Vaccines and therapeutics are urgently needed for the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we screen human monoclonal antibodies (mAb) targeting the receptor binding domain (RBD) of the viral spike protein via antibody library constructed from peripheral blood mononuclear cells of a convalescent patient. The CT-P59 mAb potently neutralizes SARS-CoV-2 isolates including the D614G variant without antibody-dependent enhancement effect. Complex crystal structure of CT-P59 Fab/RBD shows that CT-P59 blocks interaction regions of RBD for angiotensin converting enzyme 2 (ACE2) receptor with an orientation that is notably different from previously reported RBD-targeting mAbs. Furthermore, therapeutic effects of CT-P59 are evaluated in three animal models (ferret, hamster, and rhesus monkey), demonstrating a substantial reduction in viral titer along with alleviation of clinical symptoms. Therefore, CT-P59 may be a promising therapeutic candidate for COVID-19.

Human telomerase reverse transcriptase (hTERT), the catalytic subunit of telomerase, functions to stabilize telomere length during chromosomal replication. Previous studies have shown that hTERT promoter is highly active in most tumor and immortal cell lines but inactive in normal somatic cell types. The use of wild-type hTERT promoter, however, may be limited by its inability to direct high level and cancer cell-specific expression necessary for effective targeted gene therapy. To improve cancer cell specificity and the strength of the hTERT promoter, a modified hTERT, m-hTERT promoter was generated in which additional copies of c-Myc and Sp1 binding sites were incorporated adjacent to the promoter. As assessed using relative lacZ expression, hTERT and m-hTERT promoter activity was significantly upregulated in cancer cells but not in normal cells, and within these upregulated cancer cells, m-hTERT promoter strength was substantially higher than that of the wild-type hTERT. Next, to restrict viral replication to tumor cells, a conditional replication-competent adenoviruses, Ad-TERT-Delta19 and Ad-mTERT-delta19 were generated in which the E1A gene, which is essential for viral replication, was placed under the control of the hTERT and m-hTERT promoter, respectively. While the wild-type Ad-TERT-delta19 replicated in and induced cytopathic effect in cancer and in some normal cell lines, Ad-mTERT-delta19 enhanced viral replication and cytopathic effect only in cancer cells. Furthermore, the growth of established human cervical carcinoma in nude mice was significantly suppressed by intratumoral injection of Ad-mTERT-delta19. Taken together, present results strongly suggest that the use of the m-hTERT promoter is not only useful in the regulation of therapeutic gene expression but also that replication-competent oncolytic adenovirus under the control of the m-hTERT promoter may be a new promising tool for the treatment of human malignancies.

This study mainly evaluated the effectiveness of ozonation toward the enhancement of the removal efficiencies of antibiotic-resistant bacteria (ARB), pB10 plasmid transfer, and pB10 plasmids under different pH and suspended solids (SS) and humic acid concentrations. First, chlorination was tested as a reference disinfection process. Chlorination at a very high dose concentration of Cl2 (75 mg L(-1)) and a long contact time (10 min) were required to achieve approximately 90% ARB and pB10 plasmid transfer removal efficiencies. However, even these stringent conditions only resulted in a 78.8% reduction of pB10 plasmid concentrations. In case of ozonation, the estimated CT (concentration × contact time) value (at C0 = 7 mg L(-1)) for achieving 4-log pB10 plasmid removal efficiency was 127.15 mg·min L(-1), which was 1.04- and 1.25-fold higher than those required for ARB (122.73 mg·min L(-1)) and a model nonantibiotic resistant bacterial strain, E. coli K-12, (101.4 mg·min L(-1)), respectively. In preventing pB10 plasmid transfer, ozonation achieved better performance under conditions of higher concentrations of humic acid and lower pH. Our study results demonstrated that the applicability of CT concept in practice, conventionally used for disinfection, might not be appropriate for antibiotic resistance control in the wastewater treatment process. Further studies should be conducted in wastewater engineering on how to implement multiple barriers including disinfection to prevent ARB and ARG discharge into the environment.