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Maximum-likelihood phylogeny of 2213 SARS-CoV-2 genomes (A), and temporal frequencies of I120F (B) and S477N (C) substitutions in Oceania. F120 and N477 are located in the base of the nodes. The presence of N477 is indicated in yellow. Abbreviations: Dec, December; Jan, January, Feb, February, Mar, March; Apr, April; Aug, August; Sep, September; Oct, October. In Figures (B,C), the number of isolates analyzed per month was as follows: Jan = 1, Feb = 3, Mar = 144, Apr = 17, May = 6, June = 18, July = 42, Aug = 46, Sep = 42, and Oct = 37.
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In December 2019, the first cases of the novel severe acute respiratory syndrome corona-virus 2 (SARS-CoV-2) were identified in the city of Wuhan, China. Since then, it has spread worldwide with new mutations being reported. The aim of the present study was to monitor the changes in genetic diversity and track non-synonymous substitutions (dN) that...
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Context 1
... detected F120 with moderate frequency (11.4%, n = 67) in AS (Bangladesh) from April 2020 to July 2020 and again in October 2020, and in a genome from EU (Wales) in September 2020. Meanwhile, N477 emerged in late May (2020-05-27;IC 2020IC -05-08-2020) in OC and it spread throughout this region ( Figure S1 and Figure 6A). A second cluster carrying the S477N substitution that included genomes from EU (France, Netherlands, Norway, Belgium and Denmark; n = 15, 78.95%), ...
Context 2
... second cluster carrying the S477N substitution that included genomes from EU (France, Netherlands, Norway, Belgium and Denmark; n = 15, 78.95%), AF (Tunisia; n = 2, 10.52), AS (Hong Kong; n = 1, 5.26%) and OC (New Zealand; n = 1, 5.26%) ( Figure 6A) was detected during September 2020 and November 2020. The phylogenetic trees showed that this cluster corresponded to subclade 20A.EU2 (Figures 4 and 6A). ...
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Over the last decades, the use of phylogenetic methods in the study of emerging infectious diseases has gained considerable traction in public health. Particularly, the integration of phylogenetic analyses with the understanding of the pathogen dynamics at the population level has provided powerful tools for epidemiological surveillance systems. In...
Citations
... The generation of new mutations in a viral population is not favored when the virus is well adap ted to its surroundings since most mutations become harmful due to purifying selection. So, mutations that become more common can either be neutral and fixed by genetic drift or beneficial and fixed by positive selection (128). ...
The spread of SARS-CoV-2 virus accompanied by public availability of abundant sequence data provides a window for the determination of viral evolutionary patterns. In this study, SARS-CoV-2 genome sequences were collected from seven countries in the period January 2020–December 2022. The sequences were classified into three phases, namely, pre-vaccination, post-vaccination, and recent period. Comparison was performed between these phases based on parameters like mutation rates, selection pressure (d N /d S ratio), and transition to transversion ratios (T i /T v ). Similar comparisons were performed among SARS-CoV-2 variants. Statistical significance was tested using Graphpad unpaired t -test. The analysis showed an increase in the percent genomic mutation rates post-vaccination and in recent periods across all countries from the pre-vaccination sequences. Mutation rates were highest in NSP3, S, N, and NSP12b before and increased further after vaccination. NSP4 showed the largest change in mutation rates after vaccination. The d N /d S ratios showed purifying selection that shifted toward neutral selection after vaccination. N, ORF8, ORF3a, and ORF10 were under highest positive selection before vaccination. Shift toward neutral selection was driven by E, NSP3, and ORF7a in the after vaccination set. In recent sequences, the largest d N /d S change was observed in E, NSP1, and NSP13. The T i /T v ratios decreased with time. C→U and G→U were the most frequent transitions and transversions. However, U→G was the most frequent transversion in recent period. The Omicron variant had the highest genomic mutation rates, while Delta showed the highest d N /d S ratio. Protein-wise d N /d S ratio was also seen to vary across the different variants.
IMPORTANCE
To the best of our knowledge, there exists no other large-scale study of the genomic and protein-wise mutation patterns during the time course of evolution in different countries. Analyzing the SARS-CoV-2 evolutionary patterns in view of the varying spatial, temporal, and biological signals is important for diagnostics, therapeutics, and pharmacovigilance of SARS-CoV-2.
... Moderate mutation rates of 9.06×10 7 subs/site/cycle for SARS-CoV and 2.5×10 6 cycle for the mouse hepatitis virus have been observed, both below the predicted range for RNA viruses. Because of its 3'-5' exonuclease (ExoN) activity, this is compatible with NSP 14 playing a role in RNA proofreading or repair [7]. CoV RNA has a big genome, which means that deletions and recombination events may occur, which could allow the virus to adapt to new host conditions, as is the case when a species jumps from one host to another [8]. ...
