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Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 77,926 bioRxiv papers from 337,673 authors.

Most downloaded bioRxiv papers, since beginning of last month

76,070 results found. For more information, click each entry to expand.

21: The first-in-class peptide binder to the SARS-CoV-2 spike protein
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Posted to bioRxiv 20 Mar 2020

The first-in-class peptide binder to the SARS-CoV-2 spike protein
6,258 downloads bioengineering

G. Zhang, S. Pomplun, A. R. Loftis, A. Loas, B. L. Pentelute

Coronavirus disease 19 (COVID-19) is an emerging global health crisis. With over 200,000 confirmed cases to date, this pandemic continues to expand, spurring research to discover vaccines and therapies. SARS-CoV-2 is the novel coronavirus responsible for this disease. It initiates entry into human cells by binding to angiotensin-converting enzyme 2 (ACE2) via the receptor binding domain (RBD) of its spike protein (S). Disrupting the SARS-CoV-2-RBD binding to ACE2 with designer drugs has the potential to inhibit the virus from entering human cells, presenting a new modality for therapeutic intervention. Peptide-based binders are an attractive solution to inhibit the RBD-ACE2 interaction by adequately covering the extended protein contact interface. Using molecular dynamics simulations based on the recently solved ACE2 and SARS-CoV-2-RBD co-crystal structure, we observed that the ACE2 peptidase domain (PD) α1 helix is important for binding SARS-CoV-2-RBD. Using automated fast-flow peptide synthesis, we chemically synthesized a 23-mer peptide fragment of the ACE2 PD α1 helix composed entirely of proteinogenic amino acids. Chemical synthesis of this human derived sequence was complete in 1.5 hours and after work up and isolation >20 milligrams of pure material was obtained. Bio-layer interferometry revealed that this peptide specifically associates with the SARS-CoV-2-RBD with low nanomolar affinity. This peptide binder to SARS-CoV-2-RBD provides new avenues for COVID-19 treatment and diagnostic modalities by blocking the SARS-CoV-2 spike protein interaction with ACE2 and thus precluding virus entry into human cells.

22: Efficient inactivation of SARS-CoV-2 by WHO-recommended hand rub formulations and alcohols
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Posted to bioRxiv 17 Mar 2020

Efficient inactivation of SARS-CoV-2 by WHO-recommended hand rub formulations and alcohols
5,946 downloads microbiology

Annika Kratzel, Daniel Todt, Philip V’kovski, Silvio Steiner, Mitra L Gultom, Tran Thi Nhu Thao, Nadine Ebert, Melle Holwerda, Jörg Steinmann, Daniela Niemeyer, Ronald Dijkman, Günter Kampf, Christian Drosten, Eike Steinmann, Volker Thiel, Stephanie Pfaender

The recent emergence of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing COVID-19 is a major burden for health care systems worldwide. It is important to address if the current infection control instructions based on active ingredients are sufficient. We therefore determined the virucidal activity of two alcohol-based hand rub solutions for hand disinfection recommended by the World Health Organization (WHO), as well as commercially available alcohols. Efficient SARS-CoV-2 inactivation was demonstrated for all tested alcohol-based disinfectants. These findings show the successful inactivation of SARS-CoV-2 for the first time and provide confidence in its use for the control of COVID-19.

23: SARS-CoV-2 launches a unique transcriptional signature from in vitro, ex vivo, and in vivo systems
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Posted to bioRxiv 24 Mar 2020

SARS-CoV-2 launches a unique transcriptional signature from in vitro, ex vivo, and in vivo systems
5,677 downloads microbiology

Daniel Blanco-Melo, Benjamin E. Nilsson-Payant, Wen-Chun Liu, Rasmus Møller, Maryline Panis, David Sachs, Randy A. Albrecht, Benjamin R. tenOever

One of the greatest threats to humanity is the emergence of a pandemic virus. Among those with the greatest potential for such an event include influenza viruses and coronaviruses. In the last century alone, we have observed four major influenza A virus pandemics as well as the emergence of three highly pathogenic coronaviruses including SARS-CoV-2, the causative agent of the ongoing COVID-19 pandemic. As no effective antiviral treatments or vaccines are presently available against SARS-CoV-2, it is important to understand the host response to this virus as this may guide the efforts in development towards novel therapeutics. Here, we offer the first in-depth characterization of the host transcriptional response to SARS-CoV-2 and other respiratory infections through in vitro, ex vivo, and in vivo model systems. Our data demonstrate the each virus elicits both core antiviral components as well as unique transcriptional footprints. Compared to the response to influenza A virus and respiratory syncytial virus, SARS-CoV-2 elicits a muted response that lacks robust induction of a subset of cytokines including the Type I and Type III interferons as well as a numerous chemokines. Taken together, these data suggest that the unique transcriptional signature of this virus may be responsible for the development of COVID-19.

