Variations in spike gene of SARS-CoV-2 isolated in Vietnam

Paper Details

Research Paper 06/11/2022
Views (556) Download (84)

Variations in spike gene of SARS-CoV-2 isolated in Vietnam

Quan Ke Thai, Phuoc Huynh, Duc Minh Le
Int. J. Biosci.21( 5), 83-92, November 2022.
Certificate: IJB 2022 [Generate Certificate]


The S gene encodes the spike protein, which plays an important role in the life cycle of SARS-CoV-2. Many mutations in the S gene demonstrate the increase in the transmission rate, helping viral can escape the immune system and monoclonal antibodies. This study aims to track the genetic diversity of the S gene of SARS-CoV-2 isolated in Vietnam during the four waves of the pandemic. A total of 5478 S gene sequences were extracted and classified into 1093 haplotypes, giving the mean number of pairwise differences at 27.491490 ± 12.039763 and the haplotype diversity index at 0.9089 ± 0.0031. In addition, we recorded the nucleotide diversity index at 0.007176 ± 0.003475 with 802 polymorphic sites. We found that indel mutations appear mainly in the NTD coding region, and amino acid substitutions appear most in the RBD coding region. In the RBD region, we also recorded mutations that increase the transmission rate for SARS-CoV-2 with a large proportion in Vietnam: G22578A (G339D), C22686T (S375F), G22813T (K417N), T22917G (L452R), C22995A (T478K) and A23063T (N501Y). In addition, the furin cleavage site also recorded three important mutations in enhancing transmissibility namely A23403G (D614G) and C23604A/G (P681H/R). The mean nucleotide difference between haplotypes in the cluster of Delta variants was 1.989772 ± 1.123948 nucleotides. The Omicron cluster has a tremendous nucleotide difference of 17.951297 ± 7.970441 nucleotides. The analysis results showed the whole picture of variations in the spike gene of SARS-CoV-2 in Vietnam, supporting the management of new variants imported into Vietnam.


Berrio A, Gartner V, Wray GA. 2020. Positive selection within the genomes of SARS-CoV-2 and other Coronaviruses independent of impact on protein function. Peer J 8, e10234.

Bolze A, Luo S, White S, Cirulli ET, Wyman D, Dei Rossi A, Machado H, Cassens T, Jacobs S, Schiabor Barrett KM, Tanudjaja F, Tsan K, Nguyen J, Ramirez J 3rd M, Sandoval E, Wang X, Wong D, Becker D, Laurent M, Lu JT, Isaksson M, Washington NL, Lee W. 2022. SARS-CoV-2 variant Delta rapidly displaced variant Alpha in the United States and led to higher viral loads. Cell Rep Med 3(3), 100564.

Campbell F, Archer B, Laurenson-Schafer H, Jinnai Y, Konings F, Batra N, Pavlin B, Vandemaele K, Van Kerkhove MD, Jombart T, Morgan O, le Polain de Waroux O. 2021. Increased transmissibility and global spread of SARS-CoV-2 variants of concern as at June 2021. Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin 26(24), 2100509.

Chaguza C, Coppi A, Earnest R, Ferguson D, Kerantzas N, Warner F, Young HP, Breban MI, Billig K, Koch RT, Pham K, Kalinich CC, Ott IM, Fauver JR, Hahn AM, Tikhonova IR, Castaldi C, De Kumar B, Pettker CM, Warren JL, Weinberger DM, Landry ML, Peaper DR, Schulz W, Vogels CBF, Grubaugh ND. 2022. Rapid emergence of SARS-CoV-2 Omicron variant is associated with an infection advantage over Delta in vaccinated persons. Med (New York, N.Y.).

Chau NVV, Hong NTT, Ngoc NM, Anh NT, Trieu HT, Nhu LNT, Yen LM, Minh NN, Phong QNT, Truong NT, Huong LTT, Tu TNH, Hung LM, Thanh TT, Dung NT, Dung NT, Thwaites G, Van Tan L, For OCRG. 2021. Rapid whole-genome sequencing to inform COVID-19 outbreak response in Vietnam. The Journal of infection 82(6), 276-316.

