SARS-CoV-2 Pandemic Tracing in Italy Highlights Lineages with Mutational Burden in Growing Subsets
Abstract
:1. Introduction
2. Results
2.1. Epidemic Trend in Italy during the First Year
2.2. Identification of Growing Virus Subsets in Italy
2.3. Mutational Characterization of Growing Subsets
2.4. Structural Analysis
2.5. Tracing of Variants
3. Discussion
4. Materials and Methods
4.1. Sequence Datasets and Phylodynamic Analysis
4.2. Identification of Growing Virus Subsets
4.3. Detection of Mutated Sites
4.4. Impact of Mutations on Protein Conformation and Stability
4.5. Subset Relationships with Nextstrain Clades/Pango Lineages
4.6. Subset Tracing
- (a)
- full correspondence, if the product is 0.8 or more;
- (b)
- partial correspondence, if the product is less than 0.8, but at least one of the two ratios is more than 0.8;
- (c)
- no relationship, in the other cases.
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Code Availability Statement
Acknowledgments
Conflicts of Interest
References
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Family | Subset | Date | Internal Subsets | # Viral Seqs | Score | Skew | Origin | # Sources | Sex | Clade | Related Pango Lineage | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Italy | Others | Div. | Cent. | F | M | U | Parent | Is | Name | Rel. | |||||||
1 | 4/2020 | 61 | 11.32 | −0.84 | 41 (67%) | 20 (33%) | 6 | 10 | 18 | 31 | 12 | 20A | B.1.258 | ovr | |||
2−3 | 2 | 6/2020 | 47 | 7.21 | −0.68 | 47 (100%) | 0 (0%) | 3 | 5 | 23 | 24 | 0 | 20D | C.18 | not | ||
3 | 4/2020 | 2 | 91 | 14.33 | −0.93 | 56 (62%) | 35 (38%) | 8 | 12 | 34 | 34 | 23 | 20D | B.1.1.1 | par | ||
4 | 10/2020 | 43 | 54.79 | −3.07 | 25 (58%) | 18 (42%) | 6 | 12 | 18 | 16 | 9 | 20B | 20I/501Y.V1 | B.1.1.7 | ovr | ||
5 | 3/2020 | 45 | 6.65 | −0.66 | 4 (9%) | 41 (91%) | 3 | 3 | 7 | 6 | 32 | 20B | B.1.1.39 | ovr | |||
6−7 | 6 | 4/2020 | 31 | 7.77 | −0.77 | 20 (65%) | 11 (35%) | 4 | 7 | 6 | 17 | 8 | 20A.EU2 | B.1.160 | par | ||
7 | 6/2020 | 6 | 164 | 8.66 | −0.56 | 68 (41%) | 96 (59%) | 6 | 12 | 29 | 56 | 79 | 20A | 20A.EU2 | B.1.160 | ovr | |
8 | 6/2020 | 52 | 20.53 | −1.33 | 27 (52%) | 25 (48%) | 5 | 8 | 19 | 13 | 20 | 20E (EU1) | B.1.177 | par | |||
9 | 7/2020 | 33 | 5.81 | −0.66 | 22 (67%) | 11 (33%) | 5 | 6 | 9 | 16 | 8 | 20E (EU1) | B.1.177 | par | |||
10 | 8/2020 | 49 | 13.77 | −1 | 47 (96%) | 2 (4%) | 4 | 5 | 13 | 34 | 2 | 20E (EU1) | B.1.177.33 | not |
Variant | Variant (ORF1ab Peptide) | Nucleotide | Subset | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | |||
5UTR: C241T | - | 241 | C | C | C | C | C | C | C | C | C | C |
ORF1ab: V60V | leader: V60V | 445 | C | C | C | |||||||
ORF1ab: S216S | nsp2: S36S | 913 | B | |||||||||
