Potential inhibitors for blocking the interaction of the coronavirus SARS-CoV-2 spike protein and its host cell receptor ACE2.

BACKGROUND: The outbreak of SARS-CoV-2 continues to pose a serious threat to human health and social. The ongoing pandemic of COVID-19 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made a serious threat to public health and economic stability worldwide. Given the urgency of the situation, researchers are attempting to repurpose existing drugs for treating COVID-19. METHODS: We first established an anti-coronavirus drug screening platform based on the Homogeneous Time Resolved Fluorescence (HTRF) technology and the interaction between the coronavirus spike protein and its host receptor ACE2. Two compound libraries of 2,864 molecules were screened with this platform. Selected candidate compounds were validated by SARS-CoV-2_S pseudotyped lentivirus and ACE2-overexpressing cell system. Molecular docking was used to analyze the interaction between S protein and compounds. RESULTS: We identified three potential anti-coronavirus compounds: tannic acid (TA), TS-1276 (anthraquinone), and TS-984 (9-Methoxycanthin-6-one). Our in vitro validation experiments indicated that TS-984 strongly inhibits the interaction of the coronavirus S protein and the human cell ACE2 receptor. Additionally, tannic acid showed moderate inhibitory effect on the interaction of S protein and ACE2. CONCLUSION: This platform is a rapid, sensitive, specific, and high throughput system, and available for screening large compound libraries. TS-984 is a potent blocker of the interaction between the S-protein and ACE2, which might have the potential to be developed into an effective anti-coronavirus drug.

A retrospective analysis from a single center for 60 COVID-19 patients with asymptomatic, mild to moderate, and severe conditions in Wuxi, China.

ABSTRACT: The aim of this study was to retrospectively analyze the clinical data of COVID-19 patients with different severity during February 2020 in Wuxi, China.The present retrospective study included a total of 60 cases who were diagnosed as COVID-19 patients and hospitalized in the Wuxi Fifth People's Hospital during February 2020 to March 2020. Among all patients 14 cases were asymptomatic, 25 cases were with mild stage, 13 cases were with moderate stage, and 8 cases were with severe stage. Basic clinical data as well as clinical characteristics, including temperature, respiratory rate, heart rate, blood gas analysis data, whole blood test data, and the prognosis condition, were collected and analyzed. Statistical analysis was conducted in different severity stage patients.Among the patients, the median temperature gradually increased from the asymptomatic to the severe patients and the median age increased from the mild to the severe patients with statistical difference. The hospitalization duration was the highest in severe patients. Higher heart rate, as well as lower oxygen partial pressure and oxygenation index were observed in severe patients than the other groups. Besides, higher CRP and globulin levels after admission were found in severe patients, and were gradually increased from the asymptomatic patients to the severe patients. On the contrary, the lymphocyte ratio and count was significant lower in severe patients. We also observed higher D-Dimer levels in the severe patients and the difference was statistical. Among all patients, 2 cases (3.33%) died and other patients were all cured after treatment.Statistical difference was mainly found mainly in age, hospitalization duration, temperature, CRP levels, O2 partial pressure and oxygenation index, globulin, lymphocyte ratio, and D-Dimer in patients with different severity. The higher CRP levels, lower O2 partial pressure and oxygenation index, higher globulin, lower lymphocyte ratio, and higher D-Dimer might be associated with the patients' severity.

Quantitative assessment of COVID-19 pneumonia in neonates using lung ultrasound score.

BACKGROUND: Lung ultrasound (LUS) and lung ultrasound score (LUSS) have been successfully used to diagnose neonatal pneumonia, assess the lesion distribution, and quantify the aeration loss. The present study design determines the diagnostic value of LUSS in the semi-quantitative assessment of pneumonia in coronavirus disease 2019 (COVID-19) neonates. METHODS: Eleven COVID-19 neonates born to mothers with COVID-19 infection and 11 age- and gender-matched controls were retrospectively studied. LUSS was acquired by assessing the lesions and aeration loss in 12 lung regions per subject. RESULTS: Most of the COVID-19 newborns presented with mild and atypical symptoms, mainly involving respiratory and digestive systems. In the COVID-19 group, a total of 132 regions of the lung were examined, 83 regions (62.8%) of which were detected abnormalities by LUS. Compared with controls, COVID-19 neonates showed sparse or confluent B-lines (83 regions), disappearing A-lines (83 regions), abnormal pleural lines (29 regions), and subpleural consolidations (2 regions). The LUSS was significantly higher in the COVID-19 group. In total, 49 regions (37%) were normal, 73 regions (55%) scored 1, and 10 regions (8%) scored 2 by LUSS. All the lesions were bilateral, with multiple regions involved. The majority of the lesions were located in the bilateral inferior and posterior regions. LUS detected abnormalities in three COVID-19 neonates with normal radiological performance. The intra-observer and inter-observer reproducibility of LUSS was excellent. CONCLUSIONS: LUS is a noninvasive, convenient, and sensitive method to assess neonatal COVID-19 pneumonia, and can be used as an alternative to the use of diagnostic radiography. LUSS provides valuable semi-quantitative information on the lesion distribution and severity.

Use of a Remote Oncology Pharmacy Service Platform for Patients With Cancer During the COVID-19 Pandemic: Implementation and User Acceptance Evaluation.

BACKGROUND: The COVID-19 outbreak has increased challenges associated with health management, especially cancer management. In an effort to provide continuous pharmaceutical care to cancer patients, Sun Yat-sen University Cancer Center (SYSUCC) implemented a remote pharmacy service platform based on its already existing web-based hospital app known as Cloud SYSUCC. OBJECTIVE: The aim of this study was to investigate the characteristics, acceptance, and initial impact of the Cloud SYSUCC app during a COVID-19 outbreak in a tertiary cancer hospital in China. METHODS: The total number of online prescriptions and detailed information on the service were obtained during the first 6 months after the remote service platform was successfully set up. The patients' gender, age, residence, primary diagnosis, drug classification, weekly number of prescriptions, and prescribed drugs were analyzed. In addition, a follow-up telephonic survey was conducted to evaluate patients' satisfaction in using the remote prescription service. RESULTS: A total of 1718 prescriptions, including 2022 drugs for 1212 patients, were delivered to 24 provinces and municipalities directly under the Central Government of China between February 12, 2020, and August 11, 2020. The majority of patients were female (841/1212, 69.39%), and 90.18% (1093/1212) of them were aged 31-70 years old. The top 3 primary diagnoses for which remote medical prescriptions were made included breast cancer (599/1212, 49.42%), liver cancer (249/1212, 20.54%), and thyroid cancer (125/1212, 10.31%). Of the 1718 prescriptions delivered, 1435 (83.5%) were sent to Guangdong Province and 283 (16.5%) were sent to other provinces in China. Of the 2022 drugs delivered, 1012 (50.05%) were hormonal drugs. The general trend in the use of the remote prescription service declined since the 10th week. A follow-up telephonic survey found that 88% (88/100) of the patients were very satisfied, and 12% (12/100) of the patients were somewhat satisfied with the remote pharmacy service platform. CONCLUSIONS: The remote pharmacy platform Cloud SYSUCC is efficient and convenient for providing continuous pharmaceutical care to patients with cancer during the COVID-19 crisis. The widespread use of this platform can help to reduce person-to-person transmission as well as infection risk for these patients. Further efforts are needed to improve the quality and acceptance of the Cloud SYSUCC platform, as well as to regulate and standardize the management of this novel service.