Multiple Sequence Alignment and Phylogenetic Tree of Human and Viral Helicases

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 …

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 …

Introduction to Probe My Pathway (PMP)

Introduction to Probe my pathway (PMP): accessible at apps.thesgc.org/pmp/   Despite the sequence of the whole human genome 20 years ago, our knowledge of the human proteome remains fragmented. While ~65% of the human proteome has been investigated in varying degrees, about 35% of the human proteome remains uncharacterized (the ‘dark proteome’). A key obstacle Read More …

Phospholipase C zeta 1 (PLCζ1): a promising target as a non-hormonal contraceptive

Background The Structural Genomics Consortium (SGC) has been funded by the Bill & Melinda Gates Foundation to research Women’s and Children’s Health, focusing on the advancement of drug discovery in reproductive biology and disease, child development, and childhood diseases. The SGC plans to generate protein reagents and chemical probes for several potential drug targets for Read More …

Characterization and Assessment of KCNU1/SLO3 as a Potential Non-hormonal Contraceptive Target

Characterization and Assessment of KCNU1/SLO3 as a Potential Non-hormonal Contraceptive Target Introduction Project Proposal The Structural Genomics Consortium (SGC) has recently embarked on its first research project in reproductive biology as a part of the SGC’s new open science Women’s and Children’s Health Program (WCHP). This program, which was generously funded by the Bill & Read More …

Assessing Ovastacin and Fetuin B as a Non-Hormonal Contraceptive Targets

Background: Ovastacin is an oocyte-specific protease involved in sperm adhesion and fertilization. Research into the ovastacin’s protease function suggest it acts on the post-fertilization cleavage of ZP2 via cortical granule exocytosis1. Cleaved ZP2 then causes hardening of the zona pellucida and is then unable to support further sperm binding2. Zona pellucida regulation is critical for Read More …

TBXT Ligands for Chordoma: Covalent Inhibitors Targeting CYS122 Part B: Quinazolines

In this blog post, I will discuss the progress made on improving the binding affinity of new covalent quinazolines targeting CYS122, as well as some of the directions we are taking to further improve binding affinity to TBXT and reduce binding affinity towards EGFR. The synthetic work has been primarily driven by Zach and our Read More …

Baculovirus expression of FIGLA to characterize as a Non-Hormonal Contraceptive Target

Background The Bill and Melinda Gates Foundation awarded the Structural Genomics Consortium with the SGC Women’s and Children’s Health Initiative in September 2021.  The initiative targets a group of proteins for effective non-hormonal contraceptive agents.  Each target protein will be purified and characterized to screen for possible chemical probes and drug candidates. SGC-UNC was assigned Read More …