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1. chinaXiv:202002.00081 [pdf]

SARS-coronavirus-2 nsp13 possesses NTPase and RNA helicase activities

Shu, Ting; Huang, Muhan; Wu, Di; Ren, Yujie; Zhang, Xueyi; Han, Yang; Mu, Jingfang; Wang, Ruibing; Qiu, Yang; Zhang, Ding-Yu; Zhou, Xi
Subjects: Biology >> Virology

The ongoing outbreak of Coronavirus Disease 2019 (COVID-19) has become a global pandemic and crisis. SARS-coronavirus-2 (SARS-CoV-2), the causative pathogen of COVID-19, is a positive-sense single-stranded RNA virus belonging to the family Coronaviridae. For RNA viruses, virus-encoded RNA helicases have long been recognized to play pivotal roles during viral life cycles by facilitating the correct folding and replication of viral RNAs. Here, our studies show that SARS-CoV-2-encoded nonstructural protein 13 (nsp13) possesses the nucleoside triphosphate hydrolase (NTPase) and RNA helicase activities that can hydrolyze all types of NTPs and unwind RNA helices dependently of the presence of NTP, and further characterize the biochemical characteristics of these two enzymatic activities associated with SARS-CoV-2 nsp13. Moreover, we found that some bismuth salts could effectively inhibit both the NTPase and RNA helicase activities of SARS-CoV-2 nsp13 in a dose-dependent manner. Thus, our findings demonstrate the NTPase and helicase activities of SARS-CoV-2 nsp13, which may play an important role in SARS-CoV-2 replication and serve as a target for antivirals.

submitted time 2020-04-19 Hits12989Downloads1323 Comment 0

2. chinaXiv:202003.00026 [pdf]

Effective Treatment of Severe COVID-19 Patients with Tocilizumab

Xu, Xiaoling; Han, Mingfeng; Li, Tiantian; Sun, Wei; Wang, Dongsheng; Fu, Binqing; Zhou, Yonggang; Zheng, Xiaohu; Yang, Yun; Li, Xiuyong; Zhang, Xiaohua; Pan, Aijun; Wei, Haiming
Subjects: Medicine, Pharmacy >> Clinical Medicine

Background: In December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in Wuhan, China, which spread rapidly and has become a world-wide public health challenge. We aimed to assess the efficacy of tocilizumab in severe patients with Corona Virus Disease-19 (COVID-19) and seek a new therapeutic strategy. Methods: The patients diagnosed as severe or critical COVID-19 in The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital) and Anhui Fuyang Second People’s Hospital were given tocilizumab in addition to routine therapy between February 5 and February 14, 2020. The changes of clinical manifestations, CT scan image, and laboratory examinations were retrospectively analyzed. Findings: Within a few days, the fever returned to normal and all other symptoms improved remarkably. Fifteen of the 20 patients (75.0%) had lowered their oxygen intake and one patient need no oxygen therapy. CT scans manifested that the lung lesion opacity absorbed in 19 patients (90.5%). The percentage of lymphocytes in peripheral blood, which decreased in 85.0% patients (17/20) before treatment (mean, 15.52 ± 8.89%), returned to normal in 52.6% patients (10/19) on the fifth day after treatment. Abnormally elevated C-reactive protein decreased significantly in 84.2% patients (16/19). No obvious adverse reactions were observed. Nineteen patients (90.5%) have been discharged on average 13.5 days after the treatment with tocilizumab and the rest are recovering well. Interpretation: Tocilizumab is an effective treatment in severe patients of COVID-19, which provided a new therapeutic strategy for this fatal infectious disease.

submitted time 2020-03-05 Hits137970Downloads45675 Comment 0

3. chinaXiv:202002.00078 [pdf]

Confirmed asymptomatic carrier of SARS-CoV-2

Luo, Sihui; Liu, Wei; Liu, Zhenjun; Zheng, Xueying; Ling, Ping; Ding, Yu; Hong, Changxing; Liu, Zhirong; Liu, Jian; Weng, Jianping
Subjects: Medicine, Pharmacy >> Clinical Medicine

Here we reported a case of asymptomatic carrier of SARS-CoV-2 infection. A 50-year old woman, lived with her husband in Anqing(Anhui, China) with no significant past medical history, travel history to Wuhan or adjacent area, or exposure to wild animals. She took throat swab test for SARS-CoV-2 nucleic acid due to her husband’s close contact with patients who had SARS-CoV-2 infection. Her results were confirmed positive on February 6, 2020. But she did not report elevation of temperature measurement, nor respiratory or gastrointestinal symptoms and her chest CT scan showed no significant abnormalities. She was hospitalized on February 6 and treated with antiviral agents. During her hospitalization, apart from a mild elevation of liver enzymes after 10-day treatment of lopinavir/ritonavir, she was asymptomatic, with her blood cell count, live and renal function largely normal. Her subcutaneous oxygen saturation stayed above 97%. Chest CT scan was repeated on February 11 and 20, and both were negative for signs of viral pneumonia. Notably, a second set of throat swabs and anal swabs were sent to test for SARS-CoV-2 on February 19, and the results were still confirmed positive. This is a confirmed case of asymptomatic carrier of SARS-CoV-2 infection. Her persistent positive findings in both throat and anal swabs suggested the possibility of healthy carrier of the virus, which adds to the difficulty in preventing transmission of the disease.

