Whole genome sequence analyses of Indonesian isolates SARS‐CoV‐2 variants and their clinical manifestations

https://doi.org/10.22146/ijbiotech.73783

Elnora Listianto Lie(1), Tedi Dwi Fauzi Hermawan(2), Kholis Abdurachim Audah(3*)

(1) Department of Biomedical Engineering, Faculty of Life Sciences and Technology, Swiss German University (SGU), Tangerang 15143, Indonesia
(2) Department of Biomedical Engineering, Faculty of Life Sciences and Technology, Swiss German University (SGU), Tangerang 15143, Indonesia
(3) Department of Biomedical Engineering, Faculty of Life Sciences and Technology, Swiss German University (SGU), Tangerang 15143, Indonesia
(*) Corresponding Author

Abstract


The SARS‐CoV‐2 virus has been the cause of the global pandemic since the end of 2019. Since then, the virus has mutated to create different types of variants with numerous effects on those infected. This has complicated human intervention for prevention. Indonesia was heavily affected by the pandemic, specifically from May to August 2021, and as a country has recorded many distinct isolates. Thus, characterization of the virus strains from Indonesia is important. GISAID, NCBI BLAST, and MAFFT version 7 were used. There were 9,488 isolates in Indonesia as of November 2021, with the majority including the Delta variant. While most of the isolates have mutations common to those from other countries, there are some atypical ones, such as mutation V1264L in the Delta variant that was suspected to play a role in worsening the pandemic. The Delta variant had the most mutations in the spike protein when compared to the Alpha and Beta variants, giving it important roles in infectivity and vigorous entry into cells, with some general clinical manifestations like fever and sore throat; however, the severity of the Delta variant is attributable to its rapid growth. This is why, from May to November 2021 in Indonesia, cases of the Delta variant rocketed, unlike the other variants.


Keywords


Mutation; SARS‐CoV‐2; Sequence alignment; Whole genome sequence; Wild type; Variant



References

Acro Biosystems. 2021. Nucleocapsid protein (D63G, R203M, G215C, D377Y), His Tag. URL https://www.acrobiosystems.com/P4135­SARSCoV­2­Nucleocapsid­protein­%28D63G­R203MG215C­D377Y%29­His­Tag.html.

Aleem A, Akbar Samad AB, Vaqar S. 2021. Emerging Variants of SARS­CoV­2 And Novel Therapeutics Against Coronavirus (COVID­19). Treasure Island (FL): StatPearls Publishing.

Angeletti S, Benvenuto D, Bianchi M, Giovanetti M, Pascarella S, Ciccozzi M. 2020. COVID­2019: The role of the nsp2 and nsp3 in its pathogenesis. J. Med. Virol. 92(6):584–588. doi:10.1002/jmv.25719.

Azad GK, Khan PK. 2021. Variations in Orf3a protein of SARS­CoV­2 alter its structure and function. Biochem. Biophys. Reports 26:100933. doi:10.1016/j.bbrep.2021.100933.

Bakhshandeh B, Jahanafrooz Z, Abbasi A, Goli MB, Sadeghi M, Mottaqi MS, Zamani M. 2021. Mutations in SARS­CoV­2; Consequences in structure, function, and pathogenicity of the virus. Microb. Pathog. 154:104831. doi:10.1016/j.micpath.2021.104831.

Banerjee S, Seal S, Dey R, Mondal KK, Bhattacharjee P. 2021. Mutational spectra of SARS­CoV­2 ORF1ab polyprotein and signature mutations in the United States of America. J. Med. Virol. 93(3):1428–1435. doi:10.1002/jmv.26417.

Banoun H. 2021. Evolution of SARS­CoV­2: Review of Mutations, Role of the Host Immune System. Nephron 145(4):1–12. doi:10.1159/000515417.

Cahyani I, Putro EW, Ridwanuloh AM, Wibowo S, Hariyatun H, Syahputra G, Akbariani G, Utomo AR, Ilyas M, Loose M, Kusharyoto W, Susanti S. 2022. Genome Profiling of SARS­CoV­2 in Indonesia, ASEAN and the Neighbouring East Asian Countries: Features, Challenges and Achievements. Viruses 14(4):778. doi:10.3390/v14040778.

