Sequence : Nsp15
Total row(s): 4
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Original Article
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62 mutations identified, including 30 mis-sense mutations, in 22 Moroccan patient isolates showed that Spike_D614G and NSP12_P323L mutations were present in all the analyzed sequences, whereas N_G204R and N_R203K were present in 9 sequences. Link to Clock Diagram depicting Mutation Evolution Rate in Morrocan Isolates,
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 		33558859
(Biosaf Health)
PMID
33558859
Date of Publishing: 2021 Feb 3
Title Genetic diversity and genomic epidemiology of SARS-CoV-2 in Morocco
Author(s) nameBadaoui B, Sadki K et al.
Journal Biosaf Health
Impact factor
- n/a -
Citation count: 7

Most frequent and prevalent mutation reported, with reference to Wuhan sequence (hCoV-19/Wuhan/WIV04/2019), was P323L in the non-structural protein 12 (94.7%) whereas the second frequent mutation was D614G in the Spike glycoprotein region (92.6%), followed by G71S in the non-structural protein 5 (70%). SARS-CoV-2 Genome sequences generated in the study (Refer Supplementary Table 1 and 2)
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 		33359061
(Int J Infect Dis)
PMID
33359061
Date of Publishing: 2020 Dec 21
Title Molecular epidemiology of COVID-19 in Oman: A molecular andsurveillance study for the early transmission of COVID-19 in thecountry
Author(s) nameAl-Mahruqi S, Al-Wahaibi A et al.
Journal Int J Infect Dis
Impact factor
3.42
Citation count: 6

Mutation analysis of 2492 SARS-CoV-2 genomes (belonging to 58 different countries representing six continents and five different climatic zones) revealed 1516 nucleotide variations, 744 amino acid substitutions, and 12 deletion sites. The pattern of mutations was different among the six different continents (Europe, Asia, North America, South America, Africa, and Australia) and five different climatic zones (temperate, tropical, diverse, dry, and continental). Sequences under analysis were retrieved from GISAID database (up to 30 March 2020). NCBI reference strain, Wuhan-Hu-1 (Accession NC_045512) was used as a reference genome for the analysis. Mutation analysis reveals diverse mutation pattern. Importantly, four mutations (Q57H, D614G, L3606F, P4714L) were common to all geographical and climatic conditions.
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 		32814791
(Sci Rep)
PMID
32814791
Date of Publishing: 2020 Aug 19
Title Genome-wide analysis of SARS-CoV-2 virus strains circulating worldwide implicates heterogeneity
Author(s) nameIslam MR, Hoque MN et al.
Journal Sci Rep
Impact factor
4.12
Citation count: 123

Sequence alignment of SARS-CoV-2 Nsp15 with SARS-Co-V, MERS-Co-V, HCoV229E, MHV show that the active site residues are conserved both in terms of sequence and conformation. Structural comparisons suggest that inhibitors of SARS-CoV Nsp15 have good chance to inhibit the SARS-CoV-2 homolog, but inhibitors of MERS-CoV NendoU are unlikely to inhibit the enzyme.
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 		32304108
(Protein Sci)
PMID
32304108
Date of Publishing: 2020 Jul
Title Crystal structure of Nsp15 endoribonuclease NendoU from SARSCoV2
Author(s) nameKim Y, Jedrzejczak R et al.
Journal Protein Sci
Impact factor
2.4
Citation count: 153


Structure : Nsp15
Total row(s): 7
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Original Article
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SARS-CoV-2 Nsp15 is inhibited by interactions with the uridine binding pocket in the enzyme's active site. Structure of SARS CoV-2 Nsp15 endoribonuclease in complex with Uridine-5'-Monophosphate shows Nsp15 discriminates between the uracil and purine bases by forming van der Waals contacts with Tyr343 and hydrogen bonds Ser294 (an active site residue ). Nsp15 enzyme is inhibited by the binding of 5'-UMP in the uracil binding pocket.
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 		33564093
(Commun Biol)
PMID
33564093
Date of Publishing: 2021 Feb 9
Title Tipiracil binds to uridine site and inhibits Nsp15 endoribonuclease NendoU from SARS-CoV-2
Author(s) nameKim Y, Wower J et al.
Journal Commun Biol
Citation count 34
Date of Entry 2021 Aug 2

Structure of SARS-CoV-2 Nsp15 endoribonuclease in complex with 3'-uridine monophosphate shows uracil demonstrates higher affinity for Trp333 site than in uracil-recognition site created by His235, His250, and Thr341. Structure emphasis that since the enzyme's substrate is a larger RNA molecule, the identity of the Trp333-interacting base is inappropriate.
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 		33564093
(Commun Biol)
PMID
33564093
Date of Publishing: 2021 Feb 9
Title Tipiracil binds to uridine site and inhibits Nsp15 endoribonuclease NendoU from SARS-CoV-2
Author(s) nameKim Y, Wower J et al.
Journal Commun Biol
Citation count 34
Date of Entry 2021 Aug 2

