Coronavirus Genomes and Unique Mutations in Structural and Non-Structural Proteins in Pakistani SARS-CoV-2 Delta Variants during the Fourth Wave of the Pandemic

Abstract

Genomic epidemiology of SARS-CoV-2 is imperative to explore the transmission, evolution, and also pathogenicity of viruses. The emergence of SARS-CoV-2 variants of concern posed a severe threat to the global public health efforts. To assess the potential consequence of these emerging variants on public health, continuous molecular epidemiology is of vital importance. The current study has been designed to investigate the major SARS-CoV-2 variants and emerging mutations in virus structural and non-structural proteins (NSP) during the fourth wave in September 2021 from the Punjab province of Pakistan. Twenty SARS-CoV-2 positive samples have been collected from major cities were subjected to next-generation sequencing. Among the 20 whole genomes (GenBank Accession SRR16294858-SRR16294877), 2 samples failed to be completely sequenced. These genome sequences harbored 207 non-synonymous mutations, among which 19 were unique to GISAID. The genome sequences were detected: Delta 21I, 21J variants (B.1.617.2). Mutation’s spike_F157del, spike_P681R, spike_T478K, spike_T19R, spike_L452R, spike_D614G, spike_G142D, spike_E156G, and spike_R158del have been detected in all samples where K1086Q, E554K, and C1250W were unique in spike protein. These genomic sequences also harbored 129 non-synonymous mutations in NSP. The most common were NSP3_P1469S (N = 17), NSP3_A488S (N = 17), NSP3_P1228L (N = 17), NSP4_V167L (N = 17), NSP4_T492I (N = 17), NSP6_T77A (N = 17), NSP14_A394V (N = 17), NSP12_G671S (N = 18), and NSP13_P77L (N = 18). The mutation, F313Y in NSP12, detected in the current study, was found in a single isolate from Belgium. Numerous other unique mutations have been detected in the virus papain-like protease (NSP3), main protease (NSP5), and RNA-dependent RNA polymerase (NSP12). The most common non-synonymous mutations in the spike protein were subjected to stability analysis, exhibiting a stabilizing effect on structures. The presence of Delta variants may affect therapeutic efforts and vaccine efficacy. Continuous genomic epidemiology of SARS-CoV-2 in Pakistan may be useful for better management of SARS-CoV-2 infections.

Analysis of Whole-Genome Sequencing of SARS-CoV-2 Reveals Recurrent Mutations among Iranian Patients

“…T492I mutation NSP4 protein is highly conserved and increased over time in different continents, especially in recent months [144]. T492I was also found in Pakistani SARS-CoV-2 Variants from 15 to 20 September 2021 [145].…”

“…T492I mutation NSP4 protein is highly conserved and increased over time in different continents, especially in recent months [144]. T492I was also found in Pakistani SARS-CoV-2 Variants from 15 to 20 September 2021 [145]. NSP12 P323L appears in May 2020 and gradually increases and becomes stable in the following months (Figure 7C).…”

Burnout in health care workers during the fourth wave of COVID-19: A cross sectional study from Pakistan

“…In this study, the effect of COVID-19 was critical in 10% of unvaccinated patients [ 4 ]. This is compounded by increasing Delta variants and slow vaccination rate, increasing the burden on HCWs, thus exacerbating stress levels [ 7 ].…”

Containment of SARS-CoV-2 Delta strain in Guangzhou, China by quarantine and social distancing: a modelling study

“…CoV-2 NSP6 inhibits autophagy, which is crucial for viral infections and induces cell death 10 . The mutation NSP6 T77A was commonly identified in Pakistani SARS-CoV-2 Delta variants during the fourth pandemic wave 11 . G671S in NSP12 identified in Delta has been reported to be emerging, increasing the protein's stability and maybe affecting its pathogenicity 11,12 .…”

“…The mutation NSP6 T77A was commonly identified in Pakistani SARS-CoV-2 Delta variants during the fourth pandemic wave 11 . G671S in NSP12 identified in Delta has been reported to be emerging, increasing the protein's stability and maybe affecting its pathogenicity 11,12 . Furthermore, there was no significant difference in the clinical features between Delta and other strains 13 .…”