Background: In the fight against COVID 19, the government of India announced a 3 weeks lockdown of the entire country of 1.3 billion people on 24 th March 2020. Methods: One week after the lockdown was announced, we conducted an anonymous online survey of the orthopaedic surgeons in India through social media platforms to assess the impact of the lockdown during COVID 19. The survey had a total of 13 questions with (3e5) options and was designed with an aim to understand the perception and the state of mind of the Orthopaedic surgeons in the lockdown situation. Results: The survey was completed by 611 orthopaedic surgeons from 140 cities in India. There were 22.5% orthopaedic surgeons who said that they were definitely stressed out, and 40.5% who said they were mildly stressed out. As the age decreased, the percentage of orthopaedic surgeons feeling "definitely stressed out" increased. Disruption of life-work balance and uncertainties regarding return to work were other strongly associated factors with the "definitely stressed out" group. Conclusion: The psychological impact of the lockdown during COVID 19 on orthopaedic surgeons may become a potential concern that will require addressal through open discussion. Level of evidence: diagnostic level 4.

DCAF1 is a substrate receptor of two distinct E3 ligases (CRL4 DCAF1 and EDVP), plays a critical physiological role in protein degradation, and is considered a drug target for various cancers. Antagonists of DCAF1 could be used toward the development of therapeutics for cancers and viral treatments. We used the WDR domain of DCAF1 to screen a 114-billioncompound DNA encoded library (DEL) and identified candidate compounds using similarity search and machine learning. This led to the discovery of a compound (Z1391232269) with an SPR K D of 11 μM. Structure-guided hit optimization led to the discovery of OICR-8268 (26e) with an SPR K D of 38 nM and cellular target engagement with EC 50 of 10 μM as measured by cellular thermal shift assay (CETSA). OICR-8268 is an excellent tool compound to enable the development of next-generation DCAF1 ligands toward cancer therapeutics, further investigation of DCAF1 functions in cells, and the development of DCAF1-based PROTACs.

No abstract

No abstract

No abstract