The current review provides an overview of SARS-CoV-2 variants and mutations that are of interest. The SARS-CoV-2 pandemic has affected the whole world at a significant influence on all levels. Variants of concern (VOC) of SARS-CoV-2 are more transmissible, with the potential to increase infection severity and reduce vaccination efficacy. To date, seven varieties of concern (VOCs) have emerged from the evolution of the SARS-CoV-2 virus during the COVID-19 pandemic: Alpha, Beta, Gamma, Delta, Lambda, Omicron and Mu. In relation to VOCs, there is strong agreement that developing a more effective COVID-19 vaccine is the most important way to push the COVID-19 pandemic to endemic phase. The rapid development of vaccine candidates and beginning of vaccination trials is the consequence of an extraordinary scientific effort and worldwide collaboration. Apart from the vaccination as a preventive measure, several antibodies are being tested or developed as treatment options for COVID-19. But it is important to anticipate whether the new emerging VOCs will remain receptive to antibody therapy or vaccines when they emerge. There is a possible expectation that the worldwide immunization campaign and treatment options will put the COVID-19 pandemic to an endemic era. However, still there are questions regarding what kind of long-term effects the virus and its VOCs will have on humans. Pockets of susceptible individuals and waning immunity after infection or vaccination and recovery, changes in the virus through antigenic drift that decreases the protection, and re-entries from zoonotic reservoirs may all contribute to COVID-19 persistence as an endemic virus, possibly with seasonal epidemic peaks.
... Previous studies found that the S and RdRp gene areas in the genome have the highest mutation rates [41][42][43]. Based on the analysis of the mutations in our study, all Delta sequences had P323L and G671S mutations in the nsp12/RdRp as well as D614G in the Spike. ...
Introduction:
This study aimed to perform mutation and phylogenetic analyses of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Delta variants and analyze the characteristic signs and symptoms of patients infected with SARS-CoV-2 Delta variant originated from Makassar during the Delta outbreak.Methods: We collected samples from patients who were infected with coronavirus disease 2019 (COVID-19) between June and October 2021. We selected the Quantitative Reverse Transcription-Polymerase Chain Reaction (PCR)-positive samples with a cycle threshold value of <30 for whole genome sequencing. Total viral ribonucleic acid (RNA) was isolated from 34 PCR-positive nasopharyngeal swab samples, and whole genome sequencing was performed using the Oxford Nanopore GridlON sequencer. Phylogenetic and maximum clade credibility analyses were performed using the Bayesian Markov chain Monte Carlo method.
Results:
It was found that 33 patients were infected with the SARS-CoV-2 Delta variant in this cohort study, among whom 63.6% (21) patients were female. According to the clinical data, 24 (72.7%), 7 (21.2%), and 2 (6.1%) patients had mild, moderate, and severe COVID-19 infections. Phylogenetic analysis based on the spike and RNA-dependent RNA polymerase (RdRp) genes showed that the collected samples were clustered in the main lineage of B.1.617.2 (Delta variant). The Delta variants had a high frequency of distinct mutations in the spike protein region, including T19R (94.12%), L452R (88.23%), T478K (91.17%), D614G (97%), P681R (97%), and D950 N (97%). Other unique mutations found in a smaller frequency in our samples were present in the N-terminal domain, including A27T (2.94%) and A222V (14.70%), and in the receptor-binding domain, including Q414K (5.88%), G446V (2.94%), and T470 N (2.94%).
Conclusion:
This study revealed the unique mutations in the S protein region of Delta variants. T19R, L452R, T478K/T478R, D614G, P681R, and D950 N were the most common substitutions in Makassar's Delta variant.
... As a result, SARS-CoV-2 is less likely to undergo mutational changes, such as antigenic drift and antigenic shift, which change the virus's genetic makeup and affects how infectious, transmissible and pathogenic is. However, over 3000 distinct point mutations have been found in virus isolates from around the world, indicating an increased frequency of alterations in the SARS-CoV-2 genome during the pandemic (38). Several SARS-CoV-2 genes, including S, N, and nsp12 (RdRP), have a wide mutational range (6). ...
