Genomic landscape of alpha-variant of SARS-CoV-2 circulated in Pakistan

Fiaz, Nazia; Khalique, Anjum; Saima, Saima; Basheer, Atia

doi:10.1371/journal.pone.0276171

Cited by 5 publications

(7 citation statements)

References 46 publications

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“…However, among all the proteins of BA.2.75 Omicron SARS-CoV-2, Spike protein had the second highest number of mutations (180 missense, 93 silent SNPs, 3 in-frame deletions, 2 in-frame insertions, 2 frameshift deletions, 4 frameshift insertions and 1 stop-gained variant) after NSP3 (Figs 3 & 4 ). The occurrence of second largest number of mutations in Spike protein, after NSP3, is in agreement with the mutations pattern of the previously reported variants of SARS-CoV-2 [ 23 , 24 ]. In the Spike protein, 33 mutations had a prevalence of >80% ( Table 2 ).…”

Section: Resultssupporting

confidence: 91%

“…Out of these mutations, 605 were present in the ORF1ab which transcribes into 16 non-structural proteins (NSPs). However, among theORF1ab proteins, NSP3 had the largest number of missense (207) and silent mutations (165) ( Table 1 , Fig 2 ) which is also common with the mutation pattern of earlier reported variants of SARS-CoV-2 [ 23 ]. The second largest number of mutations, among the NSPs, were found in the NSP2 protein which had 79 missense and 41 silent mutations followed by RdRp protein (57 missense, 60 silent and 1 frameshift deletion) ( Table 1 , Fig 2 ).…”

Section: Resultssupporting

confidence: 61%

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Genomic architecture and evolutionary relationship of BA.2.75: A Centaurus subvariant of Omicron SARS-CoV-2

2023

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In this study, we explored the genomic architecture and phylogenomic relationship of BA.2.75, a subvariant of Omicron SARS-CoV-2. A set of 1468 whole-genome sequences of BA.2.75, submitted by 28 countries worldwide were retrieved from GISAID and used for finding genomic mutations. Moreover, the phylogenetic analysis of BA.2.75 was performed by using 2948 whole-genome sequences of all sub-variants of Omicron along with the Delta variant of SAS-CoV-2. We detected 1885 mutations, which were further grouped into 1025 missense mutations, 740 silent mutations, 72 mutations in non-coding regions, 16 in-frame deletions, 02 in-frame insertions, 8 frameshift deletions, 8 frameshift insertions and 14 stop-gained variants. Additionally, we also found 11 characteristic mutations having a prevalence of 81–99% and were not observed in any of the previously reported variant of SARS-CoV-2. Out of these mutations K147E, W152R, F157L, E210V, V213G, G339H were found in the NTD, and G446S & N460K in the RBD region of the Spike protein, whereas S403L and T11A were present in the NSP3, and E protein respectively. The phylogenetic relationship of this variant revealed that BA.2.75 is descended from the Omicron sub-variant BA.5. This evolutionary relationship suggests that the surge of BA.5 infections can reduce the severity of the infections accredited to BA.2.75. These findings would also improve our knowledge and understanding that how genetic similarities in different variants of SARS-CoV-2 can prime the immune system to fight off the infection caused by one subvariant, after defeating the other.

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Section: Resultssupporting

confidence: 91%

Section: Resultssupporting

confidence: 61%

Genomic architecture and evolutionary relationship of BA.2.75: A Centaurus subvariant of Omicron SARS-CoV-2

2023

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“…Our observation is consistent with a previous study on conservation and mutational analysis of nonstructural genes of SARS-CoV-2, on the basis of geographic distribution byAnand et al, 2021, in which some of the highly mutating positions in NSP3 were reported as "hotspot zones"[26]. In another conservation and phylogenetic analysis by Fiaz et al, 2021, NSP3 was reported as the most variable nonstructural gene[27]. Among our target sequences, a point mutation was observed in NSP3 sequence of a Japanese strain (accession number = OQ504245.1) showing Guanine in place of highly conserved Adenine residues at position 1140.…”

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confidence: 92%

“…The tertiary structures of guide strands of nal 17 siRNA molecules, which passed the validation criteria were modelled and viewed using UCSF Chimera 1.16 (Fig. [21][22][23][24][25][26][27]. The 3D models obtained were further validated using MolProbity server (Additional le 1: Table S8).…”

Section: Secondary Structure Prediction and Minimum Free Energy Deter...mentioning

confidence: 99%

An immunoinformatic approach to design siRNA molecules against SARS-CoV-2 double membrane vesicle formation and accessory genes