24: Screening of FDA-approved drugs using a MERS-CoV clinical isolate from South Korea identifies potential therapeutic options for COVID-19
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Posted to bioRxiv 02 Mar 2020

Screening of FDA-approved drugs using a MERS-CoV clinical isolate from South Korea identifies potential therapeutic options for COVID-19
5,000 downloads microbiology

Meehyun Ko, So Young Chang, Soo Young Byun, Inhee Choi, Anne-Laure Pham Hung d’Alexandry d’Orengiani, David Shum, Ji-Young Min, Marc P. Windisch

In 2015, the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) reached the Republic of Korea through nosocomial transmission and was the largest epidemic outside of the Arabian Peninsula. To date, despite various strategies to identify CoV interventions, only limited therapeutic options are available. To address these unmet medical needs, we used a South Korean MERS-CoV clinical isolate and screened 5,406 compounds, including United States Food and Drug Administration (FDA)-approved drugs and bioactive molecules, for their activity against the isolate. The primary assay confirmed 221 hits by dose-response curve analysis and identified 54 hits with a therapeutic index (TI) greater than 6. Time-of-addition studies with 12 FDA-approved drugs demonstrated that 8 and 4 therapeutics act on the early and late stages of the viral life cycle, respectively. Among the drugs were e.g., three cardiotonic agents (ouabain, digitoxin, digoxin) with a TI greater than 100, an anti-malaria drug (atovaquone; TI >34), an inhalable corticosteroid (ciclesonide; TI >6), etc. Together, our results identify potential therapeutic options for treating MERS-CoV infections and could provide a basis for agents against a wider range of coronavirus-related illnesses, including the currently emerging Coronavirus Disease 2019 (COVID-19) outbreak.

25: The Pathogenicity of SARS-CoV-2 in hACE2 Transgenic Mice
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Posted to bioRxiv 11 Feb 2020

The Pathogenicity of SARS-CoV-2 in hACE2 Transgenic Mice
4,705 downloads microbiology

Linlin Bao, Wei Deng, Baoying Huang, Hong Gao, Jiangning Liu, Lili Ren, Qiang Wei, Pin Yu, Yanfeng Xu, Feifei Qi, Yajin Qu, Fengdi Li, Qi Lv, Wenling Wang, Jing Xue, Shuran Gong, Mingya Liu, Guanpeng Wang, Shunyi Wang, Zhiqi Song, Linna Zhao, Peipei Liu, Li Zhao, Fei Ye, Huijuan Wang, Weimin Zhou, Na Zhu, Wei Zhen, Haisheng Yu, Xiaojuan Zhang, Li Guo, Lan Chen, Conghui Wang, Ying Wang, Xinming Wang, Yan Xiao, Qiangming Sun, Hongqi Liu, Fanli Zhu, Chunxia Ma, Lingmei Yan, Mengli Yang, Jun Han, Wenbo Xu, Wenjie Tan, Xiaozhong Peng, Qi Jin, Guizhen Wu, Chuan Qin

Severe acute respiratory syndrome CoV-2 (SARS-CoV-2) caused the Corona Virus Disease 2019 (COVID-19) cases in China has become a public health emergency of international concern (PHEIC). Based on angiotensin converting enzyme 2 (ACE2) as cell entry receptor of SARS-CoV, we used the hACE2 transgenic mice infected with SARS-CoV-2 to study the pathogenicity of the virus. Weight loss and virus replication in lung were observed in hACE2 mice infected with SARS-CoV-2. The typical histopathology was interstitial pneumonia with infiltration of significant lymphocytes and monocytes in alveolar interstitium, and accumulation of macrophages in alveolar cavities. Viral antigens were observed in the bronchial epithelial cells, alveolar macrophages and alveolar epithelia. The phenomenon was not found in wild type mice with SARS-CoV-2 infection. The pathogenicity of SARS-CoV-2 in hACE2 mice was clarified and the Koch’s postulates were fulfilled as well, and the mouse model may facilitate the development of therapeutics and vaccines against SARS-CoV-2.

