Genetic variability of SARS-CoV-2 drug binding sites

58 α- and β-coronaviruses have protein sequences reviewed in Uniprot

homologues of SARS-CoV-2 proteins were retrieved in 27 out of these 58 coronaviruses

19 putative drug binding sites were mapped on 3D structures of 15 SARS-CoV-2 proteins

the genetic variability of amino-acids lining these binding sites was evaluated

across these 27 coronaviruses

across >15,000 samples from COVID-19 patients

click on tabs in graphics window for druggability and genetic variability analytics of these binding sites
click on images of protein structures for disease relevance, conservation dendograms and interactive 3D documents (download may take 30 seconds)
details: Yazdani et al. bioRxiv 2021

[Druggability score (Dscore) is calculated with SiteMap: JCIM 2009, 49:377-89]

E - transmembrane
domain [PDB: 7k3g]
Druggable: yes
Conservation: <60%

nsp1 [PDB: 7k7p]
Druggable: no

nsp3 macrodomain ADP-ribose
binding site [PDB: 6w02]
Druggable: yes
Conservation: 60-80%

nsp3 PLpro active
site [PDB: 6wx4]
Druggable: maybe
Conservation: <60%

nsp5 Mpro active
site [PDB: 7bqy]
Druggable: yes
Conservation: <60%

nsp9 dimer interface [PDB: 6w9q]
Druggable: yes
Conservation: <60%

nsp12 RdRp active site [PDB: 7bv2]
Druggable: maybe
Conservation: >80%

nsp12 RdRp ectopic site [PDB: 7bv1]
Druggable: yes
Conservation: <60%

nsp12 RdRp NIRAN ADP-bound
site [PDB: 6xez]
Druggable: maybe
Conservation: >80%

nsp13 helicase ATP site [PDB: 6xez]
Druggable: maybe
Conservation: 60-80%

nsp13 helicase central
channel [PDB: 6zls]
Druggable: yes
Conservation: >80%

nsp14 active site [PDB: 5c8s]
Druggable: yes
Conservation: 60-80%

nsp14 ectopic pocket [PDB: 5c8s]
Druggable: yes
Conservation: 60-80%

nsp15 catalytic site [PDB: 5c8s]
Druggable: no
Conservation: 60-80%

nsp16 catalytic site [PDB: 6wvn]
Druggable: yes
Conservation: 60-80%

ORF3a ion channel [PDB: 7kjr]
Druggable: yes
Conservation: <60%

ORF7a [PDB: 6w37]
Druggable: no

ORF8 [PDB: 7jtl]
Druggable: yes
Conservation: <60%

ORF9b [PDB: 6z4u]
Druggable: yes
Conservation: <60%

spike linoleic acid pocket [PDB: 6zb4]
Druggable: yes
Conservation: <60%

This work was conducted by Setayesh Yazdani, Yining Ding, Nicola De Maio, Nick Goldman and Matthieu Schapira at the Structural Genomics Consortium, Toronto and the European Bioinformatics Institute, Cambridge. It was supported by the Natural Sciences and Engineering Research Council of Canada (grant ALLRP 555329-20).