RESUMO
The focused drug repurposing of known approved drugs (such as lopinavir/ritonavir) has been reported failed for curing SARS-CoV-2 infected patients. It is urgent to generate new chemical entities against this virus. As a key enzyme in the life-cycle of coronavirus, the 3C-like main protease (3CLpro or Mpro) is the most attractive for antiviral drug design. Based on a recently solved structure (PDB ID: 6LU7), we developed a novel advanced deep Q-learning network with the fragment-based drug design (ADQN-FBDD) for generating potential lead compounds targeting SARS-CoV-2 3CLpro. We obtained a series of derivatives from those lead compounds by our structure-based optimization policy (SBOP). All the 47 lead compounds directly from our AI-model and related derivatives based on SBOP are accessible in our molecular library at https://github.com/tbwxmu/2019-nCov. These compounds can be used as potential candidates for researchers in their development of drugs against SARS-CoV-2.
RESUMO
ObjectiveTo describe the epidemiological and clinical characteristics of the Coronavirus Disease 2019 (COVID-19) hospitalized patients and to offer suggestions to the urgent needs of COVID-19 prevention, diagnosis and treatment. MethodsWe included 102 confirmed COVID-19 cases hospitalized in Xiangyang No.1 peoples hospital, Hubei, China until Feb 9th, 2020. Demographic data, laboratory findings and chest computed tomographic (CT) images were obtained and analyzed. FindingsAll cases were confirmed by real-time RT-PCR, including 52 males and 50 females with a mean age of 50.38 years (SD 16.86). Incubation time ranged from one to twenty days with a mean period of 8.09 days (SD 4.99). Fever (86[84.3%] of 102 patients), cough (58[57%]), fatigue (28[27%]), shortness of breath (24[23%]), diarrhea (15[15%]), expectoration (13[12%]), inappetence (11[10%]) were common clinical manifestations. We observed a decreased blood leukocyte count and lymphopenia in 21 (20.6%) and 56 (54.9%) patients, respectively. There were 66 (68%) of 97 patients with elevated C-reactive protein levels and 49 (57.6%) of 85 with increased erythrocytes sedimentation rate. Higher levels of procalcitonin and ferritin were observed in 19 (25.3%) of 75 and 12 (92.3%) of 13 patients, respectively. Eight patients were admitted to intensive care unit (ICU), six developed respiratory failure, three had multiple organ failure and three died. The cumulative positivity rate over three rounds of real-time RT-PCR was 96%. One-hundred patients were found with typical radiological abnormalities in two rounds of chest CT scans, indicating a 98% consistency with real-time RT-PCR results. InterpretationMost COVID-19 patients in Xiangyang were secondary cases without sex difference, and the rate of severe case and death was low. Middle-to-old-age individuals were more susceptible to the virus infection and the subsequent development of severe/fatal consequences. The average incubation period was longer among our patients. We recommend prolonging the quarantine period to three weeks. Three times real-time RT-PCR plus two times CT scans is a practical clinical diagnosis strategy at present and should be used to increase the accuracy of diagnosis, thereby controlling the source of infection more effectively.