26: Viral Architecture of SARS-CoV-2 with Post-Fusion Spike Revealed by Cryo-EM
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Posted to bioRxiv 05 Mar 2020

Viral Architecture of SARS-CoV-2 with Post-Fusion Spike Revealed by Cryo-EM
4,644 downloads microbiology

Chuang Liu, Yang Yang, Yuanzhu Gao, Chenguang Shen, Bin Ju, Congcong Liu, Xian Tang, Jinli Wei, Xiaomin Ma, Weilong Liu, Shuman Xu, Yingxia Liu, Jing Yuan, Jing Wu, Zheng Liu, Zheng Zhang, Peiyi Wang, Lei Liu

Since December 2019, the outbreak of Coronavirus Disease 2019 (COVID-19) spread from Wuhan, China to the world, it has caused more than 87,000 diagnosed cases and more than 3,000 deaths globally. To fight against COVID-19, we carried out research for the near native SARS-CoV-2 and report here our preliminary results obtained. The pathogen of the COVID-19, the native SARS-CoV-2, was isolated, amplified and purified in a BSL-3 laboratory. The whole viral architecture of SARS-CoV-2 was examined by transmission electron microscopy (both negative staining and cryo-EM). We observed that the virion particles are roughly spherical or moderately pleiomorphic. Spikes have nail-like shape towards outside with a long body embedded in the envelope. The morphology of virion observed in our result indicates that the S protein of SARS-CoV-2 is in post-fusion state, with S1 disassociated. This state revealed by cryo-EM first time could provide an important information for the identification and relevant clinical research of this new coronavirus.

27: Isolation and Characterization of 2019-nCoV-like Coronavirus from Malayan Pangolins
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Posted to bioRxiv 20 Feb 2020

Isolation and Characterization of 2019-nCoV-like Coronavirus from Malayan Pangolins
4,551 downloads microbiology

Kangpeng Xiao, Junqiong Zhai, Yaoyu Feng, Niu Zhou, Xu Zhang, Jie-Jian Zou, Na Li, Yaqiong Guo, Xiaobing Li, Xuejuan Shen, Zhipeng Zhang, Fanfan Shu, Wanyi Huang, Li, Ziding Zhang, Rui-Ai Chen, Ya-Jiang Wu, Shi-Ming Peng, Mian Huang, Wei-Jun Xie, Qin-Hui Cai, Fang-Hui Hou, Yahong Liu, Wu Chen, Lihua Xiao, Yongyi Shen

The outbreak of 2019-nCoV in the central Chinese city of Wuhan at the end of 2019 poses unprecedent public health challenges to both China and the rest world. The new coronavirus shares high sequence identity to SARS-CoV and a newly identified bat coronavirus. While bats may be the reservoir host for various coronaviruses, whether 2019-nCoV has other hosts is still ambiguous. In this study, one coronavirus isolated from Malayan pangolins showed 100%, 98.2%, 96.7% and 90.4% amino acid identity with 2019-nCoV in the E, M, N and S genes, respectively. In particular, the receptor-binding domain of the S protein of the Pangolin-CoV is virtually identical to that of 2019-nCoV, with one amino acid difference. Comparison of available genomes suggests 2019-nCoV might have originated from the recombination of a Pangolin-CoV-like virus with a Bat-CoV-RaTG13-like virus. Infected pangolins showed clinical signs and histopathological changes, and the circulating antibodies reacted with the S protein of 2019-nCoV. The isolation of a coronavirus that is highly related to 2019-nCoV in the pangolins suggests that these animals have the potential to act as the intermediate host of 2019-nCoV. The newly identified coronavirus in the most-trafficked mammal could represent a continuous threat to public health if wildlife trade is not effectively controlled.

