Potential covalent drugs targeting the main protease of the SARS-CoV-2 coronavirus.

靶向SARS-CoV-2 冠状病毒主要蛋白酶的潜在共价药物。

  • 影响因子:5.94
  • DOI:10.1093/bioinformatics/btaa224
  • 作者列表:"Liu S","Zheng Q","Wang Z
  • 发表时间:2020-06-01

MOTIVATION:Since December 2019, the newly identified coronavirus SARS-CoV-2 has caused a massive health crisis worldwide and resulted in over 70 000 COVID-19 infections so far. Clinical drugs targeting SARS-CoV-2 are urgently needed to decrease the high fatality rate of confirmed COVID-19 patients. Traditional de novo drug discovery needs more than 10 years, so drug repurposing seems the best option currently to find potential drugs for treating COVID-19. RESULTS:Compared with traditional non-covalent drugs, covalent drugs have attracted escalating attention recent years due to their advantages in potential specificity upon careful design, efficiency and patient burden. We recently developed a computational protocol named as SCAR (steric-clashes alleviating receptors) for discovering covalent drugs. In this work, we used the SCAR protocol to identify possible covalent drugs (approved or clinically tested) targeting the main protease (3CLpro) of SARS-CoV-2. We identified 11 potential hits, among which at least six hits were exclusively enriched by the SCAR protocol. Since the preclinical or clinical information of these identified drugs is already available, they might be ready for being clinically tested in the treatment of COVID-19. CONTACT:senliu.ctgu@gmail.com.


动机: 自 2019 年 12 月以来,新发现的冠状病毒SARS-CoV-2 在全球范围内造成了大规模的健康危机,迄今已导致超过 70 000 新型冠状病毒肺炎感染。临床迫切需要针对SARS-CoV-2 的药物来降低确诊新型冠状病毒肺炎患者的高病死率。传统的新生药物发现需要 10 多年的时间,因此药物再利用似乎是目前寻找治疗新型冠状病毒肺炎的潜在药物的最佳选择。 结果: 与传统的非共价药物相比,由于共价药物在精心设计、效率和患者负担方面的潜在特异性优势,近年来受到了越来越多的关注。我们最近开发了一种名为SCAR (空间冲突缓解受体) 的计算方案,用于发现共价药物。在这项工作中,我们使用SCAR方案来确定可能的共价药物 (批准或临床试验) 靶向SARS-CoV-2 的主要蛋白酶 (3CLpro)。我们确定了 11 个潜在的点击,其中至少有 6 个点击被SCAR方案独家富集。由于这些鉴定药物的临床前或临床信息已经可用,因此它们可能已准备好用于治疗新型冠状病毒肺炎的临床试验。 联系人: senliu.ctgu@gmail.com。



作者列表:["Lim J","Jeon S","Shin HY","Kim MJ","Seong YM","Lee WJ","Choe KW","Kang YM","Lee B","Park SJ"]

METHODS::Since mid-December of 2019, coronavirus disease 2019 (COVID-19) infection has been spreading from Wuhan, China. The confirmed COVID-19 patients in South Korea are those who came from or visited China. As secondary transmissions have occurred and the speed of transmission is accelerating, there are rising concerns about community infections. The 54-year old male is the third patient diagnosed with COVID-19 infection in Korea. He is a worker for a clothing business and had mild respiratory symptoms and intermittent fever in the beginning of hospitalization, and pneumonia symptoms on chest computerized tomography scan on day 6 of admission. This patient caused one case of secondary transmission and three cases of tertiary transmission. Hereby, we report the clinical findings of the index patient who was the first to cause tertiary transmission outside China. Interestingly, after lopinavir/ritonavir (Kaletra, AbbVie) was administered, β-coronavirus viral loads significantly decreased and no or little coronavirus titers were observed.

作者列表:["Zhang W","Du RH","Li B","Zheng XS","Yang XL","Hu B","Wang YY","Xiao GF","Yan B","Shi ZL","Zhou P"]

METHODS::In December 2019, a novel coronavirus (2019-nCoV) caused an outbreak in Wuhan, China, and soon spread to other parts of the world. It was believed that 2019-nCoV was transmitted through respiratory tract and then induced pneumonia, thus molecular diagnosis based on oral swabs was used for confirmation of this disease. Likewise, patient will be released upon two times of negative detection from oral swabs. However, many coronaviruses can also be transmitted through oral-fecal route by infecting intestines. Whether 2019-nCoV infected patients also carry virus in other organs like intestine need to be tested. We conducted investigation on patients in a local hospital who were infected with this virus. We found the presence of 2019-nCoV in anal swabs and blood as well, and more anal swab positives than oral swab positives in a later stage of infection, suggesting shedding and thereby transmitted through oral-fecal route. We also showed serology test can improve detection positive rate thus should be used in future epidemiology. Our report provides a cautionary warning that 2019-nCoV may be shed through multiple routes.

翻译标题与摘要 下载文献
作者列表:["Cheng ZJ","Shan J"]

METHODS::There is a current worldwide outbreak of a new type of coronavirus (2019-nCoV), which originated from Wuhan in China and has now spread to 17 other countries. Governments are under increased pressure to stop the outbreak spiraling into a global health emergency. At this stage, preparedness, transparency, and sharing of information are crucial to risk assessments and beginning outbreak control activities. This information should include reports from outbreak sites and from laboratories supporting the investigation. This paper aggregates and consolidates the virology, epidemiology, clinical management strategies from both English and Chinese literature, official news channels, and other official government documents. In addition, by fitting the number of infections with a single-term exponential model, we report that the infection is spreading at an exponential rate, with a doubling period of 1.8 days.