您当前的位置: 首页 > 资源详情

Science,8月20日,Masitinib is a broad coronavirus 3CL inhibitor that blocks replication of SARS-CoV-2

编译者:YUTING发布时间:Aug 28, 2021点击量:253 来源栏目:最新研究

In January 2020, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified as the causative agent of a new respiratory syndrome that was later named COVID-19 (1). The virus has rapidly spread throughout the world, causing an ongoing pandemic, with millions of deaths (2). SARS-CoV-2 is a member of Coronaviridae, a family of enveloped, single-strand, positive-sense RNA viruses (3). This family is composed of both human and animal pathogens, including two other emerging human pathogens [SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV)] as well as four endemic human viruses that are the second most common cause of the common cold (HCoV-OC43, 229E, NL63, and HKU1) (4).

Upon entry into the host cell cytoplasm, the viral genome is translated into roughly 30 proteins. Of these, 16 are initially translated as two polyproteins that must be cleaved into the individual viral proteins for infection to proceed. This cleavage is mediated by two virally encoded proteases: the main viral protease, known as Mpro, 3CLpro, or nonstructural protein 5 (nsp5); and a second protease known as the papain-like protease, PLpro, a domain within nsp3 (3). There is interest in developing de novo inhibitors to target these proteases (5–10), but this is a lengthy process.

Although several vaccines received emergency use authorization from health authorities worldwide and are being deployed, it will take a long time to vaccinate the world population, and the emergence of viral escape mutants that render vaccines ineffective remains a possibility. Therefore, there is a continued need for new treatment options for COVID-19, as well as for broad-spectrum antivirals that could be used against future emerging viruses. Remdesivir, an RNA-dependent RNA-polymerase inhibitor, has been reported to shorten COVID-19 hospitalization times (11), but it failed a large clinical trial in hospitalized patients (12) and its efficacy is unclear.

Drug-repurposing screens have been used to identify safe-in-human drugs with potential anti–SARS-CoV-2 properties (9, 13, 14). Repurposed drugs that have existing clinical data on the effective dose, treatment duration, side effects, and toxicity could be rapidly translated into the treatment of patients.

We screened a library of 1900 clinically used drugs, either approved for human use or with extensive safety data in humans (phase 2 or 3 clinical trials), for their ability to inhibit infection of A549 cells by OC43. We chose OC43 because it is a human pathogen that belongs to the same clade of beta coronaviruses as SARS-CoV-2 and can be studied under “regular” biosafety conditions, as well as in an attempt to discover broad-spectrum anti-coronavirus drugs that would be beneficial against SARS-CoV-2 and future emerging coronaviruses. One day after plating, cells were infected at a multiplicity of infection (MOI) of 0.3 and incubated at 33°C for 1 hour, and drugs were added to a final concentration of 10 μM. Cells were then incubated at 33°C for 4 days, fixed, and stained for the presence of the viral nucleoprotein (Fig. 1A). We imaged the cells at day zero (after drug addition) and day four (after staining) to determine the effect of the drugs on cell growth and OC43 infection.

提供服务:导出本资源
  1. 1 Nature,11月10日,Initial whole-genome sequencing and analysis of the host genetic contribution to COVID-19 severity and susceptibility
  2. 2 11月10日_研究人员分析宿主基因对COVID-19严重程度和易感性的影响
  3. 3 11月11日_新冠药物Remestemcel-L二期临床的中期分析结果积极
  4. 4 11月11日_CDC呼吁制定通用口罩规定以减少新冠传播
  5. 5 SSRN,2月20日,Dynamics of the Latest 2019 Novel Coronavirus Disease Epidemic in China: A Descriptive Study
  6. 6 SSRN,2月20日,Mental Health Problems and Social Media Exposure During COVID-19 Outbreak
  7. 7 SSRN,2月20日,Evaluating Incidence and Impact Estimates of the Coronavirus Outbreak from Official and Non-Official Chinese Data Sources
  8. 8 SSRN,2月20日,Clinical Characteristics and Treatment of Patients Infected with COVID-19 in Shishou, China
  9. 9 Nature,11月10日,Mobility network models of COVID-19 explain inequities and inform reopening
  10. 10 1月27日_Nature报道中国新型冠状病毒最新研究进展:病毒传播速度有多快?
  1. 1 10月11日_SARS-CoV-2变体对mRNA疫苗诱导的免疫反应的影响
  2. 2 10月11日_SARS-CoV-2变体对mRNA疫苗诱导的免疫反应的影响
  3. 3 Medicalxpress,10月11日,Vaccines prevent severe COVID, even from Delta: study
  4. 4 10月11日_疫苗接种可预防严重COVID-19
  5. 5 PR Newswire,10月11日,INOVIO Expands INNOVATE Phase 3 for INO-4800, its DNA Vaccine Candidate for COVID-19, to include Colombia following Regulatory Authorization
  6. 6 10月11日_INOVIO扩展其COVID-19疫苗INO-4800的3期研究
  7. 7 ACCESSWIRE,10月11日,NanoViricides Announces COVID-19 Clinical Drug Candidate NV-CoV-2 was Effective Against SARS-CoV-2, Further Demonstrating Its Broad-Spectrum Pan-Coronavirus Activity
  8. 8 10月11日_NV-CoV-2具有广谱的抗冠状病毒活性
  9. 9 CIDRAP,10月11日,Merck applies for approval of first COVID-19 antiviral pill
  10. 10 10月11日_默沙东向FDA申请首款COVID-19抗病毒药丸的EUA

版权所有@2017中国科学院文献情报中心

制作维护:中国科学院文献情报中心信息系统部地址:北京中关村北四环西路33号邮政编号:100190