28: The architecture of SARS-CoV-2 transcriptome
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Posted to bioRxiv 14 Mar 2020

The architecture of SARS-CoV-2 transcriptome
4,485 downloads genomics

Dongwan Kim, Joo-Yeon Lee, Jeong-Sun Yang, Jun Won Kim, V. Narry Kim, Hyeshik Chang

SARS-CoV-2 is a betacoronavirus that is responsible for the COVID-19 pandemic. The genome of SARS-CoV-2 was reported recently, but its transcriptomic architecture is unknown. Utilizing two complementary sequencing techniques, we here present a high-resolution map of the SARS-CoV-2 transcriptome and epitranscriptome. DNA nanoball sequencing shows that the transcriptome is highly complex owing to numerous recombination events, both canonical and noncanonical. In addition to the genomic RNA and subgenomic RNAs common in all coronaviruses, SARS-CoV-2 produces a large number of transcripts encoding unknown ORFs with fusion, deletion, and/or frameshift. Using nanopore direct RNA sequencing, we further find at least 41 RNA modification sites on viral transcripts, with the most frequent motif being AAGAA. Modified RNAs have shorter poly(A) tails than unmodified RNAs, suggesting a link between the internal modification and the 3′ tail. Functional investigation of the unknown ORFs and RNA modifications discovered in this study will open new directions to our understanding of the life cycle and pathogenicity of SARS-CoV-2. Highlights

29: Cryo-EM Structure of the 2019-nCoV Spike in the Prefusion Conformation
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Posted to bioRxiv 15 Feb 2020

Cryo-EM Structure of the 2019-nCoV Spike in the Prefusion Conformation
4,445 downloads microbiology

Daniel Wrapp, Nianshuang Wang, Kizzmekia S. Corbett, Jory A Goldsmith, Ching-Lin Hsieh, Olubukola Abiona, Barney Graham, Jason S. McLellan

The outbreak of a novel betacoronavirus (2019-nCov) represents a pandemic threat that has been declared a public health emergency of international concern. The CoV spike (S) glycoprotein is a key target for urgently needed vaccines, therapeutic antibodies, and diagnostics. To facilitate medical countermeasure (MCM) development we determined a 3.5 Å-resolution cryo-EM structure of the 2019-nCoV S trimer in the prefusion conformation. The predominant state of the trimer has one of the three receptor-binding domains (RBDs) rotated up in a receptor-accessible conformation. We also show biophysical and structural evidence that the 2019-nCoV S binds ACE2 with higher affinity than SARS-CoV S. Additionally we tested several published SARS-CoV RBD-specific monoclonal antibodies and found that they do not have appreciable binding to nCoV-2019 S, suggesting antibody cross-reactivity may be limited between the two virus RBDs. The cryo-EM structure of 2019-nCoV S should enable rapid development and evaluation of MCMs to address the ongoing public health crisis.

30: Development of CRISPR as a prophylactic strategy to combat novel coronavirus and influenza
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Posted to bioRxiv 14 Mar 2020

Development of CRISPR as a prophylactic strategy to combat novel coronavirus and influenza
4,391 downloads bioengineering

Timothy R. Abbott, Girija Dhamdhere, Yanxia Liu, Xueqiu Lin, Laine Goudy, Leiping Zeng, Augustine Chemparathy, Stephen Chmura, Nicholas S Heaton, Robert Debs, Tara Pande, Drew Endy, Marie La Russa, David B Lewis, Lei S. Qi

The outbreak of the coronavirus disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), has infected more than 100,000 people worldwide with over 3,000 deaths since December 2019. There is no cure for COVID-19 and the vaccine development is estimated to require 12-18 months. Here we demonstrate a CRISPR-Cas13-based strategy, PAC-MAN (Prophylactic Antiviral CRISPR in huMAN cells), for viral inhibition that can effectively degrade SARS-CoV-2 sequences and live influenza A virus (IAV) genome in human lung epithelial cells. We designed and screened a group of CRISPR RNAs (crRNAs) targeting conserved viral regions and identified functional crRNAs for cleaving SARS-CoV-2. The approach is effective in reducing respiratory cell viral replication for H1N1 IAV. Our bioinformatic analysis showed a group of only six crRNAs can target more than 90% of all coronaviruses. The PAC-MAN approach is potentially a rapidly implementable pan-coronavirus strategy to deal with emerging pandemic strains.

