Repurposing Antiviral Protease Inhibitors Using Extracellular Vesicles for Potential Therapy of COVID-19.
- 作者列表："Kumar S","Zhi K","Mukherji A","Gerth K
:In January 2020, Chinese health agencies reported an outbreak of a novel coronavirus-2 (CoV-2) which can lead to severe acute respiratory syndrome (SARS). The virus, which belongs to the coronavirus family (SARS-CoV-2), was named coronavirus disease 2019 (COVID-19) and declared a pandemic by the World Health Organization (WHO). Full-length genome sequences of SARS-CoV-2 showed 79.6% sequence identity to SARS-CoV, with 96% identity to a bat coronavirus at the whole-genome level. COVID-19 has caused over 133,000 deaths and there are over 2 million total confirmed cases as of April 15th, 2020. Current treatment plans are still under investigation due to a lack of understanding of COVID-19. One potential mechanism to slow disease progression is the use of antiviral drugs to either block the entry of the virus or interfere with viral replication and maturation. Currently, antiviral drugs, including chloroquine/hydroxychloroquine, remdesivir, and lopinavir/ritonavir, have shown effective inhibition of SARS-CoV-2 in vitro. Due to the high dose needed and narrow therapeutic window, many patients are experiencing severe side effects with the above drugs. Hence, repurposing these drugs with a proper formulation is needed to improve the safety and efficacy for COVID-19 treatment. Extracellular vesicles (EVs) are a family of natural carriers in the human body. They play a critical role in cell-to-cell communications. EVs can be used as unique drug carriers to deliver protease inhibitors to treat COVID-19. EVs may provide targeted delivery of protease inhibitors, with fewer systemic side effects. More importantly, EVs are eligible for major aseptic processing and can be upscaled for mass production. Currently, the FDA is facilitating applications to treat COVID-19, which provides a very good chance to use EVs to contribute in this combat.
: 一月份，到 2020 年，中国卫生机构报道爆发新型coronavirus-2 (CoV-2) 可导致严重急性呼吸道症候群 (传染性非典型肺炎).该病毒，属于冠状病毒病毒家族 (SARS-CoV-2)，被命名为冠状病毒病毒疾病 2019 (新型冠状病毒肺炎) 宣布为大流行病世卫组织.传染性非典型肺炎-CoV-2 的全基因组序列在全基因组水平上传染性非典型肺炎-CoV的序列同源性为 79.6%，与蝙蝠冠状病毒的序列同源性为 96%。截至 2020 年 4 月 15 日，新型冠状病毒肺炎已造成超过 133,000 人死亡，超过 200万确诊病例。由于缺乏对新型冠状病毒肺炎的了解，目前的治疗计划仍在调查中。延缓疾病进展的一个潜在机制是使用抗病毒药物阻断病毒进入或干扰病毒复制和成熟。目前，抗病毒药物，包括氯喹/羟氯喹、雷米地韦和洛匹那韦/利托那韦，在体外显示出有效抑制SARS-CoV-2。由于需要的高剂量和狭窄的治疗窗，许多患者正在经历上述药物的严重副作用。因此，需要通过适当的配方来重新利用这些药物，以提高新型冠状病毒肺炎治疗的安全性和有效性。细胞外囊泡 (EVs) 是人体内的一个天然载体家族。它们在细胞间通信中起着关键作用。EVs可以作为独特的药物载体递送蛋白酶抑制剂来治疗新型冠状病毒肺炎。EVs可以提供蛋白酶抑制剂的靶向递送，全身副作用更少。更重要的是，EVs有资格进行主要的无菌处理，并且可以进行大规模生产。目前，FDA正在促进治疗新型冠状病毒肺炎的应用，这为使用电动汽车在这场战斗中做出贡献提供了一个很好的机会。
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.
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.
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.