ORF1ab: F924F | nsp3: F106F | 3037 | C | C | C | C | C | C | C | C | C | C |
ORF1ab: T1001I | nsp3: T183I | 3267 | B | |||||||||
ORF1ab: T1246I | nsp3: T428I | 4002 | C | C | ||||||||
ORF1ab: T1426T | nsp3: T608T | 4543 | C | B | ||||||||
ORF1ab: Y1635Y | nsp3: Y817Y | 5170 | B | |||||||||
ORF1ab: A1708D | nsp3: A890D | 5388 | B | |||||||||
ORF1ab: T1788T | nsp3: T970T | 5629 | C | B | ||||||||
ORF1ab: F1907F | nsp3: F1089F | 5986 | B | |||||||||
ORF1ab: T2007T | nsp3: T1189T | 6286 | C | C | C | |||||||
ORF1ab: I2230T | nsp3: I1412T | 6954 | B | |||||||||
ORF1ab: T2274I | nsp3: T1456I | 7086 | B | |||||||||
ORF1ab: I2501T | nsp3: I1683T | 7767 | B | |||||||||
ORF1ab: Y2594Y | nsp3: Y1776Y | 8047 | B | |||||||||
ORF1ab: S2625S | nsp3: S1807S | 8140 | b | |||||||||
ORF1ab: S2839S | nsp4: S76S | 8782 | ||||||||||
ORF1ab: V2955V | nsp4: V192V | 9130 | B | |||||||||
ORF1ab: M3087I | nsp4: M324I | 9526 | C | B | ||||||||
ORF1ab: G3278S | 3C-like proteinase: G15S | 10,097 | C | C | ||||||||
ORF1ab: F3329F | 3C-like proteinase: F66F | 10,252 | B | b | ||||||||
ORF1ab: A3623S | nsp6: A54S | 11,132 | B | |||||||||
ORF1ab: S3675- | nsp6: S106- | 11,288–11,290 | B | |||||||||
ORF1ab: G3676- | nsp6: G107- | 11,291–11,293 | B | |||||||||
ORF1ab: F3677- | nsp6: F108- | 11,294–11,296 | B | |||||||||
ORF1ab: Y3744Y | nsp6: Y175Y | 11,497 | C | C | ||||||||
ORF1ab: D3897D | nsp7: D38D | 11,956 | B | b | ||||||||
ORF1ab: Y4424Y | RdRp: Y32Y | 13,536 | C | C | ||||||||
ORF1ab: A4577S | RdRp: A185S | 13,993 | C | B | ||||||||
ORF1ab: P4715L | RdRp: P323L | 14,408 | C | C | C | C | C | C | C | C | C | C |
ORF1ab: P4804P | RdRp: P412P | 14,676 | B | |||||||||
ORF1ab: H5005H | RdRp: H613H | 15,279 | B | |||||||||
ORF1ab: V5168L | RdRp: V776L | 15,766 | C | B | ||||||||
ORF1ab: L5283L | RdRp: L891L | 16,111 | b | |||||||||
ORF1ab: T5304T | RdRp: T912T | 16,176 | B | |||||||||
ORF1ab: K5542R | helicase: K218R | 16,889 | C | B | ||||||||
ORF1ab: E5585D | helicase: E261D | 17,019 | C | B | ||||||||
ORF1ab: H5614Y | helicase: H290Y | 17,104 | B | |||||||||
ORF1ab: K5784R | helicase: K460R | 17,615 | B | |||||||||
ORF1ab: L6205L | 3′-to-5′ exon.: L280L | 18,877 | C | B | ||||||||
ORF1ab: L6668L | endoRNAse: L216L | 20,268 | B | |||||||||
ORF1ab: K6958K | 2′-o-MT: K160K | 21,138 | B | b | ||||||||
ORF1ab: S6964A | 2′-o-MT: S166A | 21,154 | B | b | ||||||||
ORF1ab: A6997A | 2′-o-MT: A199A | 21,255 | C | C | C | |||||||
S: H69- | - | 21,767–21,769 | B | |||||||||
S: V70- | - | 21,770 | B | |||||||||
S: Y144- | - | 21,992–21,993 | B | |||||||||
S: A222V | - | 22,227 | C | C | C | |||||||
S: N439K | - | 22,879 | B | |||||||||
S: S477N | - | 22,992 | C | B | ||||||||
