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HR Business Services Email Human Resources Services: employmentservices@ualberta.ca IC50 measurements have shown that GC373 and GC376 inhibit SARS-COV Mpro and SARS-CoV-2 Mpro in vitro at nanomolare concentrations (Figure 1b, c). For SARS-CoV-2 Mpro, IC50 for GC373 and GC376, 0.40 ± 0.05 m and 0.19 ± 0.04 m. This corresponds to GC376 studies with Mpro of related viruses. For FCoV Mpro, the IC50 for the GC376 was 0.49 ± 0.07 m, while for the GC376, the IC50 was 1.33 ± 0.19 m and 1.44 ± 0.38 m12 for the GC376. In SARS-CoV Mpro, we observed an improvement in IC50, which was largely inhibited by both compounds, with GC373 and GC376 being 0.070 ± 0.02 m and 0.05 ± 0.01 m, respectively. The bisulfite additive GC376 shows slightly higher efficacy for both enzymes than for free adehhyde. Our in vitro ic50 for GC373 and GC376 reflect a close link for VOC-2 Mpro compared to other inhibitors tested in vitro, z.B. ebselen (IC50 0.67 `M)16, tideglusib (IC50 1.55 `M)16, carmofur (IC50 1.82 `M) 16, disulfiram (IC50 9.35 `M)16, shikonin (IC50 15.75 `M) 16, PX-12 (IC50 21.39 `M)16. GC373 and GC376 are also more potent than recently reported ketoamide inhibitors (IC50 of the leaded compound is 0.67 m)15. Recently, a related peptidyl inhibitor was reported with a warhead similar to ours, but with an indole group in the P3 position and an IC50 of 0.05 ± 0.005 m18. However, this link has not proven its effectiveness in animals, as is the case with GC376. Recent analyses of the crystalline structure have reported differences between residues between the Dimer interface of SARS-CoV-2 Mpro versus SARS-CoV Mpro 15.

Previous mutagenesis studies that modified residues at the Dimer interface of SARS-COV Mpro, and in particular a T285A variant improved catalytic activity 3.6 times21. There is a alanine in SARS-CoV-2 T285. and in keeping with this, our analysis shows that the catalytic fluctuation rate for SARS-CoV-2 Mpro (135 ± 6 min-1) is almost five times faster than SARS-CoV Mpro (30 ± 2 min-1) with our Abz-SVTLQSG-TyrNO2R substrate (Table 1). With this FRET substrate, we have higher catalytic efficacy with SARS-CoV-2 Mpro (1.8 ± 0.4 min-1-M-1) compared to SARS-CoV Mpro (0.6 ± 0.2 min 1 M.1). This finding contrasts with recent reports, in which no difference in catalytic efficacy was observed between SARS-COV Mpro and SARS-COV-2 Mpro using another substrate: 3011 ± 294 s-1 M-1 (0.18 ±0.02 min 1 M`1) and 3426 ± 416.9 s`1 M`1 (0.2 ± 0.03 min.1 `M`1`1`15. It remains to be seen whether this affects the virulence of SARS-CoV-2. The Faculty and Human Relations held two briefings on updates to the AASUA 2018-2020 collective agreement. Employees who manage and interpret the agreement may find these slides useful in communicating changes, carrying out their work, and updating internal information and policies.

Let the faculty and staff know if you have any questions or are interested in an upcoming information meeting on fsrel@ualberta.ca. We can also cut the presentation out on certain employee groups. E-mail from the Graduate Students` Association: gsa.vplabour@ualberta.ca We are constantly striving to improve the usefulness of these resources.