Original Article

Bioinformatic analysis of the whole genome sequences of SARS-CoV-2 from Indonesia

Abstract

Background and Objectives: In first May 2020, Indonesia has been successfully submitted the first three full-length sequence of SARS-CoV-2 to GISAID database. Until September 10th, 2020, Indonesia had submitted 54 WGS. In this study, we have analyzed and annotated SARS-CoV-2 mutations in spike protein and main proteases.
Materials and Methods: The Whole Genome Sequence (WGS) of Indonesia were obtained from GISAID data base. The 54 data were taken from March to September 10th, 2020. The sequences corresponded to Spike Protein (SP), 3-chymotrypsin like protease (3CLpro), and papain like protease (PLpro) were selected. The Wuhan genome was used as reference.
Results: In total WGS from Indonesia, we found 5 major clades, which dominated as G clade, where the mutation of D614G was found. This D614G was identified as much as 59%, which mostly reported in late samples submitted. Beside D614G mutation, we report three unique mutations: A352S, S477I, and Q677H. Besides, some mutations were also detected in two domains that were expected to be conserved region, the main viral proteases: PLpro (P77L and V205I), 3CLpro (M49I and L50F).
Conclusion: The analysis of SARS-CoV-2 from WGS Indonesia showed a high genetic variation. The diversity in SARS-CoV-2 may epidemiologically enhance virulence and transmission of this virus. The prevalence of D614G over the time in different locations, indicating that changes in this mutation may related to host infection and the viral transmission. However, some mutations that have been reported in this study were not eligible for the most stable conformation.