S: N501Y | - | 23,063 | B | |||||||||
S: A570D | - | 23,271 | B | |||||||||
S: D614G | - | 23,403 | C | C | C | C | C | C | C | C | C | C |
S: G639S | - | 23,477 | B | |||||||||
S: Q675H | - | 23,587 | b | |||||||||
S: P681H | - | 23,604 | B | |||||||||
S: T716I | - | 23,709 | B | |||||||||
S: T723T | - | 23,731 | C | C | ||||||||
S: S982A | - | 24,506 | B | |||||||||
S: D1118H | - | 24,914 | B | |||||||||
ORF3a: Q57H | - | 25,563 | C | B | ||||||||
ORF3a: L106L | - | 25,710 | C | B | ||||||||
M: Y71Y | - | 26,735 | C | B | ||||||||
M: L93L | - | 26,801 | C | C | C | |||||||
M: I118I | - | 26,876 | C | B | ||||||||
ORF6: L40L | - | 27,319 | B | |||||||||
ORF7b: A15A | - | 27,800 | B | |||||||||
ORF8: H17H | - | 27,944 | B | |||||||||
ORF8: Q27 * | - | 27,972 | B | |||||||||
ORF8: P30L | - | 27,982 | b | |||||||||
ORF8: R52I | - | 28,048 | B | |||||||||
ORF8: Y73C | - | 28,111 | B | |||||||||
N: D3L | - | 28,280–28,282 | B | |||||||||
N: V72I | - | 28,487 | B | |||||||||
N: P199S | - | 28,868 | B | |||||||||
N: R203K | - | 28,881–28,882 | C | C | C | C | ||||||
N: G204R | - | 28,883 | C | C | C | C | ||||||
N: A220V | - | 28,932 | C | C | C | |||||||
N: M234I | - | 28,975 | C | B | ||||||||
N: S235F | - | 28,977 | B | |||||||||
N: P365S | - | 29,366 | B | |||||||||
N: A376T | - | 29,399 | C | B | ||||||||
ORF10: V30L | - | 29,645 | C | C | C | |||||||
3UTR: G32T | - | 29,706 | b | |||||||||
3UTR: G60C | - | 29,734 | B |
Gene | Protein/Peptide | Nucleotide | AA Change | Interactions | Stability (ΔΔG) | Structure | |
---|---|---|---|---|---|---|---|
S1 | ORF1ab | nsp3 | 7767 | I1683T | Decreased hydrophobic interactions to V1678, L1685 | I-Tasser model | |
helicase | 17,104 | H290Y | Hbond to peptide bond of E261. Stacking with F262 | Stabilizing ++ (+2.790 kcal/mol) | 5RL9 | ||
S | spike | 22,879 | N439K | ||||
S2–3 | ORF1ab | 2’-o-ribose methyl transferase | 21,154 | S166A | Hydrophobic interactions to L59 and L126 (H bond to N210 abolished) | Stabilizing + (+0.425 kcal/mol) | 6W75 |
S4 | ORF1ab | nsp3 | 3267 | T183I | Remove a OH group. No polar interaction to Q185 or Q180. | I-Tasser model | |
5388 | A890D | No specific interaction. At the N-terminal of an a-helix | |||||
6954 | I1412T | Smaller side chain. No specific interaction | |||||
nsp6 | 11,288–11,290 | S106- | |||||
11,291–11,293 | G107- | ||||||
11,294–11,296 | F108- | ||||||
helicase | 17,615 | K460R | Hbond to Y457 and electrostatic interaction to D458. Contact to F437 | Stabilizing ++ (+1.254 kcal/mol) | 5RL9 | ||
S | spike | 21,767–21,769 | H69- | ||||
21,770 | V70- | ||||||
21,992–21,993 | Y144- | ||||||
23,063 | N501Y | ||||||
23,271 | A570D | ||||||
23,604 | P681H | ||||||
