ABSTRACT
The pandemic of coronavirus disease 2019 (COVID-19) has urgently necessitated the development of antiviral agents against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The 3C-like protease (3CLpro) is a promising target for COVID-19 treatment. Here, we report the new class of covalent inhibitors for 3CLpro possessing chlorofluoroacetamide (CFA) as a cysteine reactive warhead. Based on the aza-peptide scaffold, we synthesized the series of CFA derivatives in enantiopure form and evaluated their biochemical efficiencies. The data revealed that 8a (YH-6) with R configuration at the CFA unit strongly blocks the SARS-CoV-2 replication in the infected cells and this potency is comparable to that of nirmatrelvir. The X-ray structural analysis shows that 8a (YH-6) forms a covalent bond with Cys145 at the catalytic center of 3CLpro. The strong antiviral activity and sufficient pharmacokinetics property of 8a (YH-6) suggest its potential as a lead compound for treatment of COVID-19.
ABSTRACT
Introduction: Physical assessment training is included in many 6-year training programs for pharmacists.<br>Method: To clarify the effects of this training for developing the professional abilities of pharmacists and for increasing the students’ motivation for learning, we investigated changes in students’ attitudes before and after physical assessment training by means of a questionnaire, whose free descriptions were evaluated with a text-mining approach.<br>Results: After training, the percentage of students who believed they needed to acquire the knowledge and skills of physical assessment increased significantly. Furthermore, the motivation for learning increased.<br>Discussion: We believe that physical assessment training makes students aware of the importance of the contribution of physical assessment to drug therapy and increases students’ motivation for learning.
