Genomic Diversity Analysis of SARS-CoV-2 and Epidemiological Features of Adaptation of COVID-19 Agent to Human Population (Communication 1)

Objective: to study the evolution of SARS-CoV-2 virus in the process of adapting to human organism during
the current pandemic.

Materials and methods. Database (GISAID) on nucleotide sequences of SARS-CoV-2 virus genome, obtained from clinical samples during the period of late December, 2019–July, 2020. Phylogenetic tree diagram construction was carried out applying BioNumerics v.7.6 software using Maximum parsimony algorithm.

Results and discussion. The most substantial change in the genomes of SARS-CoV-2 virus are associated one-time mutations in ORF1b (P314L) and S (D614G) genes, as a result of which the overwhelming majority of identified isolates of this virus have the stated pair of substitutions to date. Many researches link the substitution in S (D614G) gene to the decreased pathogenicity in the strains that contain it, which may be also explained by enhanced methodology of patient treatment in the course of pandemic. The effect of the mutation in ORF1b (P314L) gene has not yet been investigated. P314L and D614G mutations are closely related and only their combined presence in the genome favored the dissemination of the genovariants of SARS-CoV-2 virus. Analysis of congregated epidemiological data testifies to the fact that the spread of new genovariants may be associated with biological properties facilitating human-to-human transmission. Thereat, associated decrease in lethality may reflect not only advancements in methods of treatment, but possible attenuation of virulent properties. Thus, observed growth in dissemination potential against the background of decrease in virulence is, probably, one of the forms of adaptation of new coronavirus to human population and, apparently, will remain in the future as the integration of SARS-CoV-2 virus into the structure of seasonal ARVI agents.

1. Cui J., Li F., Shi Z.-L. Origin and evolution of pathogenic coronaviruses. Nat. Rev. Microbiol. 2019; 17(3):181–92. DOI: 10.1038/s41579-018-0118-9.

2. Wu F., Zhao S., Yu B., Chen Y.-M., Wang W., Song Z.-G., Hu Y., Tao Z.-W., Tian J.-H., Pei Y.-Y., Yuan M.-L., Zhang Y.-L., Dai F.-H., Liu Y., Wang Q.-M., Zheng J.-J., Xu L., Holmes E.C., Zhang Y.-Z. A new coronavirus associated with human respiratory disease in China. Nature. 2020; 579(7798):265–9. DOI: 10.1038/s41586-020-2008-3.

3. Zhou P., Yang X.-L., Wang X.-G., Hu B., Zhang L., Zhang W., Si H.-R., Zhu Y., Li B., Huang C.-L., Chen H.-D., Chen J., Luo Y., Guo H., Jiang R.-D., Liu M.-Q., Chen Y., Shen X.-R., Wang X., Zheng X.-S., Zhao K., Chen Q.-J., Deng F., Liu L.-L., Yan B., Zhan F.-X., Wang Y.-Y., Xiao G.-F., Shi Z.-L. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020; 579(7798):270–3. DOI: 10.1038/s41586-020-2012-7.

4. Lu R., Zhao X., Li J., Niu P., Yang B., Wu H., Wang W., Song H., Huang B., Zhu N., Bi Y., Ma X., Zhan F., Wang L., Hu T., Zhou H., Hu Z., Zhou W., Zhao L., Chen J., Meng Y., Wang J., Lin Y., Yuan J., Xie Z., Ma J., Liu W.J., Wang D.Y., Xu W., Holmes E.C., Gao G.F., Wu G., Chen W., Shi W., Tan W. Genomic characterization and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. The Lancet. 2020; 395(10224):565–74. DOI: 10.1016/S0140-6736(20)30251-8.

5. Kupferschmidt K. The pandemic virus is slowly mutating. But does it matter? Science. 2020; 369(6501):238–9. DOI: 10.1126/science.369.6501.238.

6. Bhattacharyya Ch., Das Ch., Ghosh A., Singh A.K., Mukherjee S., Majumder P.P., Basu A., Biswas N.K. Global spread of SARS-CoV-2 subtype with spike protein mutation D614G is shaped by human genomic variations that regulate expression of TMPRSS2 and MX1 genes. bioRxiv. 2020.05.04.075911. DOI: 10.1101/2020.05.04.075911.

