ABSTRACT
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative agent of Coronavirus Disease 2019 (COVID-19) pandemic. Despite intensive and global efforts to discover and develop novel antiviral therapies, only Remdesivir has been approved as a treatment for COVID-19. Therefore, effective antiviral therapeutics are still urgently needed to combat and halt the pandemic. Viral RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 demonstrates high potential as a reliable target for the development of antivirals. We previously developed a cell-based assay to assess the efficiency of compounds that target SARS-CoV-2 RdRp, as well as their tolerance to viral exoribonuclease-mediated proof-reading. In our previous study, we discovered that 2-((1H-indol-3-yl)thio)-N-phenyl-acetamides specifically targets the RdRp of both respiratory syncytial virus (RSV) and influenza A virus. Thus, we hypothesize that 2-((1H-indol-3-yl)thio)-N-phenyl-acetamides may also have the ability to inhibit SARS-CoV-2 replication by targeting its RdRp activity. In this research, we test a compound library containing 103 of 2-((1H-indol-3-yl)thio)-N-phenyl-acetamides against SARS-CoV-2 RdRp, using our cell-based assay. Among these compounds, the top five candidates strongly inhibit SARS-CoV-2 RdRp activity while exhibiting low cytotoxicity and resistance to viral exoribonuclease. Compound 6-72-2a is the most promising candidate with the lowest EC50 value of 1.41 mu M and highest selectivity index (CC50/EC50) (above 70.92). Furthermore, our data suggests that 4-46b and 6-72-2a also inhibit the replication of HCoV-OC43 and HCoV-NL63 virus in a dose-dependent manner. Compounds 4-46b and 6-72-2a exhibit EC50 values of 1.13 mu M and 0.94 mu M, respectively, on HCoV-OC43 viral replication. However, higher concentrations of these compounds are needed to effectively block HCoV-NL63 replication. Together, our findings successfully identified 4-46b and 6-72-2a as promising inhibitors against SARS-CoV-2 RdRp.
ABSTRACT
Objective: To explore the management strategies for patients with gynecological malignant tumors during the outbreak and transmission of COVID-19. Methods: We retrospectively analyzed the clinical characteristics, treatment, and disease outcomes of three patients with gynecological malignancies associated with COVID-19 in Renmin Hospital of Wuhan University, and proposed management strategies for patients with gynecological tumors underriskof COVID-19. Results: Based on the national diagnosis and treatment protocol as well as research progress for COVID-19, three patients with COVID-19 were treated. Meanwhile, they were also appropriately adjusted the treatment plan in accordance with the clinical guidelines for gynecological tumors. Pneumonia was cured in 2 patients, and one patient died of COVID-19. Conclusions: Patients with gynecological malignant tumors are high-risk groups prone to COVID-19, and gynecological oncologists need to carry out education, prevention, control and treatment according to specific conditions. While, actively preventing and controlling COVID-19, the diagnosis and treatment of gynecological malignant tumors should be carried out in an orderly and safe manner.