Cherian S, Potdar V, Jadhav S, Yadav P. 2021. SARS-CoV-2 Spike Mutations, L452R, T478K, E484Q and P681R, in the Second Wave of COVID-19 in Maharashtra, India.  9(7).

Di Giacomo S, Mercatelli D, Rakhimov A, Giorgi FM. 2021. Preliminary report on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike mutation T478K. Journal of Medical Virology 93(9), 5638-5643.

Durmaz B, Abdulmajed O, Durmaz R. 2020. Mutations Observed in the SARS-CoV-2 Spike Glycoprotein and Their Effects in the Interaction of Virus with ACE-2 Receptor. Medeniyet Medical Journa 35(3), 253-260.

Excoffier L, Lischer HE. 2010. Arlequin suite ver 3.5: a new series of programs to perform population genetics analyses under Linux and Windows. Mol Ecol Resour 10(3), 564-567.

Fan LQ, Hu XY, Chen YY, Peng XL, Fu YH, Zheng YP, Yu JM, He JS. 2021. Biological Significance of the Genomic Variation and Structural Dynamics of SARS-CoV-2 B.1.617. Frontiers in microbiology 12, 750725-750725.

Hoang VT, Pham TD, Nguyen QT, Nguyen DC, Nguyen DT, Nguyen TB, Tran TKT, Phan TL, Vo PLN, Dao TL, Fenollar F, Gautret P. 2022. Seroprevalence of SARS-CoV-2 among high-density communities and hyper-endemicity of COVID-19 in Vietnam. Trop Med Int Health.

Katoh K, Standley DM. 2013. MAFFT Multiple Sequence Alignment Software Version 7: Improvements in Performance and Usability. Molecular Biology and Evolution 30(4), 772-780.

Kumar S, Thambiraja TS, Karuppanan K, Subramaniam G. 2022. Omicron and Delta variant of SARS-CoV-2: A comparative computational study of spike protein. Journal of Medical Virology 94(4), 1641-1649.

Kumar V, Singh J, Hasnain SE, Sundar D. 2021. Possible Link between Higher Transmissibility of Alpha, Kappa and Delta Variants of SARS-CoV-2 and Increased Structural Stability of Its Spike Protein and hACE2 Affinity. International journal of molecular sciences 22(17), 9131.

Leigh JW, Bryant D. 2015. popart: full-feature software for haplotype network construction. Methods in Ecology and Evolution 6(9), 1110-1116.

Liu Y, Liu J, Johnson BA, Xia H, Ku Z, Schindewolf C, Widen SG, An Z, Weaver SC, Menachery VD, Xie X, Shi PY. 2022. Delta spike P681R mutation enhances SARS-CoV-2 fitness over Alpha variant. Cell Reports 39(7), 110829.

Liu Y, Liu J, Plante KS, Plante JA, Xie X, Zhang X, Ku Z, An Z, Scharton D, Schindewolf C, Widen SG, Menachery VD, Shi PY, Weaver SC. 2022. The N501Y spike substitution enhances SARS-CoV-2 infection and transmission. Nature 602(7896), 294-299.

Lubinski B, Fernandes MHV, 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 SARS-CoV-2 variant B.1.1.7 (Alpha) spike. iScience 25(1), 103589.

Lyngse FP, Molbak K, Skov RL, Christiansen LE, Mortensen LH, Albertsen M, Moller CH, Krause TG, Rasmussen M, Michaelsen TY, Voldstedlund M, Fonager J, Steenhard NC. Danish Covid-19 Genome, Kirkeby CT. 2021. Increased transmissibility of SARS-CoV-2 lineage B.1.1.7 by age and viral load. Nat Commun 12(1), 7251.