7. Li X., Wang W., Zhao X., Zai J., Zhao Q., Li Y., Chaillon A. Transmission dynamics and evolutionary history of 2019-nCoV. J. Med. Virol. 2020; 92(5):501–11. DOI: 10.1002/jmv.25701.

8. Benvenuto D., Giovanetti M., Salemi M., Prosperi M., De Flora C., Alcantara L.C.J., Angeletti S., Ciccozzi M. The global spread of 2019-nCoV: a molecular evolutionary analysis. Pathog. Glob. Health. 2020; 114(2):64–7. DOI: 10.1080/20477724.2020.1725339.

9. Van Dorp L., Acman M., Richard D., Shaw L.P., Ford C.E., Ormond L., Owena C.J., Pang J., Tan C.C.S., Boshier F.A.T., Ortiz A.T., Balloux F. Emergence of genomic diversity and recurrent mutations in SARS-CoV-2. Infect. Genet. Evol. 2020; 83:104351. DOI: 10.1016/j.meegid.2020.104351.

10. Zhao Z., Li H., Wu X., Zhong Y., Zhang K., Zhang Ya-P., Boerwinkle E., Fu Y.-X. Moderate mutation rate in the SARS coronavirus genome and its implications. BMC Evol. Biol. 2004; 4:21. DOI: 10.1186/1471-2148-4-21.

11. Mousavizadeh L., Ghasemi S. Genotype and phenotype of COVID-19: Their roles in pathogenesis. J. Microbiol. Immunol. Infect. 2020. DOI: 10.1016/j.jmii.2020.03.022.

12. Ashour H.M., Elkhatib W.F., Rahman Md.M., Elshabrawy H.A. Insights into the Recent 2019 Novel Coronavirus (SARSCoV-2) in Light of Past Human Coronavirus Outbreaks. Pathogens. 2020; 9(3):186. DOI: 10.3390/pathogens9030186.

13. Pachetti M., Marini B., Benedetti F., Giudici F., Mauro E., Storici P., Masciovecchio C., Angeletti S., Ciccozzi M., Gallo R.C., Zella D., Ippodrino R. Emerging SARS-CoV-2 mutation hot spots include a novel RNA-dependent-RNA polymerase variant. J. Transl. Med. 2020; 18:179. DOI: 10.1186/s12967-020-02344-6.

14. Korber B., Fischer W.M., Gnanakaran S., Yoon H., Theiler J., Abfalterer W., Foley B., Giorgi E.E., Bhattacharya T., Parker M.D., Partridge D.G., Evans C.M., de Silva T.I., LaBranche C.C., Montefiori D.C. Spike mutation pipeline reveals the emergence of a more transmissible form of SARS-CoV-2. bioRxiv. DOI: 10.1101/2020.04.29.069054.

15. Ogawa J., Zhu W., Tonnu N., Singer O., Hunter T., Ryan (Firth) A.L., Pao G.M. The D614G mutation in the SARS-CoV2 Spike protein increases infectivity in an ACE2 receptor dependent manner. bioRxiv. DOI: 10.1101/2020.07.21.214932.

16. Chen W.H., Hotez P.J., Bottazzi M.E. Potential for developing a SARS-CoV receptor-binding domain (RBD) recombinant protein as a heterologous human vaccine against coronavirus infectious disease (COVID)-19. Hum. Vaccin. Immunother. 2020; 16(6):1239–42. DOI: 10.1080/21645515.2020.1740560.

17. Wrapp D., Wang N., Corbett K.S., Goldsmith J.A., Hsieh C.-L., Abiona O., Graham B.S., McLellan J.S. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. 2020; 367(6483): 1260–3. DOI: 10.1126/science.abb2507.

18. Walls A.C., Park Y.-J., Tortorici M.A., Wall A., McGuire A.T., Veesler D. Structure, Function, and Antigenicity of the SARSCoV-2 Spike Glycoprotein. Cell. 2020; 181(2):281–292.e6. DOI: 10.1016/j.cell.2020.02.058.