1. Begum F, Mukherjee D, Thagriki D, Das S, Tripathi PP, Banerjee AK, et al. Analyses of spike protein from first deposited sequences of SARS-CoV2 from West Bengal, India. bioRxiv 2020. https://doi.org/10.1101/2020.04.28.066985.
2. Zhou P, Yang XL, Wang XG, Chen HD, Chen J, Luo Y, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020;579: 270-273.
3. Forster P, Forster L, Renfrew C, Forster M. Phylogenetic network analysis of SARS-CoV-2 genomes. Proc Natl Acad Sci U S A 2020;117: 9241-9243.
4. Chan JF, Kok KH, Zhu Z, Chu H, To KK, Yuan S, et al. Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with a typical pneumonia after visiting Wuhan. Emerg Microbes Infect 2020;9: 221-236.
5. Yoshimoto FK. The proteins of severe acute respiratory syndrome Coronavirus 2 (SARS CoV 2 or n COV19), the cause of COVID 19. Protein J 2020;39: 198-216.
6. Chitranshi N, Gupta VK, Rajput R, Godinez A, Pushpitha K, Shen T, et al. Evolving geographic diversity in SARS CoV2 and in silico analysis of replicating enzyme 3CLpro targeting repurposed drug candidates. J Transl Med 2020;18: 278.
7. Hoffmann M, Weber HK, Schroeder S, Kruger N, Herrler T, Erichsen S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020;181: 271-280.e8.
8. Wu C, Liu Y, Yang Y, Zhang P, Zhong W, Wang Y, et al. Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods. Acta Pharm Sin B 2020;10: 766-788.
9. Huang Y, Yang C, Xu X, Xu W, Liu S. Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19. Acta Pharmacol Sin 2020;41: 1141-1149.
10. Jaimes JA, André NM, Chappie JS, Millet JK, Whittaker GR. Phylogenetic analysis and structural modeling of SARS-CoV-2 spike protein reveals an evolutionary distinct and proteolytically sensitive activation loop. J Mol Biol 2020;432: 3309-3325.
11. Ou X, Liu Y, Lei X, Li P, Mi Dan, Ren Lili, et al. Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV. Nat Commun 2020;11: 1620.
12. Zhang L, Lin D, Sun X, Curth U, Drosten C, Sauerhering L, et al. Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved a-ketoamide inhibitors. Science 2020;368:409-412.
13. Amamuddy OS, Verkhivker GM, Bishop ÖT. Impact of emerging mutations on the dynamic properties the SARS-CoV-2 main protease: an in silico investigation. bioRxiv 2020. https://doi.org/10.1101/2020.05.29.123190
14. Joshi RS, Jagdale SS, Bansode SB, Shankar SS, Tellis MB, Pandya VK, et al. Discovery of potential multi-target-directed ligands by targeting host-specific SARS-CoV-2 structurally conserved main protease. J Biomol Struct Dyn 2021;39:3099-3114.
15. Bette K, Will MF, Sandrasegaram G, Hyejin Y, James T, Werner A, et al. Spike mutation pipe­line reveals the emergence of a more transmissi­ble form of SARS-CoV-2. bioRxiv 2020. https://doi.org/10.1101/2020.04.29.069054
16. Narendran PK, Prasanta S, Ashwani K. Distribution of the genetic clade “G” of Sars-cov-2 – an insight into COVID-19 virulence and spread in India. IndiaRxiv 2020. https://doi.org/10.35543/osf.io/5fzup
17. Ansori ANM, Kharisma VD, Muttaqin SS, Antonius Y, Parikesit AA. Genetic variant of SARS-CoV-2 isolates in Indonesia: Spike Glycoprotein Gene. J Pure Appl Microbiol 2020;14(suppl 1):971-978.
18. Benvenuto D, Demir AB, Giovanetti M, Bianchi M, Angeletti S, Pascarella S, et al. Evidence for mutations in SARS-CoV-2 Italian isolates potentially affecting virus transmission. J Med Virol 2020;92: 2232-2237.
19. Sallam M, Ababneh NA, Dababseh D, Bakri FG, Mahafzah A. Temporal increase in D614G mutation of SARS-CoV-2 in the Middle East and North Africa: Phylogenetic and mutation analysis study. medRxiv 2020. https://doi.org/10.1101/2020.08.24.20176792
20. Kim JS, Jang JH, Kim JM, Chung YS, Yoo CK, Han MG. Genome-wide identification and characterization of point mutations in the SARS-CoV-2 Genome. Osong Public Health Res Perspect 2020;11: 101-111.
21. Zhang L, Jackson CB, Mou H, Ojha A, Rangarajan ES, Izard T, et al. The D614G mutation in the SARS-CoV-2 spike protein reduces S1 shedding and increases infectivity. bioRxiv 2020. https://doi.10.1101/2020.06.12.148726
22. Eaaswarkhanth M, Al Madhoun A, Al-Mulla F. Could the D614G substitution in the SARS-CoV-2 spike (S) protein be associated with higher COVID-19 mortality? Int J Infect Dis 2020;96: 459-460.
23. Smaoui MR, Yahyaoui H. Unraveling the stability landscape of mutations in the SARS-CoV-2 receptor-binding domain. PREPRINT (Version 1) available at Research Square 2020. https://doi.org/10.21203/rs.3.rs-59058/v1
24. Gao X, Qin B, Chen Pu, Zhu K, Hou P, Wojdyla JA, et al. Crystal structure of SARS-CoV-2 papain-like Protease. Acta Pharm Sin B 2021;11: 237-245.
25. Arya R, Das A, Prashar V, Kumar M. Potential inhibitors against papain-like protease of novel coronavirus (SARS-CoV-2) from FDA approved drugs. chemRxiv 2020. https://doi.org/10.26434/chemrxiv.11860011.v2
26. Yoshino R, Yasuo N, Sekijima M. Identification of key interactions between SARS CoV 2 main protease and inhibitor drug candidates. Sci Rep 2020;10: 12493.
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IssueVol 13 No 2 (2021) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/ijm.v13i2.5973
Keywords
COVID-19; Genetic variation; Indonesia; Mutation; SARS-CoV-2; Spike glycoprotein; Viral proteases
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Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
1.
Ulfah M, Helianti I. Bioinformatic analysis of the whole genome sequences of SARS-CoV-2 from Indonesia. Iran J Microbiol. 2021;13(2):145-155.