Mapping the genetic variations of Alpha- and Betacoronavirus UniProt entries onto SARS-CoV-2 NSP16 crystal structure – Post 6

In my last post, I showed how we found the residues lining the catalytic site of SARS-CoV-2 SAM-dependent m7GpppA-specific 2’-O-methyltransferase (2’-O-MTase), which I refer to as NSP16. In this post, I will share with the diversity dendrograms corresponding to the reviewed entries of the Alpha- and Betacoronavirus genera from the UniProt database. I use a Read More …

The Druggability of SARS-CoV-2 NSP16, the SAM-dependent m7GpppA-specific 2’-O-methyltransferase – Post 5

Following the work on the SARS-CoV-2 main protease, we selected NSP16 as the next target of interest. But what is NSP16? The coronavirus genome size is large, about 30 kb single-stranded positive RNA. The RNA molecule is 5’-capped and has 3’-poly-A tail. The viral RNA is the molecular template that is translated to make viral Read More …

Calculating the change in Gibbs free energy (ddGbind) of inhibitor binding associated with genetic variations of SARS-CoV-2 Main Protease – Post 4

In my last post, I briefly mentioned our work in collaboration with Nicola de Maio from Nick Goldman’s lab, at EMBL’s European Bioinformatics Institute (EBI). What Nicola is doing is filtering out unreliable sequences of SARS-CoV-2 samples before analyzing them for genetic variability at the drug-binding sites of SARS-CoV-2 proteins that we want to investigate. First, Read More …

Mapping the genetic variations of SARS-CoV-2 onto its proteins’ crystal structures – Post 3

In my previous posts (post 1 and post 2), I explained how we found the neighboring residues of the SARS-CoV-2 main protease (MPro) catalytic site, then created a diversity dendrogram of the residues, and looked at three examples of coronavirus MPro structures (SARS-CoV, SARS-CoV-2, MERS). In this post, I explain how we looked at hundreds Read More …

Mapping the genetic variations of SARS-CoV-2 onto its proteins’ crystal structures – Post 2

In my previous post, I explained how we found the surrounding residues lining the catalytic site of the SARS-CoV-2 main protease (MPro) using the available crystal structure from the protein databank (PDB code: 7bqy). Following that step, we wanted to zoom in on a few MPro’s structures bound to inhibitors. We looked at MERS, SARS-CoV, Read More …

Mapping the genetic variations of SARS-CoV-2 onto its proteins’ crystal structures – Post 1

Many people have spent a few months in quarantine because of the emergence of a novel coronavirus, SARS-CoV-2, the pathogen that causes COVID-19. (1) More people around the globe are fighting this virus as the number of cases increase. As of today, May 19, 2020, the number of confirmed cases globally almost reach five million, Read More …

A Gentle Introduction to The Ligandable Genome Project

Previously in our lab, Jiayan Wang et al. worked on a project related to the druggable genome. In her project, she evaluated the druggability of protein domains found in the human genome using protein structures bound to druglike ligands. The left panel in Figure 1 demonstrates her workflow to define ligand binding pockets. To build Read More …

Why EZHIP may be a drug target?

PFA ependymomas are pediatric brain tumors with very poor prognosis. They represent about 10% of all pediatric tumors of the central nervous system (CNS), and up to 30% of CNS tumors in children under 3. (1) 9.4% of PFA tumors aberrantly express EZHIP (aka CXorf67), a protein that inhibits Polycomb repressive complex 2 (PRC2). PRC2 Read More …