Comprehensive analysis of genomic diversity of SARS-CoV-2 in different geographic regions of India: an endeavour to classify Indian SARS-CoV-2 strains on the basis of co-existing mutations
Abstract:Accumulation of mutations within the genome is the primary driving force in viral evolution within an endemic setting. This inherent feature often leads to altered virulence, infectivity and transmissibility, and antigenic shifts to escape host immunity, which might compromise the efficacy of vaccines and antiviral drugs. Therefore, we carried out a genome-wide analysis of circulating SARS-CoV-2 strains to detect the emergence of novel co-existing mutations and trace their geographical distribution within Indi… Show more
“…A number of convergent findings suggest de-mono-ADP-ribosylation of STAT1 by the SARS-CoV-2NSP3 as a putative cause of the cytokine storm observed in the most severe cases of COVID-19. Also, one deletion (at 28245 bp) was present in 10 samples (AF: 6%) in ORF8, a potentially important gene for viral adaptation to humans 44 Sarkar [ 60 ] Research article India 837 Indian SARS-CoV-2 strains 33 different mutations; 18 of which these were unique to India: S glycoprotein (L54F, K77M, R78M, D294D, E583D, Q677H), NSP3 (G716I, T749I, A994D, D1121G, S1197R), RdRP (A97V, L329I, G571S, V880I), NSP2 (S301F, G339S), and N (S194L) Non-synonymous mutations were found to be 3.07 times more prevalent than synonymous mutations. The A2a clade was found to be dominant in India (71.34%), followed by A3 (23.29%) and B (5.36%), but a heterogeneous distribution was observed among various geographical regions.…”
Introduction
Coronavirus Disease-2019 (SARS-CoV-2) started its devastating trajectory into a global pandemic in Wuhan, China, in December 2019. Ever since, several variants of SARS-CoV-2 have been identified. In the present review, we aimed to characterize the different variants of SARS-CoV-2 and explore the related morbidity and mortality.
Methods
A systematic review including the current evidence related to different variants of SARS-CoV-2 and the related morbidity and mortality was conducted through a systematic search utilizing the keywords in the online databases including Scopus, PubMed, Web of Science, and Science Direct; we retrieved all related papers and reports published in English from December 2019 to September 2020.
Results
A review of identified articles has shown three main genomic variants, including type A, type B, and type C. we also identified three clades including S, V, and G. Studies have demonstrated that the C14408T and A23403G alterations in the Nsp12 and S proteins are the most prominent alterations in the world, leading to life-threatening mutations.The spike D614G amino acid change has become the most common variant since December 2019. From missense mutations found from Gujarat SARS-CoV-2 genomes, C28854T, deleterious mutation in the nucleocapsid (N) gene was significantly associated with patients' mortality. The other significant deleterious variant (G25563T) is found in patients located in Orf3a and has a potential role in viral pathogenesis.
Conclusion
Overall, researchers identified several SARS-CoV-2 variants changing clinical manifestations and increasing the transmissibility, morbidity, and mortality of COVID-19. This should be considered in current practice and interventions to combat the pandemic and prevent related morbidity and mortality.
“…A number of convergent findings suggest de-mono-ADP-ribosylation of STAT1 by the SARS-CoV-2NSP3 as a putative cause of the cytokine storm observed in the most severe cases of COVID-19. Also, one deletion (at 28245 bp) was present in 10 samples (AF: 6%) in ORF8, a potentially important gene for viral adaptation to humans 44 Sarkar [ 60 ] Research article India 837 Indian SARS-CoV-2 strains 33 different mutations; 18 of which these were unique to India: S glycoprotein (L54F, K77M, R78M, D294D, E583D, Q677H), NSP3 (G716I, T749I, A994D, D1121G, S1197R), RdRP (A97V, L329I, G571S, V880I), NSP2 (S301F, G339S), and N (S194L) Non-synonymous mutations were found to be 3.07 times more prevalent than synonymous mutations. The A2a clade was found to be dominant in India (71.34%), followed by A3 (23.29%) and B (5.36%), but a heterogeneous distribution was observed among various geographical regions.…”
Introduction
Coronavirus Disease-2019 (SARS-CoV-2) started its devastating trajectory into a global pandemic in Wuhan, China, in December 2019. Ever since, several variants of SARS-CoV-2 have been identified. In the present review, we aimed to characterize the different variants of SARS-CoV-2 and explore the related morbidity and mortality.
Methods
A systematic review including the current evidence related to different variants of SARS-CoV-2 and the related morbidity and mortality was conducted through a systematic search utilizing the keywords in the online databases including Scopus, PubMed, Web of Science, and Science Direct; we retrieved all related papers and reports published in English from December 2019 to September 2020.
Results
A review of identified articles has shown three main genomic variants, including type A, type B, and type C. we also identified three clades including S, V, and G. Studies have demonstrated that the C14408T and A23403G alterations in the Nsp12 and S proteins are the most prominent alterations in the world, leading to life-threatening mutations.The spike D614G amino acid change has become the most common variant since December 2019. From missense mutations found from Gujarat SARS-CoV-2 genomes, C28854T, deleterious mutation in the nucleocapsid (N) gene was significantly associated with patients' mortality. The other significant deleterious variant (G25563T) is found in patients located in Orf3a and has a potential role in viral pathogenesis.
