FDA-approved Pralatrexate identified by virtual drug screening inhibits SARS-CoV-2 replication in vitro (preprint)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic poses serious threats to the global public health and leads to an unprecedented worldwide crisis. Unfortunately, no effective drugs or vaccines are available till now. Since the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 is a promising therapeutic target, a deep learning and molecular simulation based hybrid drug screening procedure was proposed and applied to identify potential drug candidates targeting RdRp from 1906 approved drugs. Among the four selected FDA-approved drug candidates, Pralatrexate and Azithromycin were confirmed to effectively inhibit SARS-CoV-2 replication in vitro with EC50 values of 0.008µM and 9.453 µM, respectively. For the first time, our study discovered that Pralatrexate is able to potently inhibit SARS-CoV-2 replication with a stronger inhibitory activity than Remdesivir within the same experimental conditions. The paper demonstrates the feasibility of accurate virtual drug screening for inhibitors of SARS-CoV-2 and provides potential therapeutic agents against COVID-19.

Changes in CT manifestations of patients with mild to moderate coronavirus disease 2019 in a Fangcang Shelter Hospital (preprint)

Objectives: To provide a reference for CT imaging changes for patients discharged from a Fangcang shelter hospital, a large-scale, temporary hospital for the centralized treatment of patients with mild to moderate Coronavirus disease 2019 (COVID-19) to provide essential functions (isolation, triage, basic medical care, frequent monitoring and rapid referral, essential living and social engagement) to them..Methods: Patients with mild to moderate COVID-19 admitted to the Wuchang Fangcang Shelter Hospital who had undergone pre-discharge and previous CT scans were included. Changes in the CT imaging features were defined as progression, no change, improvement or recovery. Basic patient information was obtained, and imaging signs were compared between the two CT scans.Results: A total of 83 patients were included. The median age was 53 years old. The course of disease was 28.3±10.7 days. CT imaging changes indicated progression, no change, improvement, and recovery in 3, 12, 66, and 2 patients, respectively. Between the two CT scans, the imaging signs showed a significant reduction in consolidation, a significant increase in fibrosis, and a reduction or / and thinning of ground-glass opacities. None of the patients showed signs of deterioration on follow-up and thus did not need to return to the hospital for treatment.Conclusion: In the COVID-19 Fangcang shelter hospital, given the shortage of medical staff and lack of medical resources, CT imaging diagnostic methods can be used to accurately discharge patients who had met the discharge criteria for isolation and observation from the Fangcang Shelter Hospital.