Background on COVID-19 Sample Clauses

Background on COVID-19. ‌ In December 2019, a novel coronavirus (subsequently named SARS-CoV2) was detected in 3 patients with pneumonia connected to the cluster of acute respiratory illness cases from Wuhan, China. By the end of February 2020, multiple countries were experiencing sustained local transmission and is now a world-wide pandemic and global health crisis. The most commonly reported clinical symptom in laboratory-confirmed cases was fever (88%), dry cough (68%), fatigue (38%), sputum production (33%), dyspnea (19%), sore throat (14%), headache (14%) and myalgia or arthralgia (15%). Less common symptoms were diarrhea (4%) and vomiting (5%). About 80% of reported cases in China had mild to moderate disease (including non-pneumonia and pneumonia cases), 13.8% had severe disease (as defined in this protocol) and 6.1% were critical (respiratory failure, septic shock, and/or multiple organ dysfunction/failure). Current estimates suggest a median incubation period from 5 to 6 days for SARS-CoV2, with a range from 1 to up to 14 days. A recent modelling study confirmed that it remains prudent to consider the incubation period of up to 14 days. Xxxxxx estimates for final case fatality risk for COVID-19 are still lacking and biased due to incomplete outcome data and the fact that initial detections were of mostly severe cases in most Confidential Page 25 of 74 ‌‌‌‌‌ Activity of Selinexor and other SINE compounds in models of Inflammation and Viral Infection Selinexor (MW 443.3) and verdinexor (MW 442.3) are closely related molecules that differ by one atom. They have similar chemical, pharmacological and pharmacokinetic properties. Both are potent (Ki < 10 nM) and highly selective inhibitors of XPO1. Both compounds form slowly reversible covalent bonds with cysteine-528 of XPO1 leading to its inactivation, and both are orally bioavailable compounds with no known drug-drug interactions. Preclinically, selinexor has been most intensively studied in cell lines and models of neoplastic diseases, whereas verdinexor has been studied most intensively in viral and autoimmune disorders (Appendix 1). Over 200 XPO1 cargo proteins have been identified including proteins with regulatory roles in inflammatory response and many viral proteins including severe acute respiratory syndrome coronavirus (SARS-CoV2) proteins (Zhou 2020). A variety of viruses produce proteins that require nuclear export to carry out their functions. SARS-CoV2, including nucleoprotein (N), protein 9b, Orf6, and potentia...
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