Efficient Synthesis of Acyclic and Cyclic Pyrazoles for Evaluation as Antiviral nsp2 Protease Inhibitors

Pyrazole (E)-vinyl sulfone 3 was identified as a potential covalent CHIKV nsp2 protease inhibitor from a high throughput screen in the READDI Antiviral Drug Discovery Center at UNC.1 Initial re-synthesis of the hit compound yielded a mixture of acyclic (3) and cyclic sulfones (4) (Scheme 1), which were identified by 1D and 2D NMR, but Read More …

AViDD Filters: Compound Filtering SOP for Hit to Lead

High throughput screening (HTS) is a powerful technique for identifying potential drug candidates from large libraries of compounds. However, many compounds that show activity in HTS are false positives or may not be suitable for further development. Therefore, it is important to apply various filters to eliminate compounds that have undesirable properties, such as poor Read More …

GRC Poster: Identification of SARS-CoV-2 helicase inhibitors by large-scale virtual screening

by Mohammad Anwar Hossain1, Konstantin Popov2, Sumera Perveen3, Kesatebrhan Haile Asressu1, Kenneth Hugh Pearce Jr.2, Cheryl Arrowsmith3, Peter Brown1, Alexander Tropsha4, Tim Willson1 1Structural Genomics Consortium, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 2CICBDD, UNC Eshelman School of Pharmacy; 3The Structural Genomics Consortium, University of Toronto, Canada; 4CBMC, UNC Eshelman Read More …

Release of The Kinase Chemogenomic Set 2.0 (KCGS2.0)

Introduction Situation Kinases are useful for drug discovery – many opportunities! Kinase by kinase probe development is important, but it will take too long to discover a probe for each kinase Disease relevant phenotypic assays need smart compounds sets Numerous high quality kinase inhibitors exist in the literature and in company collections Kinases are “connected” Read More …

Identification of N-oxide containing helicase inhibitors by large-scale virtual screening

SARS-CoV-2 Helicase (NSP13) as a drug target: The pandemic caused by SARS-CoV-2 is not over yet but instead has transformed into a chronic illness. So far, the expedited effort on drug development produced Mpro targeting drugs (Paxlovid) and repurposed RdRp inhibitor Molnupiravir. For effective long-term treatment, we intend to discover complementary antivirals targeting replication machinery Read More …

Helicase inhibitors for SARS-CoV-2 NSP13

In searching for novel drugs that will treat future viral pandemics, the AViDD program has prioritized viral proteases, helicases, and RNA-dependant RNA polymerases (RdRps) as key targets in the fight to control viral replication. At the time of writing, several drugs are either in the clinic or on the market for SARS-CoV-2 proteases and RdRps, Read More …

Thiazole-based helicase inhibitors targeting SARS-CoV-2

Introduction: The outbreak of COVID-19 demonstrated the scarcity of drugs in the development pipeline to decrease the mortality and morbidity caused by the new pathogenic SARS-CoV-2 virus. Despite the improved diagnosis and screening processes, broad directly-acting anticoronavirus drugs were not immediately available to treat viral infections. In response to this health threat, the Rapidly Emerging Read More …