The Story So Far - StructuralGenomicsConsortium/CNP23-SARS-CoV2-RdRp GitHub Wiki

Broad-spectrum antiviral drugs acting on RdRp may block viral replication of different RNA viruses. In this project we design and synthesize potent RdRp-targeting compounds and drug candidates against SARS-CoV-2.

For the RA-0002308-01 original hit: We have ordered the 12 commercially available analogues and designed the plan to re-synthesize the original hit RA-0002308-01 and we're still waiting for the chemicals to start the chemistry as following:

For the original hit RA-0002341-01: 10 analogues have been purchased by the UNC (University of North Carolina) as the 1st step to explore the possible SAR of the original hit, the structure of these analogues is as following:

From the last group of analogues, RA-0002864-01 was the most active analogue.

We were looking further to explore more potent analogues of the original hit RA-0002341-01, however there is a limited number of analogues share the same scaffold that's why only one analogue was purchased as most of other analogues (6 analogues) were not commercially available, the synthetic scheme has been designed and we will start the chemistry in 2024.

See here

Reproducible IC50 Data showed that the analogue RA-0002864-01 of the original hit RA-0002341-01 showed inactive :

received 13122023-UNC_Brown_p7_IC50_231212_v1.pptx

Regarding the original hit: RA-0010958 which showed reactive, the gel-based data showed no inhibition activity for this compound as well as instability has been noticed for this compound when it was left at room temperature (was fuming at RT) and other data received on 29th May 2024 did not show any improved potency or solubility for the selected analogues above that's why we decided to to keep this aside Here is the closed issue which explain the work that have been done for this hit and work on the other series RA-0002308-01 and RA_002341-01.