白疫苗等,而病毒表面的刺突蛋白是SARS-CoV-2疫苗的研究热点。此文主要介绍SARS-CoV-2刺突蛋白的结构、功能与免疫学特性,以及SARS-CoV-2疫苗的研究情况、安全性、适用性等,并讨论潜在问题解决措施。     

Current approaches used in treating COVID-19 from a molecular mechanisms and immune response perspective

Coronavirus disease 2019 (COVID-19), which is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared by the World Health Organization (WHO) as a global pandemic on March 11, 2020. SARS-CoV-2 targets the respiratory system, resulting in symptoms such as fever, headache, dry cough, dyspnea, and dizziness. These symptoms vary from person to person, ranging from mild to hypoxia with acute respiratory distress syndrome (ARDS) and sometimes death. Although not confirmed, phylogenetic analysis suggests that SARS-CoV-2 may have originated from bats; the intermediary facilitating its transfer from bats to humans is unknown. Owing to the rapid spread of infection and high number of deaths caused by SARS-CoV-2, most countries have enacted strict curfews and the practice of social distancing while awaiting the availability of effective U.S. Food and Drug Administration (FDA)-approved medications and/or vaccines. This review offers an overview of the various types of coronaviruses (CoVs), their targeted hosts and cellular receptors, a timeline of their emergence, and the roles of key elements of the immune system in fighting pathogen attacks, while focusing on SARS-CoV-2 and its genomic structure and pathogenesis. Furthermore, we review drugs targeting COVID-19 that are under investigation and in clinical trials, in addition to progress using mesenchymal stem cells to treat COVID-19. We conclude by reviewing the latest updates on COVID-19 vaccine development. Understanding the molecular mechanisms of how SARS-CoV-2 interacts with host cells and stimulates the immune response is extremely important, especially as scientists look for new strategies to guide their development of specific COVID-19 therapies and vaccines.     

Highly pathogenic coronaviruses: thrusting vaccine development in the spotlight

Coronaviruses (CoVs) are a large family of viruses that cause illness ranging from the common cold to more severe diseases such as Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) has caused major public health crises. There have been more than 4,400,000 reported cases of COVID-2019 and more than 300,000 reported deaths to date (16/05/2020). SARS-CoV, MERS-CoV and SARS-CoV-2 have attracted widespread global attention due to their high infectivity and pathogenicity. To date, there is no specific treatment proven effective against these viral infectious diseases. Vaccination is considered one of the most effective strategies to prevent viral infections. Therefore, the development of effective vaccines against highly pathogenic coronaviruses is essential. In this review, we will briefly describe coronavirus vaccine design targets, summarize recent advances in the development of coronavirus vaccines, and highlight current adjuvants for improving the efficacy of coronavirus vaccines.     

Neuropathophysiology of coronavirus disease 2019: neuroinflammation and blood brain barrier disruption are critical pathophysiological processes that contribute to the clinical symptoms of SARS-CoV-2 infection

Inflammopharmacology - Coronavirus disease 2019 (COVID-19) is caused by the novel SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) first discovered in Wuhan, Hubei province, China in...     

Revisiting potential druggable targets against SARS-CoV-2 and repurposing therapeutics under preclinical study and clinical trials: A comprehensive review

Coronavirus disease-19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is one of the most contagious diseases in human history that has already affected millions of lives worldwide. To date, no vaccines or effective therapeutics have been discovered yet that may successfully treat COVID-19 patients or contain the transmission of the virus. Scientific communities across the globe responded rapidly and have been working relentlessly to develop drugs and vaccines, which may require considerable time. In this uncertainty, repurposing the existing antiviral drugs could be the best strategy to speed up the discovery of effective therapeutics against SARS-CoV-2. Moreover, drug repurposing may leave some vital information on druggable targets that could be capitalized in target-based drug discovery. Information on possible drug targets and the progress on therapeutic and vaccine development also needs to be updated. In this review, we revisited the druggable targets that may hold promise in the development of the anti-SARS-CoV-2 agent. Progresses on the development of potential therapeutics and vaccines that are under the preclinical studies and clinical trials have been highlighted. We anticipate that this review will provide valuable information that would help to accelerate the development of therapeutics and vaccines against SARS-CoV-2 infection.     

Delayed Cutaneous Hypersensitivity Reaction to Vaxzevria (ChAdOx1-S) Vaccine against SARS-CoV-2

Recently, an increasing number of cases with delayed cutaneous reaction after immunization with mRNA-based vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported. This adverse reaction, which is considered a delayed-type or T cell-mediated hypersensitivity reaction, has been described for the Moderna (mRNA-1273) and Comirnaty (Pfizer/BioNTech, BNT162b2) vaccines. We describe a delayed large local cutaneous reaction in a patient who received the viral vector vaccine Vaxzevria (ChAdOx1-S, AstraZeneca). The time course and clinical symptoms of delayed skin reaction after mRNA vaccines have a similar pattern that we recognized in our patient after Vaxzevria vaccination. This phenomenon has not been described in the Vaxzevria clinical trials and is to our knowledge the first report of this adverse reaction to a vector-based SARS-CoV-2 vaccine. With this, we hope to raise awareness about delayed injection site reactions that also occur after viral vector vaccines and to encourage additional reporting and patient education regarding the cutaneous reactions after coronavirus disease 2019 (COVID-19) vaccination.