McCarthy KAO, Rennick LAO, Nambulli SAO, Robinson-McCarthy LAO, Bain WAO, Haidar G, Duprex WAO. Recurrent deletions in the SARS-CoV-2 spike glycoprotein drive antibody escape. (1095-9203 (Electronic)).

Minh LHN, Khoi Quan N, Le TN, Khanh PNQ, Huy NT. 2021. COVID-19 Timeline of Vietnam: Important Milestones Through Four Waves of the Pandemic and Lesson Learned. Front Public Health 9, 709067.

Mishra T, Dalavi R, Joshi G, Kumar A, Pandey P, Shukla S, Mishra RK, Chande A. 2022. SARS-CoV-2 spike E156G/Delta157-158 mutations contribute to increased infectivity and immune escape. Life Sci Alliance 5(7).

O’Toole A, Pybus OG, Abram ME, Kelly EJ. Rambaut A. 2022. Pango lineage designation and assignment using SARS-CoV-2 spike gene nucleotide sequences. BMC Genomics 23(1), 121.

Ovsyannikova IG, Haralambieva IH, Crooke S. N, Poland GA, Kennedy RB. 2020. The role of host genetics in the immune response to SARS-CoV-2 and COVID-19 susceptibility and severity. Immunol Rev 296(1), 205-219.

Rozas J, Ferrer-Mata A, Sánchez-DelBarrio JC, Guirao-Rico S, Librado P, Ramos-Onsins SE, Sánchez-Gracia A. 2017. DnaSP 6: DNA Sequence Polymorphism Analysis of Large Data Sets. Molecular Biology and Evolution 34(12), 3299-3302.

Tamura K, Stecher G, Kumar S. 2021. MEGA11: Molecular Evolutionary Genetics Analysis Version 11. Mol Biol Evol 38(7), 3022-3027.

Venkatakrishnan A, Praveen Anand, Patrick Lenehan, Rohit Suratekar, Bharathwaj Raghunathan, Michiel Niesen J, Venky Soundararajan. 2021. Omicron Variant of Sars-cov-2 Harbors a Unique Insertion Mutation of Putative Viral or Human Genomic Origin. OSF Preprints December 3.

Walker AS, Vihta KD, Gethings O, Pritchard E, Jones J, House T, Bell I, Bell JI, Newton JN, Farrar J, Diamond I, Studley R, Rourke E, Hay J, Hopkins S, Crook D, Peto T, Matthews DW, Eyre N, Stoesser, Pouwels KB. 2021. Tracking the Emergence of SARS-CoV-2 Alpha Variant in the United Kingdom. New England Journal of Medicine 385(27), 2582-2585.

Wei C, Shan KJ, Wang W, Zhang S, Huan Q, Qian W. 2021. Evidence for a mouse origin of the SARS-CoV-2 Omicron variant. J Genet Genomics 48(12), 1111-1121.

Yang J, Han M, Wang L, Wang L, Xu T, Wu L, Ma J, Wong G, Liu W, Gao GF, Bi Y. 2022. Relatively rapid evolution rates of SARS-CoV-2 spike gene at the primary stage of massive vaccination. Biosaf Health 4(4), 228-233.

Yang W, Shaman J. 2022. COVID-19 pandemic dynamics in India, the SARS-CoV-2 Delta variant and implications for vaccination. J R Soc Interface 19(191), 20210900.

Zhang L, Jackson CB, Mou H, Ojha A, Peng H, Quinlan BD, Rangarajan ES, Pan A, Vanderheiden A, Suthar MS, Li W, Izard T, Rader C, Farzan M, Choe H. 2020. SARS-CoV-2 spike-protein D614G mutation increases virion spike density and infectivity. Nature Communications 11(1), 6013.

Zhou H, Yang J, Zhou C, Chen B, Fang H, Chen S, Zhang X, Wang L, Zhang L. 2021. A Review of SARS-CoV2: Compared With SARS-CoV and MERS-CoV. Front Med (Lausanne) 8, 628370.