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Sci Rep ; 12(1): 2420, 2022 02 14.
Article in English | MEDLINE | ID: covidwho-1684102


The zinc finger antiviral protein (ZAP) is known to restrict viral replication by binding to the CpG rich regions of viral RNA, and subsequently inducing viral RNA degradation. This enzyme has recently been shown to be capable of restricting SARS-CoV-2. These data have led to the hypothesis that the low abundance of CpG in the SARS-CoV-2 genome is due to an evolutionary pressure exerted by the host ZAP. To investigate this hypothesis, we performed a detailed analysis of many coronavirus sequences and ZAP RNA binding preference data. Our analyses showed neither evidence for an evolutionary pressure acting specifically on CpG dinucleotides, nor a link between the activity of ZAP and the low CpG abundance of the SARS-CoV-2 genome.

COVID-19/genetics , Dinucleoside Phosphates/genetics , Genome, Viral/genetics , RNA-Binding Proteins/genetics , SARS-CoV-2/genetics , Animals , Base Sequence , Binding Sites/genetics , COVID-19/virology , Dinucleoside Phosphates/metabolism , Evolution, Molecular , Host-Pathogen Interactions/genetics , Humans , Nucleotide Motifs/genetics , Protein Binding , RNA, Viral/genetics , RNA, Viral/metabolism , RNA-Binding Proteins/metabolism , SARS-CoV-2/physiology , Virus Replication/genetics
BMJ Open ; 11(1): e044497, 2021 01 06.
Article in English | MEDLINE | ID: covidwho-1013055


INTRODUCTION: Accurate triage is an important first step to effectively manage the clinical treatment of severe cases in a pandemic outbreak. In the current COVID-19 global pandemic, there is a lack of reliable clinical tools to assist clinicians to perform accurate triage. Host response biomarkers have recently shown promise in risk stratification of disease progression; however, the role of these biomarkers in predicting disease progression in patients with COVID-19 is unknown. Here, we present a protocol outlining a prospective validation study to evaluate the biomarkers' performance in predicting clinical outcomes of patients with COVID-19. METHODS AND ANALYSIS: This prospective validation study assesses patients infected with COVID-19, in whom blood samples are prospectively collected. Recruited patients include a range of infection severity from asymptomatic to critically ill patients, recruited from the community, outpatient clinics, emergency departments and hospitals. Study samples consist of peripheral blood samples collected into RNA-preserving (PAXgene/Tempus) tubes on patient presentation or immediately on study enrolment. Real-time PCR (RT-PCR) will be performed on total RNA extracted from collected blood samples using primers specific to host response gene expression biomarkers that have been previously identified in studies of respiratory viral infections. The RT-PCR data will be analysed to assess the diagnostic performance of individual biomarkers in predicting COVID-19-related outcomes, such as viral pneumonia, acute respiratory distress syndrome or bacterial pneumonia. Biomarker performance will be evaluated using sensitivity, specificity, positive and negative predictive values, likelihood ratios and area under the receiver operating characteristic curve. ETHICS AND DISSEMINATION: This research protocol aims to study the host response gene expression biomarkers in severe respiratory viral infections with a pandemic potential (COVID-19). It has been approved by the local ethics committee with approval number 2020/ETH00886. The results of this project will be disseminated in international peer-reviewed scientific journals.

Biomarkers/metabolism , COVID-19/metabolism , Critical Illness/epidemiology , Emergency Service, Hospital/statistics & numerical data , Pandemics , SARS-CoV-2 , Triage/methods , Adult , COVID-19/epidemiology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prognosis , Prospective Studies , Time Factors