31: An integrated brain-machine interface platform with thousands of channels
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Posted to bioRxiv 17 Jul 2019

An integrated brain-machine interface platform with thousands of channels
4,288 downloads neuroscience

Elon Musk, Neuralink

Brain-machine interfaces (BMIs) hold promise for the restoration of sensory and motor function and the treatment of neurological disorders, but clinical BMIs have not yet been widely adopted, in part because modest channel counts have limited their potential. In this white paper, we describe Neuralink’s first steps toward a scalable high-bandwidth BMI system. We have built arrays of small and flexible electrode “threads”, with as many as 3,072 electrodes per array distributed across 96 threads. We have also built a neurosurgical robot capable of inserting six threads (192 electrodes) per minute. Each thread can be individually inserted into the brain with micron precision for avoidance of surface vasculature and targeting specific brain regions. The electrode array is packaged into a small implantable device that contains custom chips for low-power on-board amplification and digitization: the package for 3,072 channels occupies less than (23 × 18.5 × 2) mm3. A single USB-C cable provides full-bandwidth data streaming from the device, recording from all channels simultaneously. This system has achieved a spiking yield of up to 70% in chronically implanted electrodes. Neuralink’s approach to BMI has unprecedented packaging density and scalability in a clinically relevant package.

32: Identification of 2019-nCoV related coronaviruses in Malayan pangolins in southern China
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Posted to bioRxiv 18 Feb 2020

Identification of 2019-nCoV related coronaviruses in Malayan pangolins in southern China
4,150 downloads microbiology

Tommy Tsan-Yuk Lam, Marcus Ho-Hin Shum, Hua-Chen Zhu, Yi-Gang Tong, Xue-Bing Ni, Yun-Shi Liao, Wei Wei, William Yiu-Man Cheung, Wen-Juan Li, Lian-Feng Li, Gabriel M. Leung, Edward C. Holmes, Yan-Ling Hu, Yi Guan

The ongoing outbreak of viral pneumonia in China and beyond is associated with a novel coronavirus, provisionally termed 2019-nCoV. This outbreak has been tentatively associated with a seafood market in Wuhan, China, where the sale of wild animals may be the source of zoonotic infection. Although bats are likely reservoir hosts for 2019-nCoV, the identity of any intermediate host facilitating transfer to humans is unknown. Here, we report the identification of 2019-nCoV related coronaviruses in pangolins (Manis javanica) seized in anti-smuggling operations in southern China. Metagenomic sequencing identified pangolin associated CoVs that belong to two sub-lineages of 2019-nCoV related coronaviruses, including one very closely related to 2019-nCoV in the receptor-binding domain. The discovery of multiple lineages of pangolin coronavirus and their similarity to 2019-nCoV suggests that pangolins should be considered as possible intermediate hosts for this novel human virus and should be removed from wet markets to prevent zoonotic transmission.

33: Comparative analysis of primer-probe sets for the laboratory confirmation of SARS-CoV-2
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Posted to bioRxiv 27 Feb 2020

Comparative analysis of primer-probe sets for the laboratory confirmation of SARS-CoV-2
4,081 downloads microbiology

Yu Jin Jung, Gun-Soo Park, Jun Hye Moon, Keunbon Ku, Seung-Hwa Beak, Seil Kim, Edmond Changkyun Park, Daeui Park, Jong-Hwan Lee, Cheol Woo Byeon, Joong Jin Lee, Jin-Soo Maeng, Seong Jun Kim, Seung Il Kim, Bum-Tae Kim, Min Jun Lee, Hong Gi Kim

Coronavirus disease 2019 (COVID-19) is newly emerging human infectious diseases, which is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2, also previously known as 2019-nCoV). Within two months of the outbreak, more than 80,000 cases of COVID-19 have been confirmed worldwide. Since the human to human transmission occurred easily and the human infection is rapidly increasing, the sensitive and early diagnosis is essential to prevent the global outbreak. Recently, World Health Organization (WHO) announced various primer and probe sets for SARS-CoV-2 previously developed in China, Germany, Hong Kong, Japan, Thailand, and USA. In this study, we compared the ability to detect SARS-CoV-2 RNA among the seven primer-probe sets for N gene and the three primer-probe sets for Orf1 gene. The result of the comparative analysis represented that the 2019-nCoV\_N2, N3 of USA and the ORF1ab of China are the most sensitive primer-probe sets for N and Orf1 genes, respectively. Therefore, the appropriate combination from ORF1ab (China), 2019-nCoV\_N2, N3 (USA), and NIID\_2019-nCOV\_N (Japan) sets should be selected for the sensitive and reliable laboratory confirmation of SARS-CoV-2.