Cascella M, Rajnik M, Cuomo A, Dulebohn SC, Di Napoli R. 2020. Features, Evaluation and Treatment Coronavirus (COVID­19). Treasure Island (FL): StatPearls Publishing. URL https://www.ncbi.nlm.nih.gov/boo ks/NBK554776.

CDC. 2021. Symptoms of COVID­19. URL https://www.cdc.gov/coronavirus/2019­ncov/s ymptoms­testing/symptoms.html. Accessed: 2022 Jul 24.

Cherian S, Potdar V, Jadhav S, Yadav P, Gupta N, Das M, Rakshit P, Singh S, Abraham P, Panda S. 2021. Sars­cov­2 spike mutations, l452r, t478k, e484q and p681r, in the second wave of covid­19 in Maharashtra, India. Microorganisms 9(7):1542. doi:10.3390/microorganisms9071542.

Chohan F, Ishak A, Alderette T, Rad P, Michel G. 2021. Clinical Presentation of a COVID­19 Delta Variant Patient: Case Report and Literature Review. Cureus p. e18603. doi:10.7759/cureus.18603.

Chowdhury S, Bappy MH, Chowdhury S, Chowdhury MS, Chowdhury NS. 2021. Current Review of Delta Variant of SARS­CoV­2. Eur. J. Med. Heal. Sci. 3(6):23–29. doi:10.24018/ejmed.2021.3.6.1120.

Duncan MJ, Shin JS, Abraham SN. 2002. Microbial entry through caveolae: Variations on a theme. Cell. Microbiol. 4(12):783–791. doi:10.1046/j.1462­ 5822.2002.00230.x.

European Centre for Disease Prevention and Control. 2021. SARS­CoV­2 variants of concern as of 3 December 2021. URL https://www.ecdc.europa.eu/en/ covid­19/variants­concern. Accessed: 2021 Dec 6.

Ferreira IA, Kemp SA, Datir R, Saito A, Meng B, Rakshit P, Takaori­Kondo A, Kosugi Y, Uriu K, Kimura I, Shirakawa K, Abdullahi A, Agarwal A, Ozono S, Tokunaga K, Sato K, Gupta RK. 2021. SARSCoV­2 B.1.617 Mutations L452R and E484Q Are Not Synergistic for Antibody Evasion. J. Infect. Dis. 224(6):989–994. doi:10.1093/infdis/jiab368.

Gulland A. 2021. Beta variant: what we know about symptoms, vaccine protection and cases in the UK and France. Telegr. UK. URL https://www.telegraph.co.uk/global­health/scienc e­and­disease/beta­variant­know­symptoms­vaccine ­protection­cases­uk­france/. Accessed: 2022 Aug 4.

Gupta N, Kaur H, Yadav PD, Mukhopadhyay L, Sahay RR, Kumar A, Nyayanit DA, Shete AM, Patil S, Majumdar T, Rana S, Gupta S, Narayan J, Vijay N, Barde P, Nataraj G, Amrutha Kumari B, Kumari MP, Biswas D, Iravane J, Raut S, Dutta S, Devi S, Barua P, Gupta P, Borkakoty B, Kalita D, Dhingra K, Fomda B, Joshi Y, Goyal K, John R, Munivenkatappa A, Dhodapkar R, Pandit P, Devi S, Dudhmal M, Kinariwala D, Khandelwal N, Tiwari YK, Khatri PK, Gupta A, Khatri H, Malhotra B, Nagasundaram M, Dar L, Sheikh N, Shastri J, Aggarwal N, Abraham P. 2021. Clinical characterization and genomic analysis of samples from COVID­19 breakthrough infections during the second wave among the various states of India. Viruses 13(9):1782. doi:10.3390/v13091782.

Guruprasad L. 2021. Human SARS CoV­2 spike protein mutations. Proteins Struct. Funct. Bioinforma. 89(5):569–576. doi:10.1002/prot.26042.

Harvey WT, Carabelli AM, Jackson B, Gupta RK, Thomson EC, Harrison EM, Ludden C, Reeve R, Rambaut A, Peacock SJ, Robertson DL. 2021. SARS­CoV­2 variants, spike mutations and immune escape. Nat. Rev. Microbiol. 19(7):409–424. doi:10.1038/s41579­ 021­00573­0.

