COVID-19 / SARS-CoV-2 preprints
List of important preprints dealing with the ongoing coronavirus outbreak. See http://covidpreprints.com for additional resources and timeline, and https://connect.biorxiv.org/relate/content/181 for full list of bioRxiv and medRxiv preprints on this topic
List by Dey Lab, Zhang-He GohPreprints:
Discovery of a novel coronavirus associated with the recent pneumonia outbreak in humans and its potential bat origin
https://www.biorxiv.org/content/10.1101/2020.01.22.914952v2
Reports the identification and characterization of (nCoV-2019). Full-length genome sequences were obtained from patients, and were found to share 79.5% sequence identify to SARS-CoV, and to be 96% identical at the whole genome level to a bat coronavirus. Study confirmed that virus uses the same cell entry receptor, ACE2, as SARS-CoV.
Pattern of early human-to-human transmission of Wuhan 2019-nCoV
https://www.biorxiv.org/content/10.1101/2020.01.23.917351v1
Reports stochastic simulations of early outbreak trajectories. Found that transmission characteristics were similar in magnitude to SARS-CoV and the 1918 pandemic influenza. Underlied importance of surveillance and early control.
Full-genome evolutionary analysis of the novel corona virus (2019-nCoV) rejects the hypothesis of emergence as a result of a recent recombination event
https://www.biorxiv.org/content/10.1101/2020.01.26.920249v1
The analysis suggests that the 2019-nCoV shows discordant clustering with the Bat-SARS-like coronavirus sequences. Almost half of the virus’ genome is of a distinct lineage within the betacoronavirus.
Beware of asymptomatic transmission: Study on 2019-nCoV prevention and control measures based on extended SEIR model
https://www.biorxiv.org/content/10.1101/2020.01.28.923169v1
Based on model studying the movement of people, this study is among first suggesting importance of testing, given role of assymptomatic transmission
Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody
https://www.biorxiv.org/content/10.1101/2020.01.28.923011v1
Study found that a SARS-CoV-specific human monoclonal antibody, CR3022, could bind potently with 2019-nCoV RBD, and proposes CR3022 as a potential candidate for therapeutics. The study emphasizes that various other antibodies that successfully neutralize SARS-CoV, fail to neutralize 2019-nCoV.
The incubation period of 2019-nCoV infections among travellers from Wuhan, China
https://www.medrxiv.org/content/10.1101/2020.01.27.20018986v2
Using the travel history of cases detected outside Wuhan, authors first estimated the mean incubation period to be 6.4 days, ranging from 2.1 to 11.1 days. They first suggested using these values for case definition.
Evolution and variation of 2019-novel coronavirus
https://www.biorxiv.org/content/10.1101/2020.01.30.926477v1
The study found a viral isolate different from other 2019-nCoVs, and suggests at least two different viral strains of 2019-nCoV are involved in the outbreak.
The novel coronavirus 2019 (2019-nCoV) uses the SARS-coronavirus receptor ACE2 and the cellular protease TMPRSS2 for entry into target cells
https://www.biorxiv.org/content/10.1101/2020.01.31.929042v1.full
SARS-CoV-2 enters cells via SARS-coronavirus receptor, ACE2, and cellular protease TMPRSS2. TMPRSS2 inhibitor and serum from convalescent SARS patient prevented entry of SARS-CoV-2. This highlights the similarities between SARS-CoV-2 and SARS-coronavirus infections and could identify a potential target for antiviral intervention.
The digestive system is a potential route of 2019-nCov infection: a bioinformatics analysis based on single-cell transcriptomes
https://www.biorxiv.org/content/10.1101/2020.01.30.927806v1
The work evaluated single-cell transcriptomes of lung, esophagus, gastric, ileum and colon. The data showed that apart from being highly expressed in organs of the respiratory tract, ACE2 (which acts as receptor for the virus) was also highly expressed in absorptive enterocytes from ileum and colon. These results indicated the digestive system as another potential route for 2019-nCov infection.
Complete genome characterisation of a novel coronavirus associated with severe human respiratory disease in Wuhan, China
https://www.biorxiv.org/content/10.1101/2020.01.24.919183v2
Bronchoalveolar lavage was collected from 7 workers at the Wuhan seafood market. Next generation metagenomic RNA sequencing identified an RNA virus of family Coronaviridae, called at the time WH-Human-1 coronavirus. Phylogenetic analyis showed 89.1% similarity to SARS-like coronaviruses previously sampled from bats in China.
Estimated effectiveness of traveller screening to prevent international spread of 2019 novel coronavirus (2019-nCoV)
https://www.medrxiv.org/content/10.1101/2020.01.28.20019224v2
he study analyzes the impact of travel screening programs on coronavirus spread. They make a model available for interactive use. They estimate that around half of infected travelers will be missed by screening programs, but predict these cases will be those that have not yet developed symptoms and are unaware of exposure.
Potent neutralization of 2019 novel coronavirus by recombinant ACE2-Ig
https://www.biorxiv.org/content/10.1101/2020.02.01.929976v2
The study generated a novel recombinant protein by connecting the extracellular domain of human ACE2 to the Fc region of the human immunoglobulin IgG1. Fusion proteins potently neutralized SARS-CoV and 2019-nCoV in vitro.
Specific ACE2 Expression in Cholangiocytes May Cause Liver Damage After 2019-nCoV Infection
https://www.biorxiv.org/content/10.1101/2020.02.03.931766v1
Describes that a proportion of SARS and 2019-nCoV patients showed signs of liver damage. The study found specific expression of ACE2 in cholangiocytes (epithelial cells of the bile duct), and suggests that the liver damage observed in some infected patients might be due to cholangiocyte dysfunction. The authors suggest addressing potential liver dysfunction in patients during and after hospital care.
