tetano
Editor, Senior Moderator
J Struct Biol
. 2020 Jul 9;107575.
doi: 10.1016/j.jsb.2020.107575. Online ahead of print.
SARS-CoV and SARS-CoV-2 Main Protease Residue Interaction Networks Change When Bound to Inhibitor N3
Jeddidiah W D Griffin[SUP] 1 [/SUP]
Affiliations
Abstract
COVID-19 is a respiratory disease caused by the coronavirus SARS-CoV-2. SARS-CoV-2 has many similarities with SARS-CoV. Both viruses rely on a protease called the main protease, or M[SUP]pro[/SUP], for replication. Therefore, inhibiting M[SUP]pro[/SUP] may be a successful strategy for treating COVID-19. Structures are available in the Protein Data Bank of the main proteases of SARS-CoV and SARS-CoV-2 with and without inhibitor N3. Comparing these structures revealed residue interaction network changes associated with N3 inhibition. Comparing network clustering with and without inhibitor N3 identified the formation of a cluster of residues 17, 18, 30-33, 70, 95, 98, 103, 117, 122, and 177 as a network change in both viral proteases when bound to inhibitor N3. Betweenness and stress centrality differences as well as differences in bond energies and relative B-factors when comparing free M[SUP]pro[/SUP] to inhibitor-bound M[SUP]pro[/SUP] identified residues 131, 175, 182, and 185 as possibly conformationally relevant when bound to the inhibitor N3. Taken together, these results provide insight into conformational changes of betacoronavirus M[SUP]pro[/SUP]s when bound to an inhibitor.
Keywords: 2019-CoV; 3CLpro; COVID-19; M(pro); betweenness.
. 2020 Jul 9;107575.
doi: 10.1016/j.jsb.2020.107575. Online ahead of print.
SARS-CoV and SARS-CoV-2 Main Protease Residue Interaction Networks Change When Bound to Inhibitor N3
Jeddidiah W D Griffin[SUP] 1 [/SUP]
Affiliations
- PMID: 32653646
- DOI: 10.1016/j.jsb.2020.107575
Abstract
COVID-19 is a respiratory disease caused by the coronavirus SARS-CoV-2. SARS-CoV-2 has many similarities with SARS-CoV. Both viruses rely on a protease called the main protease, or M[SUP]pro[/SUP], for replication. Therefore, inhibiting M[SUP]pro[/SUP] may be a successful strategy for treating COVID-19. Structures are available in the Protein Data Bank of the main proteases of SARS-CoV and SARS-CoV-2 with and without inhibitor N3. Comparing these structures revealed residue interaction network changes associated with N3 inhibition. Comparing network clustering with and without inhibitor N3 identified the formation of a cluster of residues 17, 18, 30-33, 70, 95, 98, 103, 117, 122, and 177 as a network change in both viral proteases when bound to inhibitor N3. Betweenness and stress centrality differences as well as differences in bond energies and relative B-factors when comparing free M[SUP]pro[/SUP] to inhibitor-bound M[SUP]pro[/SUP] identified residues 131, 175, 182, and 185 as possibly conformationally relevant when bound to the inhibitor N3. Taken together, these results provide insight into conformational changes of betacoronavirus M[SUP]pro[/SUP]s when bound to an inhibitor.
Keywords: 2019-CoV; 3CLpro; COVID-19; M(pro); betweenness.