34: Isolation and characterization of SARS-CoV-2 from the first US COVID-19 patient
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Posted to bioRxiv 03 Mar 2020

Isolation and characterization of SARS-CoV-2 from the first US COVID-19 patient
4,022 downloads microbiology

Jennifer Harcourt, Azaibi Tamin, Xiaoyan Lu, Shifaq Kamili, Senthil Kumar Sakthivel, Janna Murray, Krista Queen, Ying Tao, Clinton R. Paden, Jing Zhang, Yan Li, Anna Uehara, Haibin Wang, Cynthia Goldsmith, Hannah A. Bullock, Lijuan Wang, Brett Whitaker, Brian Lynch, Rashi Gautam, Craig Schindewolf, Kumari G. Lokugamage, Dionna Scharton, Jessica A. Plante, Divya Mirchandani, Steven G. Widen, Krishna Narayanan, Shinji Makino, Thomas G. Ksiazek, Kenneth S Plante, Scott C. Weaver, Stephen Lindstrom, Suxiang Tong, Vineet D. Menachery, Natalie J. Thornburg

The etiologic agent of the outbreak of pneumonia in Wuhan China was identified as severe acute respiratory syndrome associated coronavirus 2 (SARS-CoV-2) in January, 2020. The first US patient was diagnosed by the State of Washington and the US Centers for Disease Control and Prevention on January 20, 2020. We isolated virus from nasopharyngeal and oropharyngeal specimens, and characterized the viral sequence, replication properties, and cell culture tropism. We found that the virus replicates to high titer in Vero-CCL81 cells and Vero E6 cells in the absence of trypsin. We also deposited the virus into two virus repositories, making it broadly available to the public health and research communities. We hope that open access to this important reagent will expedite development of medical countermeasures. Article Summary Scientists have isolated virus from the first US COVID-19 patient. The isolation and reagents described here will serve as the US reference strain used in research, drug discovery and vaccine testing.

35: The inhaled corticosteroid ciclesonide blocks coronavirus RNA replication by targeting viral NSP15
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Posted to bioRxiv 12 Mar 2020

The inhaled corticosteroid ciclesonide blocks coronavirus RNA replication by targeting viral NSP15
3,970 downloads microbiology

Shutoku Matsuyama, Miyuki Kawase, Naganori Nao, Kazuya Shirato, Makoto Ujike, Wataru Kamitani, Masayuki Shimojima, Shuetsu Fukushi

Steroid compounds, which are expected to have dual functions in blocking host inflammation and MERS-CoV replication, were screened from a chemical library. Within this library, ciclesonide, an inhaled corticosteroid, suppressed human coronavirus replication in cultured cells, but did not suppress replication of respiratory syncytial virus or influenza virus. The effective concentration of ciclesonide to block SARS-CoV-2 (the cause of COVID-19) replication (EC90) was 6.3 μM. After the eleventh consecutive MERS-CoV passage in the presence of ciclesonide, a resistant mutation was generated, which resulted in an amino acid substitution (A25V) in nonstructural protein (NSP) 15, as identified using reverse genetics. A recombinant virus with the mutation was also resistant to ciclesonide suppression of viral replication. These observations suggest that the effect of ciclesonide was specific to coronavirus, suggesting this is a candidate drug for treatment of patients suffering MERS or COVID-19.

