The next target: SARS-CoV-2 RNA-dependent RNA polymerase and Its Druggability – Post 19

Previously we reported our analysis on the structural diversity of binding pockets found on the SARS-CoV-2 main protease, methyltransferase, and papain-like protease, macrodomain. We then shifted our focus on the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp). SARS-CoV-2 is a positive-strand RNA virus, depending on its multi-subunit machinery to replicate its RNA. The catalytic subunit of RdRp Read More …

Calculating the change in Gibbs free energy (ddGbind) of an improved alpha-ketoamide inhibitor binding associated with genetic variations of SARS-CoV-2 main protease – post18

Since we posted our analysis of genetic variation of SARS-CoV-2 main protease (MPro) with inhibitor N3 (PDB: 7bqy), there have been other inhibitors co-crystallized with the MPro (PDB: 6lze, PDB: 6m0k, and PDB: 6y2f). In my last post, I talked about the two inhibitors, 11a and 11b (PDB: 6lze, PDB: 6m0k) and in today’s post, Read More …

Structure and X-ray Fragment screening of SARS-Cov-2 helicase (Nsp13)

My name is Joseph Newman and I have been working in Lab of Opher Gileadi at SGC Oxford since 2013 mainly on targeting DNA repair factors as synthetic lethal targets for early stage development of new cancer therapeutics. Like many scientists my normal laboratory based research activities were disrupted by the lockdown, and when Opher Read More …

Back to SARS-CoV-2 Main Protease: Calculating the change in Gibbs free energy (ddGbind) of two peptidomimetic aldehyde Inhibitors binding associated with genetic variations of SARS-CoV-2 main protease – post17

Since we posted our analysis of genetic variation of SARS-CoV-2 main protease (MPro) with inhibitor N3 (PDB: 7bqy), there have been other inhibitors co-crystallized with the MPro (PDB: 6lze and PDB: 6m0k). MPro acts like a scissor by cutting SARS-CoV-2 polyproteins into functional pieces, making it a critical target for antiviral therapies against SARS-CoV-2. In Read More …

Generation of stable mammalian cell lines for the expression of proteins related to COVID-19 through random integration

Background: Scientists centred around University of Oxford came together in the current COVID-19 pandemic to contribute to relevant studies collaboratively. Researchers with no prior experience in virology studies, myself included, had volunteered our time to contribute whichever way we can based on our field of expertise. The Biotech team of SGC Oxford, headed by Nicola Read More …

Predicting the effect of all possible mutations at nsp3-Mac1 ADPr-binding site on ADPr binding – Post 16

In my last post, I showed you the genetic variants at the ADP-ribose (ADPr) binding site of SARS-CoV-2 nsp3-Mac1 and the predicted effects of those mutations on ADPr binding with Mac1. Next, we wanted to assess the effect of all possible mutations at the sidechains lining the ADPr binding site of nsp3-Mac1 and how that Read More …

Genetic variability at the ADP-ribose Binding Site of the SARS-CoV-2 nsp3-Mac1 and predicted effects of mutations on ADP-ribose binding – Post 15

In two of my previous posts 13 and 14, I showed how we found the residues lining the ADP ribose (ADPr) binding site of SARS-CoV-2 nsp3-Mac1 and we looked at the variability of this site across Alpha- and Betacoronavirus entries from UniProt. In addition to the UniPro sequences, we were interested in looking at variants Read More …

Mapping the genetic variations of Alpha- and Betacoronavirus UniProt entries onto SARS-CoV-2 nsp3-Mac1 crystal structure – Post 14

In my last post, I showed how we found the residues lining the ADP-ribose (ADPr) binding site of SARS-CoV-2 nsp3-Mac1 using its crystal structure (PDB: 6w02). In this post, I will show the sequence diversity across UniProt entries from the Alpha- and Betacoronavirus genera and map that to the Mac1’s ADPr binding site using the Read More …

The next target: SARS-CoV-2 Macrodomain and Its Druggability – Post 13

Previously we reported our analysis on the structural diversity of binding pockets found on the SARS-CoV-2 Main protease, methyltransferase, and papain-like protease. We then shifted our focus on the SARS-CoV-2 macrodomain (nsp3-Mac1). There are six macrodomain classes based on structural similarity. Most viral macrodomains fall into the MacroD-like family the same as human homologs MacroD1 Read More …

The next target: SARS-CoV-2 Papain-like Protease’s Catalytic Site and Its Druggability – Post 9

Following our work on SARS-CoV-2 NSP16, we shifted our focus on SARS-CoV-2 Papain-like protease (PLPro) which is a cysteine protease. A protease is an enzyme that breaks down proteins into smaller polypeptides or single amino acids. Similarly, PLPro recognizes specific tetrapeptide motif (LXGG) found in-between the fused viral proteins and cuts them at those particular Read More …