23,709 | T716I | ||||||
24,506 | S982A | Loss of an inter-protomer H-bond between the S982 and T547 side chains D1118H: S2 | |||||
24,914 | D1118H | ||||||
ORF8 | ORF8 | 27,972 | Q27 * | 7JX6 | |||
28,048 | R52I | Solvent exposed. Contact to S54 | |||||
28,111 | Y73C | Solvent exposed | |||||
N | nucleocapside | 28,280–28,282 | D3L | Hydrophobic interactions to V324 | |||
28,977 | S235F | Exposed at the N-terminus of an a-helix | |||||
S5 | N | nucleocapside | 28,487 | V72I | Increases hydrophobic interactions | ||
28,868 | P199S | H-bond to S197 | |||||
S7 | ORF1ab | nsp4 | 9526 | M324I | Hydrophobic interactions to L321, L323 of the opposite helix | I-Tasser model | |
RdRp | 13,993 | A185S | Add H-bond to V182 and N213 peptide bond | 6YYT | |||
15,766 | V776L | Increases hydrophobic interactions to H752, F753 and Y748 | |||||
helicase | 16,889 | K218R | Exposed to the solvent | 5RL9 | |||
17,019 | E261D | Hbond to S259 (H to Y324 and H290 are abolished) | |||||
S | spike | 22,992 | S477N | ||||
ORF3a | ORF3a | 25,563 | Q57H | Contact to His57 from the other subunit. Wall of the central pore. Interacts to Lys61 | Stabilizing ++ (+1.620 kcal/mol) | 6XDC | |
N | nucleocapside | 28,975 | M234I | C-terminal of an a-helix | |||
29,399 | A376T | Potential Hbond to K374 | |||||
S8 | ORF1ab | nsp6 | 11,132 | A3623S | |||
S | spike | 23,587 | Q675H | ||||
ORF8 | ORF8 | 27,982 | P30L | Solvent exposed | Stabilizing ++ (+1.620 kcal/mol) | 7JX6 | |
S10 | ORF1ab | nsp3 | 7086 | T1456I | Exposed in a loop at the C-terminal of an a-helix. Removes polar interaction to N1457 | I-Tasser model | |
S | spike | 23,477 | G639S | ||||
N | nucleocapside | 29,366 | P365S | Exposed in a loop. Increases local flexibility? |
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Boccia, A.; Tufano, R.; Ferrucci, V.; Sepe, L.; Bianchi, M.; Pascarella, S.; Zollo, M.; Paolella, G. SARS-CoV-2 Pandemic Tracing in Italy Highlights Lineages with Mutational Burden in Growing Subsets. Int. J. Mol. Sci. 2022, 23, 4155. https://doi.org/10.3390/ijms23084155
Boccia A, Tufano R, Ferrucci V, Sepe L, Bianchi M, Pascarella S, Zollo M, Paolella G. SARS-CoV-2 Pandemic Tracing in Italy Highlights Lineages with Mutational Burden in Growing Subsets. International Journal of Molecular Sciences. 2022; 23(8):4155. https://doi.org/10.3390/ijms23084155
Chicago/Turabian StyleBoccia, Angelo, Rossella Tufano, Veronica Ferrucci, Leandra Sepe, Martina Bianchi, Stefano Pascarella, Massimo Zollo, and Giovanni Paolella. 2022. "SARS-CoV-2 Pandemic Tracing in Italy Highlights Lineages with Mutational Burden in Growing Subsets" International Journal of Molecular Sciences 23, no. 8: 4155. https://doi.org/10.3390/ijms23084155