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The COVID-19 pandemic continues to pose a substantial threat to human lives and is likely to do so for years to come. Despite the availability of vaccines, searching for efficient small-molecule drugs that are widely available, including in low- and middle-income countries, is an ongoing challenge. In this work, we report the results of a community effort, the “Billion molecules against Covid-19 challenge”, to identify small-molecule inhibitors against SARS-CoV-2 or relevant human receptors. Participating teams used a wide variety of computational methods to screen a minimum of 1 billion virtual molecules against 6 protein targets. Overall, 31 teams participated, and they suggested a total of 639,024 potentially active molecules, which were subsequently ranked to find ‘consensus compounds’. The organizing team coordinated with various contract research organizations (CROs) and collaborating institutions to synthesize and test 878 compounds for activity against proteases (Nsp5, Nsp3, TMPRSS2), nucleocapsid N, RdRP (Nsp12 domain), and (alpha) spike protein S. Overall, 27 potential inhibitors were experimentally confirmed by binding-, cleavage-, and/or viral suppression assays and are presented here. All results are freely available and can be taken further downstream without IP restrictions. Overall, we show the effectiveness of computational techniques, community efforts, and communication across research fields (i.e., protein expression and crystallography, in silico modeling, synthesis and biological assays) to accelerate the early phases of drug discovery.

Due to the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, there is an urgent need for novel therapies and drugs. We conducted a large-scale virtual screening for small molecules that are potential CoV-2 inhibitors. To this end, we utilized "ChemAI", a deep neural network trained on more than 220M data points across 3.6M molecules from three public drug-discovery databases. With ChemAI, we screened and ranked one billion molecules from the ZINC database for favourable effects against CoV-2. We then reduced the result to the 30,000 top-ranked compounds, which are readily accessible and purchasable via the ZINC database. Additionally, we screened the DrugBank using ChemAI to allow for drug repurposing, which would be a fast way towards a therapy. We provide these top-ranked compounds of ZINC and DrugBank as a library for further screening with bioassays at https://github.com/ml-jku/sars-cov-inhibitors-chemai., Additional results added. Various corrections to formulations and typos

Single-shot devices have been developed to simplify pulmonary vein isolation (PVI). Randomized studies of the second-generation cryoballoon (CB 2nd) demonstrated excellent results. There are limited data comparing results of circular pulmonary vein ablation catheter (PVAC) with conventional RF ablation or CB for PVI. Using a sequential registry cohort and a prospective randomized study, we aimed to compare the acute and long-term results of CB 2nd and PVAC Gold. In the registry, consecutive patients with paroxysmal atrial fibrillation (AF) undergoing their first PVI were included. The preferred method used was PVAC Gold in 2014 and CB 2nd in 2015. Subsequently, a randomized study (PVAC vs. CB 2nd) was performed. Ablation success was measured as freedom of AF or atrial tachycardias (AT) off antiarrhythmic drugs. In the registry cohort, PVAC Gold was used in 60 patients and CB 2nd in 56 patients (age 66 ± 11 years, 52% male, LAD 43 ± 6). In the randomized study, 20 patients were treated with PVAC Gold and 22 with CB 2nd (age 67 ± 9; 43% men, LAD 40 ± 7 mm). During a mean follow up of 13.2 ± 3.6 months, success was 54% in PVAC Gold patients and 81% in CB 2nd cases (p = 0.001). In the randomized study 12 months success was 50% versus 86%, p

Abstract—Background: Unconscious patients with severe trauma often require urgent endotracheal intubation. In trauma victims with possible cervical spine injury, any movement of the head and neck should be avoided. Study Objectives: We investigated the effect of GlideScope videolaryngoscopy on cervical spine movement compared with conventional laryngoscopy in anesthetized patients with unsecured cervical spines. Methods: Sixty patients scheduled for elective surgery with general anesthesia and without anticipated airway problemswereenrolledin the studyafter ethics committee approval and written informed consent. Intubation was performed with videolaryngoscopy (GlideScope, Verathon Inc., Bothell, WA) or conventional laryngoscopy (MacIntosh). Using video motion analysis with a lateral view, the maximum extension angle a was measured with reference to anatomical points (baseline and line drawn from processus mastoideus to os frontale [glabella]). Values were analyzed using Mann Whitney U-tests. Results: The deviation of a was a median 11.8 in the videolaryngoscope group and 14.3 in the conventional group (p = 0.045), with a maximum of 19.2 (videolaryngoscopy) vs. 29.3 (conventional). Intubation by physicians with some experience in videolaryngoscopy was associated with a reduced angle deviation (a = 10.3) compared to inexperienced physicians (12.8, p = 0.019). Intubation time was a median 24 s (min/max 12/75 s) in the MacIntosh group and 53 s (min/max 28/210 s) in the GlideScope group. In 3 patients randomized to the conventional group in whom conventional intubation failed, intubation could be successfully performed using videolaryngoscopy. Conclusion: GlideScope videolaryngoscopy reduces movements of the cervical spine in patients with unsecured cervical spines and therefore might reduce the risk of secondary damage during emergency intubation of patients with cervical spine trauma. 2013 Elsevier Inc.