Structure of SARS-CoV-2 Nsp15 endoribonuclease in complex with dinucleoside monophosphate (GpU), which binds to the active site of the enzyme with uracil interacting with Tyr343 and Ser294. This results in the SARS-CoV-2 Nsp15 is inhibition. Complex structure demonstrates location and specificity determinants of the uridine with a 5-phosphoryl group. Nsp15 is shown to bind and hydrolyze 4, 7, and 20 nucleotide long RNA. Comparitive study of Nsp15 and RNase A active site displayed some conserved active site residues and indicated a common catalytic mechanism with a two-step reaction releasing 3UMP, despite distinct RNA binding site organization in both including both sequence and structure dissimilarity.
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 		33564093
(Commun Biol)
PMID
33564093
Date of Publishing: 2021 Feb 9
Title Tipiracil binds to uridine site and inhibits Nsp15 endoribonuclease NendoU from SARS-CoV-2
Author(s) nameKim Y, Wower J et al.
Journal Commun Biol
Citation count 34
Date of Entry 2021 Aug 2

The structure of Tipiracil (a uracil derivative ) and SARS-CoV-2 Nsp15 endoribonuclease shows Tipiracil competitively inhibits the enzyme action by binding to its active site. Structure illustrates that uracil alone probably has similar inhibitory properties and provides basis for the uracil scaffold-based drug development.
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 		33564093
(Commun Biol)
PMID
33564093
Date of Publishing: 2021 Feb 9
Title Tipiracil binds to uridine site and inhibits Nsp15 endoribonuclease NendoU from SARS-CoV-2
Author(s) nameKim Y, Wower J et al.
Journal Commun Biol
Citation count 34
Date of Entry 2021 Aug 2

Structure of SARS-CoV-2 Nsp15 endoribonuclease with Uridine-2',3'-Vanadate (UV, a transition state analog), results in the formation of 2′,3′-cyclic phosphodiester. This is critical for further RNA maturation and functions. This structure proposes that Nsp15 should follow a two-step reaction mechanism with the final product being 3UMP.
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 		33564093
(Commun Biol)
PMID
33564093
Date of Publishing: 2021 Feb 9
Title Tipiracil binds to uridine site and inhibits Nsp15 endoribonuclease NendoU from SARS-CoV-2
Author(s) nameKim Y, Wower J et al.
Journal Commun Biol
Citation count 34
Date of Entry 2021 Aug 2

The crystal structure of Nsp15 monomer features three distinct domains:- N‐terminal domain is composed of an antiparallel β‐sheet, middle domain formed by 10 β‐strands and three short helices and C‐terminal catalytic NendoU domain formed by two antiparallel β‐sheets. The structure of SARS‐CoV‐2 Nsp15 monomer is very similar to other Nsp15s from coronaviruses.
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 		32304108
(Protein Sci)
PMID
32304108
Date of Publishing: 2020 Jul
Title Crystal structure of Nsp15 endoribonuclease NendoU from SARSCoV2
Author(s) nameKim Y, Jedrzejczak R et al.
Journal Protein Sci
Impact factor
2.4
Citation count: 153

Citrate ion makes hydrogen bonds with numerous important active site residues, including His235, His250, Lys290, and Thr341, as well as two water molecules and PEG, in the structure of Nsp15/cit at 1.90Å. Structural comparisons suggest that inhibitors of SARS-CoV Nsp15 have good chance to inhibit the SARS-CoV-2 homolog but inhibitors of MERS-CoV NendoU are unlikely to inhibit the enzyme.
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 		32304108
(Protein Sci)
PMID
32304108
Date of Publishing: 2020 Jul
Title Crystal structure of Nsp15 endoribonuclease NendoU from SARSCoV2
Author(s) nameKim Y, Jedrzejczak R et al.
Journal Protein Sci
Impact factor
2.4
Citation count: 153


Drugs : Nsp15
Total row(s): 1
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Original Article
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11,000 compounds out of this library was chosen for target-specific virtual screening based on Lipinskis rule of 5. The natural screening suggested two efficient compounds (PubChem ID: 95372568 and 1776037) with dihydroxyphenyl region of the compound, found to be important in the interaction with the viral protein showing promising activity which may act as a potent lead inhibitory molecule against the virus. In combina tion with virtual screening, modelling, drug like liness, molecular docking, and 500 ns cumulative molecular dynamics simulations (100 ns for each complex) along with the decomposition analysis to calculate and confirm the stability and fold, we propose 95372568 and 1776037 as novel compo unds of natural origin capable of getting develop ed into potent lead molecules against SARS-CoV- 2 target protein NSP15.
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 		33963942
(J Mol Model)
PMID
33963942
Date of Publishing: 2021 May 8
Title Analysis of natural compounds against the activity of SARS-CoV-2 NSP15 protein towards an effective treatment against COVID-19: a theoretical and computational biology approach
Author(s) name Motwalli O, Alazmi M.
Journal J Mol Model
Impact factor
2.9
Citation count: 4
Date of Entry 2021 Sep 5