Publication of Clinical Trials on Medicinal Products: A Follow-Up Study

Background: Clinical research should provide reliable evidence to clinicians, health policy makers and researchers, which is only possible once the results are made transparently available. The present research aims to investigate factors influencing publication rates, time and characteristics of clinical trials on medicinal products and to assess the degree of accessibility of trial results on a country level. Methods: Clinical trials authorized in Hungary in the year of 2012 were followed until publication and/or June 2020. Corresponding scientific publications were searched via clinical trial registries, Pubmed (MEDLINE) and Google. Results: Out of 330 clinical trials authorized in 2012, a total of 232 trials were completed for more than 1 year in June 2020. The proportion of industry-initiation was high (97%). Time to publication was 21 (22) months [median (IQR)]. Time to publication was significantly shorter when trials involved both European and non-European countries (p<0.001), and when registered in both EU CTR and clinicaltrials.gov (p<0.001) based on survival analyses. A significant amount (24.1%) of unpublished clinical trial results were accessible in a trial register. A total of 70.93% of available publications were published “open access”. Publications with domestic co-authors contribute to the research output of a country. In our study only 21.5% of the identified publications had a Hungarian author. Conclusions: We encourage academic researchers to plan, register and conduct trials on medicinal products. Registries should be considered as an important source of information of clinical trials results. Measurable domestic scientific impact of trials on medicinal products need further improvement

Semisynthetic teicoplanin derivatives with dual antimicrobial activity against SARS-CoV-2 and multiresistant bacteria

Patients infected with SARS-CoV-2 risk co-infection with Gram-positive bacteria, which severely affects their prognosis. Antimicrobial drugs with dual antiviral and antibacterial activity would be very useful in this setting. Although glycopeptide antibiotics are well-known as strong antibacterial drugs, some of them are also active against RNA viruses like SARS-CoV-2. It has been shown that the antiviral and antibacterial efficacy can be enhanced by synthetic modifications. We here report the synthesis and biological evaluation of seven derivatives of teicoplanin bearing hydrophobic or superbasic side chain. All but one teicoplanin derivatives were effective in inhibiting SARS-CoV-2 replication in VeroE6 cells. One lipophilic and three perfluoroalkyl conjugates showed activity against SARS-CoV-2 in human Calu-3 cells and against HCoV-229E, an endemic human coronavirus, in HEL cells. Pseudovirus entry and enzyme inhibition assays established that the teicoplanin derivatives efficiently prevent the cathepsin-mediated endosomal entry of SARS-CoV-2, with some compounds inhibiting also the TMPRSS2-mediated surface entry route. The teicoplanin derivatives showed good to excellent activity against Gram-positive bacteria resistant to all approved glycopeptide antibiotics, due to their ability to dually bind to the bacterial membrane and cell-wall. To conclude, we identified three perfluoralkyl and one monoguanidine analog of teicoplanin as dual inhibitors of Gram-positive bacteria and SARS-CoV-2