Hui EKW, Nayak DP. 2002. Role of G protein and protein kinase signalling in influenza virus budding in MDCK cells. J. Gen. Virol. 83(12):3055–3066. doi:10.1099/0022­1317­83­12­3055.

Hussman JP. 2020. Cellular and Molecular Pathways of COVID­19 and Potential Points of Therapeutic Intervention. Front. Pharmacol. 11:1169. doi:10.3389/fphar.2020.01169.

Jakhmola S, Indari O, Kashyap D, Varshney N, Das A, Manivannan E, Jha HC. 2021. Mutational analysis of structural proteins of SARS­CoV­2. Heliyon 7(3):e06572. doi:10.1016/j.heliyon.2021.e06572.

Kannan SR, Spratt AN, Cohen AR, Naqvi SH, Chand HS, Quinn TP, Lorson CL, Byrareddy SN, Singh K. 2021. Evolutionary analysis of the Delta and Delta Plus variants of the SARS­CoV­2 viruses. J. Autoimmun. 124:102715. doi:10.1016/j.jaut.2021.102715.

Karyono DR, Wicaksana AL. 2020. Current prevalence, characteristics, and comorbidities of patients with COVID­19 in Indonesia. J. Community Empower. Heal. 3(2):77. doi:10.22146/jcoemph.57325.

Khailany RA, Safdar M, Ozaslan M. 2020. Genomic characterization of a novel SARS­CoV­2. Gene Rep. 19:100682. doi:10.1016/j.genrep.2020.100682.

Khateeb J, Li Y, Zhang H. 2021. Emerging SARS­CoV­ 2 variants of concern and potential intervention approaches. Crit. Care 25(1):1–8. doi:10.1186/s13054­ 021­03662­x.

Korber B, Fischer WM, Gnanakaran S, Yoon H, Theiler J, Abfalterer W, Foley B, Giorgi EE, Bhattacharya T, Parker MD, Partridge DG, Evans CM, Freeman TM, de Silva TI, LaBranche CC, Montefiori DC. 2020. Spike mutation pipeline reveals the emergence of a more transmissible form of SARS­CoV­2. bioRxiv 2020.04.29.069054 doi:10.1101/2020.04.29.069054.

Lee Y, Min P, Lee S, Kim SW. 2020. Prevalence and duration of acute loss of smell or taste in COVID­ 19 patients. J. Korean Med. Sci. 35(18):e174. doi:10.3346/JKMS.2020.35.E174.

Li B, Deng A, Li KB, Hu Y, Li Z, Xiong Q, Liu Z, Guo Q, Zou L, Zhang H, Zhang M, Ouyang F, Su J, Su W, Xu J, Lin H, Sun J, Peng J, Jiang H, Lu J. 2021. Viral infection and Transmission in a large well­traced outbreak caused by the Delta SARS­CoV­2 variant. Nat. Commun. 13(1):460. doi:10.1101/2021.07.07.21260122.

Lubinski B, Fernandes MH, Frazier L, Tang T, Daniel S, Diel DG, Jaimes JA, Whittaker GR. 2022. Functional evaluation of the P681H mutation on the proteolytic activation of the SARS­CoV­2 variant B.1.1.7 (Alpha) spike. iScience 25(1):103589. doi:10.1016/j.isci.2021.103589.

Luna­Muschi A, Borges IC, de Faria E, Barboza AS, Maia FL, Leme MD, Guedes AR, Mendes­Correa MC, Kallas EG, Segurado AC, Duarte AJ, Lazari CS, Andrade PS, Sales FC, Claro IM, Sabino EC, Levin AS, Costa SF. 2022. Clinical features of COVID­19 by SARS­CoV­2 Gamma variant: A prospective cohort study of vaccinated and unvaccinated healthcare workers. J. Infect. 84(2):248–288. doi:10.1016/j.jinf.2021.09.005.

Meng B, Kemp SA, Papa G, Datir R, Ferreira IA, Marelli S, Harvey WT, Lytras S, Mohamed A, Gallo G. 2021. Recurrent emergence of SARSCoV­2 spike deletion H69/V70 and its role in the Alpha variant B.1.1.7. Cell Rep. 35(13):109292. doi:10.1016/j.celrep.2021.109292.