Nawaz

Arif

Ahmad

et al. 2023

Preprint

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Background: The corona virus SARS-CoV-2 is the causative agent of recent most global pandemic. Its genome encodes various proteins categorized as non-structural, accessory, and structural proteins. The non-structural proteins, NSP1-16, are located within the ORF1ab. The NSP3, 4, and 6 together are involved in formation of double membrane vesicle (DMV) in host Golgi apparatus. These vesicles provide anchorage to viral replicative complexes, thus assist replication inside the host cell. While the accessory genes coded by ORFs 3a, 3b, 6, 7a, 7b, 8a, 8b, 9b, 9c, and 10 contribute in cell entry, immunoevasion, and pathological progression. Methods: This in silico study is focused on designing sequence specific siRNA molecules as a tool for silencing the non-structural and accessory genes of the virus. The gene sequences of NSP3, 4, and 6 along with ORF3a, 6, 7a, 8, and 10 were retrieved for conservation, phylogenetic, and sequence logo analyses. siRNA candidates were predicted using siDirect 2.0 targeting these genes. The GC content, melting temperatures, and various validation scores were calculated. Secondary structures of the guide strands and siRNA-target duplexes were predicted. Finally, tertiary structures were predicted and subjected to structural validations. Results: This study revealed that NSP3, 4, and 6 and accessory genes ORF3a, 6, 7a, 8, and 10 have high levels of conservation across globally circulating SARS-CoV-2 strains. A total of 71 siRNA molecules were predicted against the selected genes. Following rigorous screening including binary validations and minimum free energies, final siRNAs with high therapeutic potential were identified, including 7, 2, and 1 against NSP3, NSP4, and NSP6, as well as 3, 1, 2, and 1 targeting ORF3a, ORF7a, ORF8, and ORF10, respectively. Conclusion: Our novel in silico pipeline integrates effective methods from previous studies to predict and validate siRNA molecules, having the potential to inhibit viral replication pathway in vitro. In total, this study identified 17 highly specific siRNA molecules targeting NSP3, 4, and 6 and accessory genes ORF3a, 7a, 8, and 10 of SARS-CoV-2, which might be used as an additional antiviral treatment option especially in the cases of life-threatening urgencies.

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“…protein, which is a main target of the immune evasion and antibody response(Mengist et al 2021), had the highest frequency of the missense mutations(35),Fiaz et al (2022) also found the highest frequency of missense mutations in the s-protein in the alpha-variant. It was followed by the nucleocapsid, beta-variant population in Pakistan was comparatively less virulent than worldwide population.…”

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confidence: 96%

Genomic characterization and phylogenomic relationship of the beta-variant of SARS- CoV-2 in Pakistan

Fiaz

Khalique

Naveed

et al. 2023

Preprint

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In this research, we performed genomic characterization and phylogenomic relationship of beta-variant circulated in Pakistan, compared to the viral population of the world. A set of 105 full-genome sequence samples of beta-VOC from Pakistan, retrieved from GISAID, and aligned through the online tool MAFFT and subjected to mutations identification through Coronapp web-application. Phylogenetic tree was created by using 800 full-genome sequences of beta-variant from ten countries having the highest Pakistani diaspora resides. We found 389 mutations, out of which 227 were missense mutations, however, NSP3 and spike were found to be the most mutable proteins. Interestingly, some characteristic mutations like T265I, K1655N, K3353R in ORF1a, S84L(ORF8) and del241/243(S) which had 92–99% prevalence globally, were not present in beta-variant of Pakistan. Moreover, N501Y(S), E484K(S), L242(S), and S106(NSP6) mutations which had 86%, 85%, 84%, and 91% prevalence globally were only 52%, 50%, 49%, and 73.3% prevalent in Pakistan. Likewise, S794L (NSP3), G30R (N) and W29L (ORF7b) had a global prevalence of just 12%, 0.4%, and 0.3%, but in Pakistan they were 67%, 67%, and 49%, respectively. The phylogeny results showed that majority of the Pakistani samples were clustered together with samples from South Africa, England, and Saudi Arabia. Our results showed that beta-variant of Pakistani population was substantially different from its global population in terms of its genomic variability. However, phylogeny relationship suggested transmission of this variant to Pakistan from South Africa, England, and Saudi Arabia.

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Genomic landscape of alpha-variant of SARS-CoV-2 circulated in Pakistan

Cited by 5 publications

References 46 publications

Genomic architecture and evolutionary relationship of BA.2.75: A Centaurus subvariant of Omicron SARS-CoV-2

Genomic architecture and evolutionary relationship of BA.2.75: A Centaurus subvariant of Omicron SARS-CoV-2

An immunoinformatic approach to design siRNA molecules against SARS-CoV-2 double membrane vesicle formation and accessory genes

Genomic characterization and phylogenomic relationship of the beta-variant of SARS- CoV-2 in Pakistan

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