Mutational profile confers increased stability of SARS-CoV-2 spike protein in Brazilian isolates

Abstract

Spike (S) protein has been recognized as a promising molecular target for diagnostic, vaccines and antiviral drugs development for COVID-19. In this study, we analyzed the most predominant mutations in the S protein of Brazilian isolates and predicted the effect of these amino acid alterations to protein conformation. A total of 25,924 sequences were obtained from GISAID for five regions of Brazilian territory (Midwest, North, Northeast, South, and Southeast), according to exclusion criteria. Most of the SARS-CoV-2 isolates belongs to the G clade and showed a large occurrence of D614G, N501Y and L18F substitutions. Prediction effects of these amino acid substitutions on the structure dynamics of the spike protein indicated a positive ΔΔG values and negative ΔΔS_Vib in most cases which is associated to structural stabilization and flexibility reduction of the S protein. Mutations E484K, N501Y and K417N belong to several SARS-CoV-2 variants of concern such as Alpha, Beta, Gamma and Delta, and showed high incidence among Brazilian isolates. These mutations have been described to increase RBD affinity to ACE-2 host and abolishment of RBD affinity to potent neutralizing ant-RBD. The increase in rates of infection and reinfection requires continuous genomic surveillance studies in order to characterize emerging mutations and monitor vaccine efficacy, and thus consideration structural data and dynamics in the observed phenotypes.

Communicated by Ramaswamy H. Sarma

Keywords:

• Structure dynamics
• adaptative evolution
• convergent adaptative evolution
• SARS-CoV-2

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author’s contributions

F.R.S.S., C.R.P., project design. M.S.P.A., M.B., H.H.M.C., D.G.R., G.G., G.M.P.M., B.P.C., handle and management biologicals data. F.R.S.S., D.F.L.N., C.R.P., data, and statistical analysis. F.R.S.S., and C.R.P. wrote the manuscript. All authors (F.R.S.S., S.P.A., M.B., H.H.M.C., D.G.R., G.G., G.M.P.M., B.P.C., D.F.L.N., C.R.P.,) reviewed and edited the manuscript.

Additional information

Funding

This work was supported by grants from National Council for Scientific and Technological Development (CNPq Grant no. 440812/2016-0), Ministry of Health from Brazil, Coordination for the Improvement of Higher Education Personnel (CAPES Grant ID 88881.130804/2016-01) and the São Paulo Research Foundation (FAPESP Grant no. 17/50333-7) to (CRP).