Mohammadi M, Shayestehpour M, Mirzaei H. 2021. The impact of spike mutated variants of SARSCoV2 [Alpha, Beta, Gamma, Delta, and Lambda] on the efficacy of subunit recombinant vaccines. Brazilian J. Infect. Dis. 25(4):101606. doi:10.1016/j.bjid.2021.101606.

Motozono C, Toyoda M, Zahradnik J, Ikeda T, Saito A, Tan TS, Ngare I, Nasser H, Kimura I, Uriu K, Kosugi Y, Torii S, Yonekawa A, Shimono N, Nagasaki Y, Minami R, Toya T, Sekiya N, Fukuhara T, Sato K. 2021. An Emerging SARS­CoV­2 Mutant Evades Cellular Immunity and Increases Infectivity. SSRN Electronic Journal doi:10.2139/ssrn.3827372.

Müller JA, Groß R, Conzelmann C, Krüger J, Merle U, Steinhart J, Weil T, Koepke L, Bozzo CP, Read C, Fois G, Eiseler T, Gehrmann J, van Vuuren J, Wessbecher IM, Frick M, Costa IG, Breunig M, Grüner B, Peters L, Schuster M, Liebau S, Seufferlein T, Stenger S, Stenzinger A, MacDonald PE, Kirchhoff F, Sparrer KM, Walther P, Lickert H, Barth TF, Wagner M, Münch J, Heller S, Kleger A. 2021. SARS­CoV­2 infects and replicates in cells of the human endocrine and exocrine pancreas. Nat. Metab. 3(2):149–165. doi:10.1038/s42255­021­00347­1.

Plante J, Plante K, Debbink K, Weaver S, Menachery V. 2021a. The Variant Gambit: COVID’s Next Move. Cell Host Microbe 29(4):508–515. doi:10.1016/j.chom.2021.02.020.

Plante JA, Liu Y, Liu J, Xia H, Johnson BA, Lokugamage KG, Zhang X, Muruato AE, Zou J, Fontes­Garfias CR, Mirchandani D, Scharton D, Bilello JP, Ku Z, An Z, Kalveram B, Freiberg AN, Menachery VD, Xie X, Plante KS, Weaver SC, Shi PY. 2021b. Spike mutation D614G alters SARS­CoV­2 fitness. Nature 592(7852):116–121. doi:10.1038/s41586­020­2895­ 3.

Pulakuntla S, Lokhande KB, Padmavathi P, Pal M, Swamy KV, Sadasivam J, Singh SA, Aramgam SL, Reddy VD. 2021. Mutational analysis in international isolates and drug repurposing against SARS­CoV­2 spike protein: molecular docking and simulation approach. VirusDisease 32(4):1–13. doi:10.1007/s13337­021­00720­4.

Rantam FA, Prakoeswa CRS, Tinduh D, Nugraha J, Susilowati H, Wijaya AY, Puspaningsih NNT, Puspitasari D, Husada D, Kurniati ND, Aryati A. 2021. Characterization of SARS­CoV­2 East Java isolate, Indonesia. F1000Research 10:480. doi:10.12688/f1000research.53137.1.

Rehman S, Mahmood T, Aziz E, Batool R. 2020. Identification of novel mutations in SARS­COV­2 isolates from Turkey. Arch. Virol. 165(12):2937–2944. doi:10.1007/s00705­020­04830­0.

Rosa G, Brandtner D, Mancini P, Veneri C, Bonanno Ferraro G, Bonadonna L, Lucentini L, Suffredini E. 2021. Key SARS­CoV­2 Mutations of Alpha, Gamma, and Eta Variants Detected in Urban Wastewaters in Italy by Long­Read Amplicon Sequencing Based on Nanopore Technology. Water 13(8):2503. doi:10.3390/w13182503.

Suratekar R, Ghosh P, Niesen MJM, Donadio G, Anand P, Soundararajan V, Venkatakrishnan AJ. 2022. High diversity in Delta variant across countries revealed by genomewide analysis of SARSCoV2 beyond the Spike protein. Mol. Syst. Biol. 18(2):e10673. doi:10.15252/msb.202110673.