submitted time 2020-02-28 Hits20446Downloads2300 Comment 0

4. chinaXiv:202002.00082 [pdf]

ACE2 shedding and furin abundance in target organs may influence the efficiency of SARS-CoV-2 entry

Yuanchen Ma; Yinong Huang; Tao Wang; Andy Peng Xiang; Weijun Huang
Subjects: Medicine, Pharmacy >> Preclinical Medicine

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recently identified lineage B coronavirus, causing rapid worldwide outbreak of Corona Virus Disease 2019 (COVID-19). Despite genetically closed to SARS-CoV, SARS-CoV-2 seems to possess enhanced infectivity and subtle different clinical features, which may hamper the early screening of suspected patients as well as the control of virus transmission. Unfortunately, there are few tools to predict the potential target organ damage and possible clinical manifestations caused by such novel coronavirus. To solve this problem, we investigate the potential host cell entry mechanisms of SARS-CoV-2 through bioinformatics. Using the online single-cell sequence datasets, we analyze the expression of major receptor in host cells that mediates the virus entry, including angiotensin converting enzyme 2 (ACE2), and its co-expressed membrane endopeptidases. The results indicated the differential expression of ADAM10 and ADAM17 might contribute to the ACE2 shedding and affect the membrane ACE2 abundance. We further confirm a putative furin-cleavage site reported recently in the spike protein of SARS-CoV-2, which may facilitate the virus-cell fusion. Based on these findings, we develop a novel approach that comprehensively analyzed the virus receptor expression, ACE2 shedding, membrane fusion activity, virus uptake and virus replication to evaluate the infectivity of SARS-CoV-2 to different human organs. Our results indicate that, in addition to airway epithelia, cardiac tissue and enteric canals are susceptible to SARS-CoV-2 as well.

submitted time 2020-02-27 Hits38535Downloads4012 Comment 0

5. chinaXiv:202002.00065 [pdf]

Potential of Arbidol for Post-exposure Prophylaxis of COVID-19 Transmission

Jinnong,Zhang; Wenjing,Wang; Bo,Peng; Wei,Peng; Yisheng,Zhang; Yaling,Wang; Yan,Wan; Jiang,Chang; Ling,Mao; Xiaoping,Miao; Yifan,Zhou; Yanan,Li; Yu,Hu; Bo,Hu
Subjects: Medicine, Pharmacy >> Clinical Medicine

Background: The efficient transmission of Severe Acute Respiratory Syndrome-2 Coronavirus (SARS-CoV-2) from patients to healthcare workers or family members has been a worrisome and prominent feature of the ongoing outbreak. On the basis of clinical practice and in-vitro studies, we postulated that post-exposure prophylaxis (PEP) using Arbidol is associated with decreased infection among individuals exposed to confirmed cases of COVID-19 infection. Methods: We conducted a retrospective case-control study on family members and health care workers who were exposed to patients confirmed to have SARS-CoV-2 infection by real-time RT-PCR and Chest CT from January 1 to January 16, 2020. We collected demographic information, work location of exposure, post-exposure prophylaxis information, and symptoms, if any, 24 days after exposure. The relation between post-exposure prophylaxis and infection in household contacts and healthcare workers were respectively analyzed. Results: 27 families and 124 health care workers had evidence of close exposure to patients with confirmed COVID-19. There were no differences in age, profession and sex distribution in the two groups with different post-exposure prophylaxis, table 1. Logistic regression based on the data of the family members and health care workers with Arbidol or Oseltamivir prophylaxis showed that Arbidol PEP was a strong protective factor against the development of COVID-19 (Odds ratio 0·011 , 95% CI 0·001-0·125, P=0·0003 for family members and Odds ratio 0·049, 95%CI 0·003-0·717), P= 0·0276 for health care workers). On the contrary, Oseltamivir was associated with an increase in COVID-19 infection (Odds ratio 20·446, 95% CI 1·407-297·143, P= 0·0271). Conclusions: Our findings suggest Arbidol could reduce the infection risk of the novel coronavirus in hospital and family settings. This treatment should be promoted for PEP use and should be the subject of further investigation.

submitted time 2020-02-26 Hits28118Downloads3001 Comment 0

6. chinaXiv:202002.00075 [pdf]

