A growing team of groundbreaking scientists around the world are now sharing their lab notebooks online
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 …
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 …
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 …
Introduction A current focus in the field of antiviral drug discovery are helicases, which are motor enzymes responsible for ATP-dependent nucleic acid duplex unwinding. Helicases of all superfamilies (SF) have stretches of amino acids called motifs, that are conserved within an SF and similar across SFs. For this reason, established helicase inhibitors interacting with these Read More …
My goal is to look for strategies and chemical starting points to inhibit viral helicases, with a primary focus on the SARS-CoV-2 helicase NSP13. In a previous post, I showed that a binding pocket in the human helicase SNRNP200 exploited by an allosteric inhibitor (PDB code 5URK) was absent in SARS-CoV-2. Here, I analyze another Read More …
To develop novel inhibitors for viruses with pandemic potential, we have turned our attention towards targeting their helicases due to their high sequence conservation and essential role in viral replication (Newman et al., Nature communications, 2021). SARS-CoV-2 is especially interesting as its helicase, NSP13, was determined to have druggable binding pockets, some of which are Read More …
This is a summary of a detailed analysis that is available here. Helicases are motor proteins that separate double helices through the hydrolysis of ATP analogues (Fairman-Williams et al., Current Opinion in Structural Biology, 2010). They constitute one of the largest enzyme groups, as multiple varieties of helicases are present in all forms of cellular Read More …
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 …
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 …
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 …