Syed AM, Taha TY, Tabata T, Chen IP, Ciling A, Khalid MM, Sreekumar B, Chen PY, Hayashi JM, Soczek KM, Ott M, Doudna JA. 2021. Rapid assessment of SARS­CoV­2–evolved variants using virus­like particles. Science 374(6575):1626– 1632. doi:10.1126/science.abl6184.

Tada T, Zhou H, Dcosta BM, Samanovic MI, Mulligan MJ, Landau NR. 2021. The Spike Proteins of SARSCoV­2 B.1.617 and B.1.618 Variants Identified in India Provide Partial Resistance to Vaccine­elicited and Therapeutic Monoclonal Antibodies. bioRxiv .

The Franciscan Missionaries of Our Lady Health Systeml. 2021. Alpha Variant vs. Delta Variant – How Are the Symptoms Different? URL https: //health.fmolhs.org/body/covid­19/alpha­variant­vs ­delta­variant­how­are­the­symptoms­different/.

Theoharides TC, Conti P. 2021. Be aware of SARS­CoV­ 2 spike protein: There is more than meets the eye. J. Biol. Regul. Homeost. Agents 35(3):833–838.

Tian F, Tong B, Sun L, Shi S, Zheng B, Wang Z, Dong X, Zheng P. 2021. N501y mutation of spike protein in SARS­CoV­2 strengthens its binding to receptor ACE2. Elife 10:e69091. doi:10.7554/eLife.69091.

Ulfah M, Helianti I. 2021. Bioinformatic analysis of the whole genome sequences of SARS­CoV­2 from Indonesia. Iran J. Microbiol. 13(2):145–155. doi:10.18502/ijm.v13i2.5973.

Vassallo M, Manni S, Klotz C, Fabre R, Pini P, Blanchouin E, Sindt A, Lotte L, Dubertrand JM, Liguori S, Berkane N, Duval Y, Rolland F, Pradier C. 2021. Patients admitted for variant alpha COVID­19 have poorer outcomes than those infected with the old strain. J. Clin. Med. 10(16):3550. doi:10.3390/jcm10163550.

Wruck W, Adjaye J. 2021. Detailed phylogenetic analysis tracks transmission of distinct SARS­COV­2 variants from China and Europe to West Africa. Sci. Rep. 11(1):21108. doi:10.1038/s41598­021­00267­w.

Yang XJ. 2021a. Delta­1 variant of SARS­COV­2 acquires spike V1264L and drives the pandemic in Indonesia, Singapore and Malaysia. Res. Sq. PREPRINT(Version 1). doi:10.21203/rs.3.rs­ 999390/v1.

Yang XJ. 2021b. SARS­COV­2 δ variant drives the pandemic in India and Europe via two subvariants. medRxiv doi:10.1101/2021.10.16.21265096.

Yin C. 2020. Genotyping coronavirus SARS­CoV­2: methods and implications. Genomics 112(5):3588– 3596. doi:10.1016/j.ygeno.2020.04.016.

Zahra SA, Iddawela S, Pillai K, Choudhury RY, Harky A. 2020. Can symptoms of anosmia and dysgeusia be diagnostic for COVID­19? Brain Behav. 10(11):e01839. doi:10.1002/brb3.1839.

Zhang J, Zhang J, Tao Z. 2022. Effect of Comorbid Diabetes on Clinical Characteristics of COVID­19 Patients Infected by the Wild­Type or Delta Variant of SARS­CoV­2. Front. Endocrinol. 13:861443. doi:10.3389/fendo.2022.861443.

Zheng YX, Wang L, Kong WS, Chen H, Wang XN, Meng Q, Zhang HN, Guo SJ, Jiang HW, Tao SC. 2021. Nsp2 has the potential to be a drug target revealed by global identification of SARS­CoV­2 Nsp2­interacting proteins. Acta Biochim. Biophys. Sin. (Shanghai). 53(9):1134–1141. doi:10.1093/abbs/gmab088.

Zhou Z, Huang C, Zhou Z, Huang Z, Su L, Kang S, Chen X, Chen Q, He S, Rong X, Xiao F, Chen J, Chen S. 2021. Structural insight reveals SARSCoV­2 ORF7a as an immunomodulating factor for human CD14+ monocytes. iScience 24(3):102187. doi:10.1016/j.isci.2021.102187.



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