2019年新型冠状病毒导致的致命肺渗漏的病理生理学机制和防治策略

Chen, Sifeng
Subjects: Medicine, Pharmacy >> Preclinical Medicine

自2019年12月爆发以来,2019年新型冠状病毒已在全球造成2596人死亡,并且有超过11,000名患者仍处于严重状况。该病毒和由该病毒引起的医疗状况被命名为SARS-CoV-2和COVID-19。虽然已经广泛应用了抗病毒、对症和功能支持性疗法,每天仍有100多名患者死于该病毒感染。COVID-19最常见的致命并发症是急性呼吸窘迫综合征(ARDS)。SARS-CoV-2在世界范围内的大流行可能仍然存在。其它病毒感染引起的肺炎亦可导致ARDS,出现类似的危重情形,这些病毒包括如非典型的急性呼吸系统综合症(SARS)、中东呼吸综合征(MERS)和流感病毒引起的肺炎。因此,制定更有效的降低病毒所致的ARDS死亡率的策略,不但是当前抗新冠疫情的迫切需要,也是全球范围内降低病毒性肺炎死亡率的长期需要。ARDS曾被称为湿肺,血管泄漏导致的肺水肿是其最重要的病理特征之一,重型COVID-19的临床表现和胸部计算机断层扫描图像特征(白肺)符合ARDS。确定水肿液从何处及如何渗漏到肺部,是制定基于机制的预防和阻止水从肺毛细管向肺间质渗漏的策略,降低湿肺死亡率的关键。对于轻度和中度病例,非类固醇消炎药,如用于风湿性关节炎的药物,可能有助于防止和减少这种漏水。免疫抑制剂(如西罗莫司和巨蜥)可能使病毒感染、免疫反应和非免疫炎症造成的损伤高峰时间错开,从而降低肺漏水程度,防止危及生命情况出现。使用清火中草药可能也有抗炎用。对于严重病例,血液透析可能是消除大多数炎症介质和细胞毒性物质的有效策略。

submitted time 2020-02-25 Hits13242Downloads1176 Comment 0

7. chinaXiv:202002.00062 [pdf]

Furin, a potential therapeutic target for COVID-19

Hua Li; Canrong Wu; Yueying Yang; Yang Liu; Peng Zhang; Yali Wang; Qiqi Wang; Yang Xu; Mingxue Li; Mengzhu Zheng; Lixia Chen
Subjects: Medicine, Pharmacy >> Pharmacology

A novel coronavirus (SARS-CoV-2) infectious disease has broken out in Wuhan, Hubei Province since December 2019, and spread rapidly from Wuhan to other areas, which has been listed as an international concerning public health emergency. We compared the Spike proteins from four sources, SARS-CoV-2, SARS-CoV, MERS-CoV and Bat-CoVRaTG13, and found that the SARS-CoV-2 virus sequence had redundant PRRA sequences. Through a series of analyses, we propose the reason why SARS-CoV-2is more infectious than other coronaviruses. And through structure based virtual ligand screening, we foundpotentialfurin inhibitors, which might be used in the treatment of new coronary pneumonia.

submitted time 2020-02-23 Hits125812Downloads17263 Comment 0

8. chinaXiv:202002.00033 [pdf]

Decoding evolution and transmissions of novel pneumonia coronavirus using the whole genomic data

Yu, Wen-Bin; Tang, Guang-Da; Zhang, Li; Corlett, Richard T.
Subjects: Biology >> Virology
Subjects: Biology >> Genetics

Background. The outbreak of COVID-19 started in mid-December 2019 in Wuhan, Central China. Up to February 18, 2020, SARS-CoV-2 has infected more than 70,000 people in China, and another 25 countries across five continents. In this study, we used 93 complete genomes of SARS-CoV-2 from the GISAID EpiFluTM database to decode the evolution and human-to-human transmissions of SARS-CoV-2 in the recent two months. Methods. Alignment of coding-regions was conducted haplotype analyses using DnaSP. Substitution sites were analyzed in codon. Evolutionary analysis of haplotypes used NETWORK. Population size changes were estimated using both DnaSP and Arlequin. Expansion date of population size was calculated based on the expansion parameter tau (τ) using the formula t=τ/2u. Findings. Eight coding-regions have 120 substitution sites, including 79 non-synonymous and 40 synonymous substitutions. Forty-two non-synonymous substitutions changed the biochemical property of amino acids. No evident combination was found. Fifty-eight haplotypes were classified as five groups, and 31 haplotypes were found in samples from both China and other countries, respectively. The rooted network suggested H13 and H35 to be ancestral haplotypes, and H1 (and its descendent haplotypes including all samples from the Hua Nan market) was derived H3 haplotype. Population size of SARS-CoV-2 were estimated to have a recent expansion on 6 January 2020, and an early expansion on 8 December 2019. Interpretation. Genomic variations of SARS-CoV-2 are still low in comparisons with published genomes of SARS-CoV and MERS-CoV. Phyloepidemiologic analyses indicated the SARS-CoV-2 source at the Hua Nan market should be imported from other places. The crowded market boosted SARS-CoV-2 rapid circulations in the market and spread it to the whole city in early December 2019. Furthermore, phyloepidemiologic approaches have recovered specific direction of human-to-human transmissions, and the import sources of international infectious cases.

submitted time 2020-02-21 Hits284596Downloads72231 Comment 0

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