36: LY6E impairs coronavirus fusion and confers immune control of viral disease
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Posted to bioRxiv 07 Mar 2020

LY6E impairs coronavirus fusion and confers immune control of viral disease
3,965 downloads microbiology

Stephanie Pfaender, Katrina B Mar, Eleftherios Michailidis, Annika Kratzel, Dagny Hirt, Philip V’kovski, Wenchun Fan, Nadine Ebert, Hanspeter Stalder, Hannah Kleine-Weber, Markus Hoffmann, H. Heinrich Hoffmann, Mohsan Saeed, Ronald Dijkman, Eike Steinmann, Mary Wight-Carter, Natasha W Hanners, Stefan Pöhlmann, Tom Gallagher, Daniel Todt, Gert Zimmer, Charles M. Rice, John W. Schoggins, Volker Thiel

Zoonotic coronaviruses (CoVs) are significant threats to global health, as exemplified by the recent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Host immune responses to CoV are complex and regulated in part through antiviral interferons. However, the interferon-stimulated gene products that inhibit CoV are not well characterized. Here, we show that interferon-inducible lymphocyte antigen 6 complex, locus E (LY6E) potently restricts cellular infection by multiple CoVs, including SARS-CoV, SARS-CoV-2, and Middle East respiratory syndrome coronavirus (MERS-CoV). Mechanistic studies revealed that LY6E inhibits CoV entry into cells by interfering with spike protein-mediated membrane fusion. Importantly, mice lacking Ly6e in hematopoietic cells were highly susceptible to murine CoV infection. Exacerbated viral pathogenesis in Ly6e knockout mice was accompanied by loss of hepatic and splenic immune cells and reduction in global antiviral gene pathways. Accordingly, we found that Ly6e directly protects primary B cells and dendritic cells from murine CoV infection. Our results demonstrate that LY6E is a critical antiviral immune effector that controls CoV infection and pathogenesis. These findings advance our understanding of immune-mediated control of CoV in vitro and in vivo, knowledge that could help inform strategies to combat infection by emerging CoV.

37: SARS-CoV-2 sensitive to type I interferon pretreatment.
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Posted to bioRxiv 09 Mar 2020

SARS-CoV-2 sensitive to type I interferon pretreatment.
3,958 downloads microbiology

Kumari G. Lokugamage, Adam Hage, Craig Schindewolf, Ricardo Rajsbaum, Vineet D. Menachery

SARS-CoV-2, a novel coronavirus (CoV), has recently emerged causing an ongoing outbreak of viral pneumonia around the world. While genetically distinct from the original SARS-CoV, both group 2B coronaviruses share similar genome organization and origins to coronaviruses harbored in bats. Importantly, initial guidance has used insights from SARS-CoV infection to inform treatment and public health strategies. In this report, we evaluate SARS-CoV-2 relative to the original SARS-CoV. Our results indicate that while SARS-CoV-2 maintains similar viral replication kinetics to SARS-CoV in Vero cell, the novel coronavirus is much more sensitive to type I interferon pretreatment. We subsequently examined homology between SARS-CoV and SARS-CoV-2 in viral proteins shown to be interferon antagonist. The absence of open reading frame (ORF) 3b and significant changes to ORF6 suggest the two key IFN antagonists may not maintain equivalent function in SARS-CoV-2. Together, the results identify key differences in susceptibility to the IFN response between SARS-CoV and SARS-CoV-2 that could help inform disease progression, treatment options, and animal model development.

38: Full-genome evolutionary analysis of the novel corona virus (2019-nCoV) rejects the hypothesis of emergence as a result of a recent recombination event
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Posted to bioRxiv 27 Jan 2020

Full-genome evolutionary analysis of the novel corona virus (2019-nCoV) rejects the hypothesis of emergence as a result of a recent recombination event
3,871 downloads microbiology

D. Paraskevis, E.G. Kostaki, G. Magiorkinis, G. Panayiotakopoulos, S. Tsiodras

Background: A novel coronavirus (2019-nCoV) associated with human to human transmission and severe human infection has been recently reported from the city of Wuhan in China. Our objectives were to characterize the genetic relationships of the 2019-nCoV and to search for putative recombination within the subgenus of sarbecovirus. Methods: Putative recombination was investigated by RDP4 and Simplot v3.5.1 and discordant phylogenetic clustering in individual genomic fragments was confirmed by phylogenetic analysis using maximum likelihood and Bayesian methods. Results: Our analysis suggests that the 2019-nCoV although closely related to BatCoV RaTG13 sequence throughout the genome (sequence similarity 96.3%), shows discordant clustering with the Bat-SARS-like coronavirus sequences. Specifically, in the 5′-part spanning the first 11,498 nucleotides and the last 3′-part spanning 24,341-30,696 positions, 2019-nCoV and RaTG13 formed a single cluster with Bat-SARS-like coronavirus sequences, whereas in the middle region spanning the 3′-end of ORF1a, the ORF1b and almost half of the spike regions, 2019-nCoV and RaTG13 grouped in a separate distant lineage within the sarbecovirus branch. Conclusions: The levels of genetic similarity between the 2019-nCoV and RaTG13 suggest that the latter does not provide the exact variant that caused the outbreak in humans, but the hypothesis that 2019-nCoV has originated from bats is very likely. We show evidence that the novel coronavirus (2019-nCov) is not-mosaic consisting in almost half of its genome of a distinct lineage within the betacoronavirus. These genomic features and their potential association with virus characteristics and virulence in humans need further attention.

