The global outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) necessitates the rapid development of new therapies against coronavirus disease 2019 (COVID-19) infection. Here, we present the identification of 200 approved drugs, appropriate for repurposing against COVID-19. We constructed a SARS-CoV-2–induced protein network, based on disease signatures defined by COVID-19 multiomics datasets, and cross-examined these pathways against approved drugs. This analysis identified 200 drugs predicted to target SARS-CoV-2–induced pathways, 40 of which are already in COVID-19 clinical trials, testifying to the validity of the approach. Using artificial neural network analysis, we classified these 200 drugs into nine distinct pathways, within two overarching mechanisms of action (MoAs): viral replication (126) and immune response (74). Two drugs (proguanil and sulfasalazine) implicated in viral replication were shown to inhibit replication in cell assays. This unbiased and validated analysis opens new avenues for the rapid repurposing of approved drugs into clinical trials.
SARS-CoV-2, which causes COVID-19, was first identified in humans in late 2019 and is a coronavirus which is zoonotic in origin. As it spread around the world there has been an unprecedented effort in developing effective vaccines. Computational methods can be used to speed up the long and costly process of vaccine development. Antigen selection, epitope prediction, and toxicity and allergenicity prediction are areas in which computational tools have already been applied as part of reverse vaccinology for SARS-CoV-2 vaccine development. However, there is potential for computational methods to assist further. We review approaches which have been used and highlight additional bioinformatic approaches and PK modelling as in silico approaches which may be useful for SARS-CoV-2 vaccine design but remain currently unexplored . As more novel viruses with pandemic potential are expected to arise in future, these techniques are not limited to application to SARS-CoV-2 but also useful to rapidly respond to novel emerging viruses.
The global outbreak of SARS-CoV-2 necessitates the rapid development of new therapies against COVID-19 infection. Here, we present the identification of 200 approved drugs, appropriate for repurposing against COVID-19. We constructed a SARS-CoV-2-induced protein (SIP) network, based on disease signatures defined by COVID-19 multi-omic datasets(Bojkova et al., 2020; Gordon et al., 2020), and cross-examined these pathways against approved drugs. This analysis identified 200 drugs predicted to target SARS-CoV-2-induced pathways, 40 of which are already in COVID-19 clinical trials(Clinicaltrials.gov, 2020) testifying to the validity of the approach. Using artificial neural network analysis we classified these 200 drugs into 9 distinct pathways, within two overarching mechanisms of action (MoAs): viral replication (130) and immune response (70). A subset of drugs implicated in viral replication were tested in cellular assays and two (proguanil and sulfasalazine) were shown to inhibit replication. This unbiased and validated analysis opens new avenues for the rapid repurposing of approved drugs into clinical trials.
Background: During the coronavirus disease 2019 (COVID-19) pandemic, the management of acute appendicitis shifted towards non-operative management in the United Kingdom (UK). The open approach was recommended over the laparoscopic approach due to the risk of aerosol generation and subsequent contamination. The aim of this study was to compare the overall management and surgical outcomes of the patients treated for acute appendicitis before and during the COVID-19 pandemic.Materials and Methods: We performed a retrospective cohort study at a single district general hospital in the UK. We compared the management and outcome of the patients diagnosed with acute appendicitis before the pandemic, from March to August 2019, and during the pandemic, from March to August 2020. We looked at the patient demographics, methods of diagnosis, management, and surgical outcomes for these patients. The primary outcome of the study was the 30-day readmission rate. Secondary outcomes included length of stay and post-operative complications.Results: Over the period of six months, a total of 179 patients were diagnosed with acute appendicitis in 2019 (
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