Identification of novel mutations in SARS-COV-2 isolates from Turkey

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), originally emerged from Wuhan, has caused an unprecedented worldwide pandemic in the first half of 2020. Since the first report of SARS-CoV-2 on March 10th, 2020 in Turkey, more than 150,000 people in the country have been infected with this virus. In this study, a total of 80 genomic virulent strains from Turkey which were uploaded in NCBI and GISAID database were analyzed with other genomic sequences from different countries with the aim to characterize notable genomic features of SARS-CoV-2 and to identify some novel mutations. Consistent with other studies, the combination of variants at positions C3037T, C14408T and A23403G were most common mutations (73%), that exist together in isolates from Turkey. Our secondary structure prediction analysis also highlighted 11 unique non-substitutional mutations from viral SARS-COV-2 isolates of Turkey in different regions such as in spike (S) protein and non-structural proteins (Nsp2, Nsp3, NSP4, and NSP12/RdRP). Of these 11 mutations, nine of them have been found to be involved in structural alterations at different sites. 3/9 mutants (A771V, T1238I and G1251V) cause alteration in structure of S protein, while the rest of them induces structural changes in Nsp2 (A206T, R207C, T265I), Nsp3 (A1824V), Nsp4 (M2796I) and NSP12 (A4489V). These mutations identified here might have significant functional implications that needs to be addressed for future studies in the context of vaccine engineering and therapeutic interventions. Moreover, transmission and phylogenetic analysis revealed multiple independent sources of introductions for infection of hCovs in Turkey and close phylogenetic relationship of Turkish strains with Saudi strains.

Effect of Genomic and Amino Acid Sequence Mutation on Virulence and Therapeutic Target of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS COV-2)

“…The F106F variant, on the other hand, was causing mutations in the Nsp3 gene. 30,31 Furthermore, ORF1ab regions of the virus from different geographic regions showed mutation of amino acid sequences of encoded proteins. An isolate from China showed N2708S and F2908I, whereas from South Korea and Sweden showed G818S and F4321L.…”

“…47 An RdRp mutation, particularly in position 14408, makes a great contribution to overall increased viral genome mutation rates. There are also reports on the mutation of P323L in RdRp, 13,30 which could resulted in structural rigidity of the protein and consequently lower replication fidelity of RdRp. 31 Lower fidelity of RdRp also leads to higher mutation rates of the virus within host cells, which in turn allows new virulent forms to emerge and influence disease profile.…”

Non-permissive SARS-CoV-2 infection in human neurospheres

“…Our strain has also a mutation in a cofactor of SARS-CoV-2 RNA-dependent RNA polymerase, nsp7, that did not lead to impairments in viral replication in permissive cells such as Vero (Fig 2C), however, this mutation could not be excluded as responsible for the differences observed between the studies. Finally, the T265I nsp2 mutation falls within the extracellular N-terminus of the protein [51] and is thought to cause structural changes, and which can now be found in all geographical locations [52]. Similarly to our work, Zhang and collaborators have also used a strain with increased sensitivity to neutralizing antibodies [53].…”

Epidemiological associations with genomic variation in SARS-CoV-2

“…The 3'-to-5' exonuclease, endoRNAse, 2'-O-Ribose methyltransferase, and spike proteins -roughly from bp 19,000 to 23,000 -show a greater-than-average frequency of mutations. The two peaks of mutation counts in nsp3 (location 3037 C>T) and Spike protein (location 23403 A>G) tend to co-occur 18 .…”