Druggability and Genetic Variability of the Catalytic and Allosteric Sites of SARS-CoV-2 nsp14 Across Coronaviruses and SARS-CoV-2 Samples

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 …

Druggability and Genetic Variability of the ATPase Site and Central Channel of SARS-CoV-2 nsp13 Helicase Across Coronaviruses and SARS-CoV-2 Samples – Post 23

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 …

Druggability and Genetic Variability of the ADP-bound Pocket of SARS-CoV-2 RNA-dependent RNA polymerase NiRAN domain Across Coronaviruses and SARS-CoV-2 Samples – Post 22

The RNA-dependent RNA-polymerase (RdRp) also known as non-structural protein 12 (nsp12) is the target of antiviral agent remdesivir. Nsp12 has an important role in viral genome replication and transcription. (Chen et al., 2020)  Chen et al. identified a new pocket on the N-terminal extension of nsp12 occupied by ADP-Mg2+ after solving the structure of the helicase-polymerase complex. This ADP-bound pocket is on the N-terminal nidovirus RdRp-associated nucleotidyltransferase (NiRAN) domain which Read More …

Genetic Variability at An Allosteric site of SARS-CoV-2 RNA-dependent RNA polymerase Across Coronaviruses and SARS-CoV-2 Samples – Post 21

SARS-CoV-2 is a positive-strand RNA virus, depending on its multi-subunit machinery to replicate its RNA. This machinery is known as RNA-dependent RNA polymerase (RdRp). The catalytic subunit of RdRp, which is the core component of this machinery, is called nsp12. Nsp12 has little catalytic activity on its own and relies on accessory subunits to have Read More …

Genetic Variability at the Remdesivir-binding Pocket of SARS-CoV-2 RNA-dependent RNA polymerase Across Coronaviruses and SARS-CoV-2 Samples – Post 20

In my previous post 19, I showed how we assessed the druggability of the remdesivir-binding site of SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) and determined the residues lining that site. In this post, we analyze the genetic diversity of RdRp catalytic site across Alpha- and Betacoronavirus entries from UniProt and among SARS-CoV-2 samples. In the context Read More …

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 …

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 …

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 …