A growing team of groundbreaking scientists around the world are now sharing their lab notebooks online
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 …
Today’s post focuses on another protein encoded by many coronaviruses, the non-structural protein 15 (nsp15), an endoribonuclease. Nsp15 is a nidoviral RNA uridylate-specific endoribonuclease (NendoU) with C-terminal catalytic activity. This protein belongs to the EndoU family, and they all carry an RNA endonuclease activity to produce 2’-3’ cyclic phosphodiester and 5’-hydroxyl termini. (Kim et al. Read More …
Today’s post focuses on another protein encoded in open reading frame 1a (ORF1a) of many coronaviruses, the non-structural protein 9 (nsp9). Nsp9 is thought to mediate viral replication. In SARS-CoV-1, nsp9’s role has been highlighted as a single-stranded RNA-binding subunit. (Egloff et al., 2004) The structure of SARS-CoV-2 nsp9 was solved in both apo and Read More …
Hello and happy new year! I am back from my winter break and starting to get back to research. If you have followed my previous posts, you know that I have posted the druggability and genetic variability analysis of several protein targets of SARS-CoV-2. There are a few targets that I will be posting in Read More …
One of the important enzymes in the replication cycle of the SARS-CoV-2 virus is the helicase, which is also known as non-structural protein 13 (nsp13). During the viral life cycle, the holo-RNA-dependent RNA polymerase, also known as nsp12, is thought to coordinate with several additional factors, including the nsp13 helicase (Snijder et al., 2016; Sola Read More …