39: Time-varying transmission dynamics of Novel Coronavirus Pneumonia in China
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Posted to bioRxiv 26 Jan 2020

Time-varying transmission dynamics of Novel Coronavirus Pneumonia in China
3,588 downloads systems biology

Tao Liu, Jianxiong Hu, Jianpeng Xiao, Guanhao He, Min Kang, Zuhua Rong, Lifeng Lin, Haojie Zhong, Qiong Huang, Aiping Deng, Weilin Zeng, Xiaohua Tan, Siqing Zeng, Zhihua Zhu, Jiansen Li, Dexin Gong, Donghua Wan, Shaowei Chen, Lingchuan Guo, Yan Li, Limei Sun, Wenjia Liang, Tie Song, Jianfeng He, Wenjun Ma

Objectives: We aimed to estimate the basic and time-varying transmission dynamics of NCP across China, and compared them with SARS. Methods: Data on NCP cases by February 7, 2020 were collected from epidemiological investigations or official websites. Data on severe acute respiratory syndrome (SARS) cases in Guangdong Province, Beijing and HongKong during 2002-2003 were also obtained. We estimated the doubling time, basic reproduction number (R0) and time-varying reproduction number (Rt) of NCP and SARS. Measurements and main results: As of February 7, 2020, 34,598 NCP cases were identified in China, and daily confirmed cases decreased after February 4. The doubling time of NCP nationwide was 2.4 days which was shorter than that of SARS in Guangdong (14.3 days), Hong Kong (5.7 days) and Beijing (12.4 days). The R0 of NCP cases nationwide and in Wuhan were 4.5 and 4.4 respectively, which were higher than R0 of SARS in Guangdong(R0=2.3), Hongkong (R0=2.3), and Beijing (R0=2.6). The Rt for NCP continuously decreased especially after January 16 nationwide and in Wuhan. The R0 for secondary NCP cases in Guangdong was 0.6, and the Rt values were less than 1 during the epidemic. Conclusions: NCP may have a higher transmissibility than SARS, and the efforts of containing the outbreak are effective. However, the efforts are needed to persist in for reducing time-varying reproduction number below one.

40: Formulation, Evaluation and Antibacterial Efficiency of water-based herbal Hand Sanitizer Gel
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Posted to bioRxiv 22 Jul 2018

Formulation, Evaluation and Antibacterial Efficiency of water-based herbal Hand Sanitizer Gel
3,543 downloads microbiology

Shri Balakrishna Acharya, Saradindu Ghosh, Giriraj Yadav, Kavita Sharma, Sirsendu Ghosh, Sushil Joshi

Hands are the primary mode of transmission of microbes and infections. Hand-washing is critical in food production, food service and also important in a healthcare setting, homes and daycare preparations. The present research was aimed to evaluate the antibacterial efficacy of various herbal oils such as Cinnamon oil, Eucalyptus oil, menthol oil and lavender oil and found that cinnamon oil showed better antibacterial activity. Also, the research was carried out to formulate and evaluate the polyherbal Hand wash gel containing Azadirachta indica, Ocimum sanctum and Citrus limon extracts. The anti-microbial activity of the formulated herbal hand wash gel was tested against Escherichia coli, Staphylococcus aureus and Salmonella by spread plate techniques and the results obtained were compared with commercial antibacterial standards. Also, the efficiency was checked by using the hand wash gel on volunteers. The results from the present work suggest and support the incorporation and utilization of herbs in the formulations to give a better effect.

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