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. Email from the Graduate Students` Association: gsa.vplabour@ualberta.ca resources for superiors and managers to help enforce collective agreements and textbooks. Many drugs were originally developed to inhibit SARS-CoV Mpro3, but the 2002 SARS outbreak was controlled by public health measures and these compounds were never allowed. GC376 has been used to successfully treat PPF in cats because its degradation product, GC373, effectively inhibits FCoV Mpro. Analogues of these drugs also inhibited MERS CoV Mpro and blocked viral replication in cells at an EC50 of 0.5 M14. Our studies show that GC376 and GC373 are effective inhibitors of SARS-CoV-2 Mpro. Consistent with previous studies that show that GC373 and GC376 have a broad specificity to coronavirus and calcivirus Mpro (Additional Table 2) 10,13,14,22. It is clear that these drugs need to be advanced quickly in human studies for COVID-19.
SARS-COV-2 is the cause of COVID-19 and is a virus with a significant mutation rate23. In some patients too, the virus persists for more than 2 months with a possibility of re-infection24.