In vitro and in vivo evaluation of the main protease inhibitor FB2001 against SARS-CoV-2.

FB2001 is a drug candidate that targets the main protease of SARS-CoV-2 via covalently binding to cysteine 145. In this study, we evaluated the inhibitory activities of FB2001 against several SARS-CoV-2 variants in vitro and in vivo (in mice), and we also evaluated the histopathological analysis and immunostaining of FB2001 on lung and brain which have been rarely reported. The results showed that FB2001 exhibited potent antiviral efficacy against several current SARS-CoV-2 variants in Vero E6 cells, namely, B.1.1.7 (Alpha): EC50 = 0.39 ± 0.01 µM, EC90 = 0.75 ± 0.01 µM; B.1.351 (Beta): EC50 = 0.28 ± 0.11 µM, EC90 = 0.57 ± 0.21 µM; B.1.617.2 (Delta): EC50 = 0.27 ± 0.05 µM, EC90 = 0.81 ± 0.20 µM; B.1.1.529 (Omicron): EC50 = 0.26 ± 0.06 µM and EC50 = 0.042 ± 0.007 µM (in the presence of a P-glycoprotein inhibitor). FB2001 remained potent against SARS-CoV-2 replication in the presence of high concentrations of human serum, which indicating that human serum had no significant effect on the in vitro inhibitory activity. Additionally, this inhibitor exhibited an additive effect against SARS-CoV-2 when combined with Remdesivir. Furthermore, FB2001 significantly reduced the SARS-CoV-2 copy numbers and titers in the lungs and brains in vivo, and alleviated the pathological symptoms. In addition, FB2001 could alleviated local bleeding, erythrocyte overflow, edema, and inflammatory cell infiltration in brain tissue, and inhibitors reducing viral titers and improving inflammation in the brain have been rarely reported. A physiologically based pharmacokinetic model was established and verified to predict the FB2001 concentration in human lungs. When FB2001 was administered at 200 mg twice a day for 5 days, the observed Ctrough ss in plasma and predicted Ctrough ss of lung total concentration were 0.163 and 2.5 µg/mL, which were approximately 9 and 132-fold higher than the EC50 of 0.019 µg/mL (0.042 µM) against Omicron variant. Taken together, our study suggests that FB2001 is a promising therapeutic agent in COVID-19 treatment and can be combined with remdesivir to achieve improved clinical outcomes. Owing to its good safety and tolerability in healthy human (NCT05197179 and NCT04766931), FB2001 has been approved for Phase II/III clinical trial (NCT05445934).

Phylodynamics reveals the role of human travel and contact tracing in controlling the first wave of COVID-19 in four island nations.

New Zealand, Australia, Iceland, and Taiwan all saw success in controlling their first waves of Coronavirus Disease 2019 (COVID-19). As islands, they make excellent case studies for exploring the effects of international travel and human movement on the spread of COVID-19. We employed a range of robust phylodynamic methods and genome subsampling strategies to infer the epidemiological history of Severe acute respiratory syndrome coronavirus 2 in these four countries. We compared these results to transmission clusters identified by the New Zealand Ministry of Health by contact tracing strategies. We estimated the effective reproduction number of COVID-19 as 1-1.4 during early stages of the pandemic and show that it declined below 1 as human movement was restricted. We also showed that this disease was introduced many times into each country and that introductions slowed down markedly following the reduction of international travel in mid-March 2020. Finally, we confirmed that New Zealand transmission clusters identified via standard health surveillance strategies largely agree with those defined by genomic data. We have demonstrated how the use of genomic data and computational biology methods can assist health officials in characterising the epidemiology of viral epidemics and for contact tracing.

Challenges and countermeasures of thoracic surgery in the epidemic of novel coronavirus pneumonia / 中国胸心血管外科临床杂志

@#Since December 2019, a novel coronavirus (2019-nCoV, SARS-CoV-2) pneumonia (COVID-19) outbreak has occurred in Wuhan, Hubei Province, and the epidemic situation has continued to spread. Such cases have also been found in other parts of the country. The spread of the novel coronavirus pneumonia epidemic has brought great challenges to the clinical practice of thoracic surgery. Outpatient clinics need to strengthen the differential diagnosis of ground glass opacity and pulmonary plaque shadows. During the epidemic, surgical indications are strictly controlled, and selective surgery is postponed. Patients planning to undergo a limited period of surgery should be quarantined for 2 weeks and have a nucleic acid test when necessary before surgery. For patients who are planning to undergo emergency surgery, nucleic acid testing should be carried out before surgery, and three-level protection should be performed during surgery. Patients who are planning to undergo emergency surgery in the epidemic area should be confirmed with or without novel coronavirus pneumonia before operation, and perform nucleic acid test if necessary. Surgical disinfection and isolation measures should be strictly carried out. Among postoperative patients, cases with new coronavirus infection were actively investigated. For the rescue of patients with novel coronavirus infection, attention needs to be paid to prevention and treatment and related complications, including mechanical ventilation-related pneumothorax or mediastinal emphysema, and injury after tracheal intubation.

Dynamic evaluation of lung involvement during coronavirus disease-2019 (COVID-19) with quantitative lung CT.

PURPOSE: To identify and quantify lung changes associated with coronavirus disease-2019 (COVID-19) with quantitative lung CT during the disease. METHODS: This retrospective study reviewed COVID-19 patients who underwent multiple chest CT scans during their disease course. Quantitative lung CT was used to determine the nature and volume of lung involvement. A semi-quantitative scoring system was also used to evaluate lung lesions. RESULTS: This study included eighteen cases (4 cases in mild type, 10 cases in moderate type, 4 cases in severe type, and without critical type cases) with confirmed COVID-19. Patients had a mean hospitalized period of 24.1 ± 7.1 days (range: 14-38 days) and underwent an average CT scans of 3.9 ± 1.6 (range: 2-8). The total volumes of lung abnormalities reached a peak of 8.8 ± 4.1 days (range: 2-14 days). The ground-glass opacity (GGO) volume percentage was higher than the consolidative opacity (CO) volume percentage on the first CT examination (Z = 2.229, P = 0.026), and there was no significant difference between the GGO volume percentage and that of CO at the peak stage (Z = - 0.628, P = 0.53). The volume percentage of lung involvement identified by AI demonstrated a strong correlation with the total CT scores at each stage (r = 0.873, P = 0.0001). CONCLUSIONS: Quantitative lung CT can automatically identify the nature of lung involvement and quantify the dynamic changes of lung lesions on CT during COVID-19. For patients who recovered from COVID-19, GGO was the predominant imaging feature on the initial CT scan, while GGO and CO were the main appearances at peak stage.