Conclusion
Overall, researchers identified several SARS-CoV-2 variants changing clinical manifestations and increasing the transmissibility, morbidity, and mortality of COVID-19. This should be considered in current practice and interventions to combat the pandemic and prevent related morbidity and mortality.
“…Notably, the method presented here does not rely on primer specificity as compared to conventional qRT-PCR [72] and therefore any changes in viral genomes (mutations or deletion) do not impact the pathogen detection. Previous studies have shown active genetic recombination events in SARS-CoV-2 genomes which may reduce the accuracy of conventional qRT-PCR detection and thus the primers should be precisely chosen to address these challenges [31, 73–75].…”
Section: Discussionmentioning
confidence: 99%
“…Most recently the delta variant (B. 1.617.2) has been identified with a different sequence and increased transmissibility characteristics [31]. The dynamic changes in SARS-CoV-2 virus genome that have occurred over the period of pandemic, paired with the recent implementation of vaccination programs on a global scale that might further impact variant generation suggests that routine whole genome sequencing of coronavirus genome could be implemented as a vital part of ongoing disease control.…”
Background: Non-targeted whole genome sequencing is a powerful tool to comprehensively identify constituents of microbial communities in a sample. There is no need to direct the analysis to any identification before sequencing which can decrease the introduction of bias and false negatives results. It also allows the assessment of genetic aberrations in the genome (e.g., single nucleotide variants, deletions, insertions and copy number variants) including in noncoding protein regions.
Methods: The performance of four different random priming amplification methods to recover RNA viral genetic material of SARS-CoV-2 were compared in this study. In method 1 (H-P) the reverse transcriptase (RT) step was performed with random hexamers whereas in methods 2-4 RT incorporating an octamer primer with a known tag. In methods 1 and 2 (K-P) sequencing was applied on material derived from the RT-PCR step, whereas in methods 3 (SISPA) and 4 (S-P) an additional amplification was incorporated before sequencing.
Results: The SISPA method was the most effective and efficient method for non-targeted/random priming whole genome sequencing of COVID that we tested. The SISPA method described in this study allowed for whole genome assembly of SARS-CoV-2 and influenza A(H1N1)pdm09 in mixed samples. We determined the limit of detection and characterization of SARS-CoV-2 virus which was 103 pfu/ml (Ct, 22.4) for whole genome assembly and 101 pfu/ml (Ct, 30) for metagenomics detection.
Conclusions: The SISPA method is predominantly useful for obtaining genome sequences from RNA viruses or investigating complex clinical samples as no prior sequence information is needed. It might be applied to monitor genomic virus changes, virus evolution and can be used for fast metagenomics detection or to assess the general picture of different pathogens within the sample.
“…For performing mutational analysis, each of the 25 protein coding regions of circulating SARS-CoV-2 genomes as well as prototype genome (hCoV-19/Wuhan/WIV04/2019) was cut and subsequently translated to amino acid sequence by using TRANSEQ nucleotide-to-protein sequence conversion tool (EMBL-EBI, Cambridgeshire, UK). Next, each of the 25 protein sequences of 2000 SARS-CoV-2 genomes was aligned with the corresponding protein sequence of the prototype strain by using MEGA software (Version X) and observed for amino acid substitutions [17]. [18].…”
India is currently facing the devastating second wave of COVID-19 pandemic resulting in approximately 4000 deaths per day. To control this pandemic continuous mutational surveillance and genomic epidemiology of circulating strains is very important. In this study, we performed mutational analysis of the protein coding genes of SARS-CoV-2 strains (n=2000) collected during January 2021 to March 2021. Our data revealed the emergence of a new variant in West Bengal, India, which is characterized by the presence of 11 co-existing mutations including D614G, P681H and V1230L in S-glycoprotein. This new variant was identified in 70 out of 412 sequences submitted from West Bengal. Interestingly, among these 70 sequences, 16 sequences also harbored E484K in the S glycoprotein. Phylogenetic analysis revealed strains of this new variant emerged from GR clade (B.1.1) and formed a new cluster. We propose to name this variant as GRL or lineage B.1.1/S:V1230L due to the presence of V1230L in S glycoprotein along with GR clade specific mutations. Co-occurrence of P681H, previously observed in UK variant, and E484K, previously observed in South African variant and California variant, demonstrates the convergent evolution of SARS-CoV-2 mutation. V1230L, present within the transmembrane domain of S2 subunit of S glycoprotein, has not yet been reported from any country. Substitution of valine with more hydrophobic amino acid leucine at position 1230 of the transmembrane domain, having role in S protein binding to the viral envelope, could strengthen the interaction of S protein with the viral envelope and also increase the deposition of S protein to the viral envelope, and thus positively regulate virus infection. P618H and E484K mutation have already been demonstrated in favor of increased infectivity and immune invasion respectively. Therefore, the new variant having G614G, P618H, P1230L and E484K is expected to have better infectivity, transmissibility and immune invasion characteristics, which may pose additional threat along with B.1.617 in the ongoing COVID-19 pandemic in India.
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