Preparedness and vulnerability of African countries against introductions of 2019-nCoV
https://www.medrxiv.org/content/10.1101/2020.02.05.20020792v1
This study evaluated the preparedness and vulnerability of African countries against the risk of importation of 2019-nCoV based on travel volumes from infected provinces in China to African countries. Identified Egypt, Algeria, and South Africa ashaving the highest importation risk. Identified Nigeria, Ethiopia, Sudan, Angola, Tanzania, Ghana, and Kenya as being at moderate risk, but as having high vulnerability. Suggests intensifying surveillance, and prioritizing capacity building.
A database resource for Genome-wide dynamics analysis of Coronaviruses on a historical and global scale
https://www.biorxiv.org/content/10.1101/2020.02.05.920009v1
This work developed a coronavirus database (CoVdb)- an online genomics and proteomics analysis platform. The database annotates the genome of every strain and identifies 780 possible ORFs of all strains available in Genebank. It also provides population genetics analysis, functional analysis and structural analysis on a historical and global scale. Accessed freely at http://covdb.popgenetics.net.
The Novel Coronavirus, 2019-nCoV, is Highly Contagious and More Infectious Than Initially Estimated
https://www.medrxiv.org/content/10.1101/2020.02.07.20021154v1
Initially, the basic reproductive number (R0) was estimated to be 2.2 to 2.7. This study integrates new estimates and high-resolution real-time human travel and infection data with mathematical models, and re-estimates the R0 value as being between 4.7 and 6.6.
Characteristics of lymphocyte subsets and cytokines in peripheral blood of 123 hospitalized patients with 2019 novel coronavirus pneumonia (NCP)
https://www.medrxiv.org/content/10.1101/2020.02.10.20021832v1
Time-varying transmission dynamics of Novel Coronavirus Pneumonia in China
https://www.biorxiv.org/content/10.1101/2020.01.25.919787v2
Proposed that novel coronavirus has higher transmissibility than SARS between humans.
Diarrhea may be underestimated: a missing link in 2019 novel coronavirus
https://www.medrxiv.org/content/10.1101/2020.02.03.20020289v2
The authors suggest that ACE2-expressing small intestinal epithelium cells might be vulnerable to 2019-nCoV infection, and that diarrhea may serve as an indicator for infection. They suggest that clinicians should pay more attention to patients with diarrhea during the outbreak of pneumonia.
The Pathogenicity of SARS-CoV-2 in hACE2 Transgenic Mice
https://www.biorxiv.org/content/10.1101/2020.02.07.939389v3
he study used hACE2 transgenic mice to study the pathogenicity of SARS-CoV-2. They define histopathology in the lungs, specific to transgenice mice and not observed in wild type mice. They propose this mouse model may facilitate the development of therapeutics and vaccines against SARS-CoV-2.
A human monoclonal antibody blocking SARS-CoV-2 infection
https://www.biorxiv.org/content/10.1101/2020.03.11.987958v1
Report of a human monoclonal antibody that neutralizes SARS-CoV-2 (and SARS-CoV). This cross-neutralizing antibody targets a communal epitope on these viruses and offers potential for prevention and treatment of COVID-19.
Hydroxychloroquine and Azithromycin as a treatment of COVID-19: preliminary results of an open-label non-randomized clinical trial
https://www.medrxiv.org/content/10.1101/2020.03.16.20037135v1
This preprint was the first to describe the use of Hydroxychloroquine and Azithromycin to treat COVID-19. It appeared in the journal International Journal of Antimicrobial Agents a day after it was submitted. 42 COVID-19 positive patients were enrolled in this study, 16 of which recieved normal care (control) and 26 receiving the Hydroxychloroquine therapy. Out of these 26, 20 completed the study with 6 of these patients also recieving Azithromycin (antibiotic). At day 6 of treatment, 100% of patients recieving the combination therapy were COVID-19 negative with approximately 50% of the Hydroxychloroquine-only group being COVID-19 negative. In contrast, most of the control were COVID-19 positive. Importantly, this was not a randomised clinical trial and there were numerous issues with the study and the subsequent “peer review” prior to publication. These are outlined fully by Dr Elizabeth Bik (https://scienceintegritydigest.com/2020/03/24/thoughts-on-the-gautret-et-al-paper-about-hydroxychloroquine-and-azithromycin-treatment-of-covid-19-infections/).
Reinfection could not occur in SARS-CoV-2 infected rhesus macaques
https://www.biorxiv.org/content/10.1101/2020.03.13.990226v1
Rhesus macaques previously infected with SARS-CoV-2 could not be reinfected with virus within a period of 28 days after symptoms were alleviated. Conclusions highly exploratory and based on preliminary data gathered from 4 rhesus macaques.
Temporal dynamics in viral shedding and transmissibility of COVID-19
https://www.medrxiv.org/content/10.1101/2020.03.15.20036707v2
Models suggest that COVID-19 Infectiousness peaks at or before symptom onset, and 44% of transmissions could happen before symptom onset.
SARS-CoV-2 specific antibody responses in COVID-19 patients
https://www.medrxiv.org/content/10.1101/2020.03.18.20038059v1
Confirming S1 as specific antigen for SARS-CoV-2 testing, relative to S2 antigen.
Analysis of codon usage and evolutionary rates of the 2019-nCoV genes
https://www.biorxiv.org/content/10.1101/2020.03.25.006569v1
Main results suggest that the higher evolutionary rate observed for genes encoding nucleocapsid, viral replicase and spike proteins, could represent a major barrier in the development of antiviral therapeutics 2019-nCoV.
A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing
Categories: epidemiology , evolutionary biology , pathology , pharmacology and toxicology
Posted on: 27 January 2020 , updated on: 1 April 2020
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