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a persistent negative impact on both the public health and the global economy. To comprehend the origin, transmission routes and discover the mutations that alter the virus’s transmissibility and pathogenicity, full-length SARS-CoV-2 genomes have to be molecularly characterized. Focusing on a two-year time frame (2020-2021), we provide an in-depth virologic and epidemiological overview of the SARS-CoV-2 pandemic in the Republic of North Macedonia by assessing the frequency and distribution of the circulating SARS-CoV-2 variants. Using genetic characterization and phylogenetic analysis we shed light on the molecular evolution of the virus as well as test for a possible connection between specific SARS-CoV-2 haplotypes and the severity of the clinical symptoms. Our results show that one fifth (21.51%) of the tested respiratory samples for SARS-CoV-2 were positive. A noticeable trend in the incidence and severity of the COVID-19 infections was observed in the 60+ age group between males and females. Of the total number of positive cases, the highest incidence of SARS-CoV-2 was noticed in 60+ males (4,170.4/100,000), with a statistically significant (0,0001) difference between the two sexes. Additionally, a 1.8x increase in male mortality and consequentially significantly higher number of death cases was observed compared to females of the same age group (0.001). A total of 327 samples were sequenced in the period March 2020 - August 2021, showing the temporal distribution of SARS-CoV-2 variants circulating in North Macedonia. The phylogenetic analysis showed that most of the viral genomes were closely related and clustered in four distinctive lineages, B.1, B.1.1.7, B.1.351 and B.1.617.2. A statistically significant difference was observed in the 2C_1 haplotype (p=0.0013), where 10.5% of the patients were hospitalized due to severe clinical condition. By employing genetic sequencing, coupled with epidemiological investigations, we investigated viral distribution patterns, identified emerging variants and detected vaccine breakthrough infections. The present work is the first molecular study giving a comprehensive overview of the genetic landscape of circulating SARS-CoV-2 viruses in North Macedonia in a period of two years.
... The newly identified CCoV-Hupn-2018 is another warning sign, for which research should focus on the mechanisms of recombination among CoVs, in addition to the variants that arise as mutation events. The recombination observed over the years among CCoVs are examples of the evolutionary mechanisms of these viruses and continuous, and constant monitoring of these viruses is required [7,8,22]. ...
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), emerged in Wuhan city (Hubei province, China) in December 2019, and the World Health Organization (WHO) declared an international public health emergency on 11 March 2020 [...]
... variant. [147][148][149] The presumed explanation is that mutations interfere with the interaction between Nsp2 and host proteins, 141 ultimately affecting virulence. The immunogenicity of Nsp2 can be applied to the development of inactive or live attenuated virus vaccine. ...
Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the causative agent of the pandemic disease COVID-19, which is so far without efficacious treatment. The discovery of therapy reagents for treating COVID-19 are urgently needed, and the structures of the potential drug-target proteins in the viral life cycle are particularly important. SARS-CoV-2, a member of the Orthocoronavirinae subfamily containing the largest RNA genome, encodes 29 proteins including nonstructural, structural and accessory proteins which are involved in viral adsorption, entry and uncoating, nucleic acid replication and transcription, assembly and release, etc. These proteins individually act as a partner of the replication machinery or involved in forming the complexes with host cellular factors to participate in the essential physiological activities. This review summarizes the representative structures and typically potential therapy agents that target SARS-CoV-2 or some critical proteins for viral pathogenesis, providing insights into the mechanisms underlying viral infection, prevention of infection, and treatment. Indeed, these studies open the door for COVID therapies, leading to ways to prevent and treat COVID-19, especially, treatment of the disease caused by the viral variants are imperative.
... There are also a good number of studies on the physical structure of the virus, how the virus evolved, and finally, how the virus changes over time. Studies have suggested that the COVID-19 virus presents low genetic diversity but has an increasing trend and several hotspot mutations throughout its genome [78,79]. Studying the virus's physical and protein structure is essential for developing vaccines and therapeutics. ...
Abstract: A good amount of research has evolved just in three years in COVID-19 transmission, mortality, vaccination, and some socioeconomic studies. A few bibliometric reviews have already been performed in the literature, especially on the broad theme of COVID-19, without any particular area such as transmission, mortality, or vaccination. This paper fills this gap by conducting a bibliometric review on COVID-19 transmission as the first of its kind. The main aim of this study was to conduct a bibliometric review of the literature in the area of COVID-19 transmission dynamics. We used bibliometric analysis using descriptive and network analysis methods to review the literature in this area using RStudio, Openrefine, VOSviewer, and Tableau. We reviewed 1103 articles published in 2020–2022. The result identified the top authors, top disciplines, research patterns, and hotspots and gave us clear directions for classifying research topics in this area. New research areas are rapidly emerging in this area, which needs constant observation by researchers to combat this global epidemic.
Keywords: COVID-19; COVID-19 transmission; bibliometric review; public health; infectious diseases
... Phylogenetic clustering has been applied in many virological analyses [11][12][13], as well as early in the COVID-19 pandemic to define putative transmission clusters in SARS-CoV-2 [14][15][16]. However, clustering based solely on genetic variation may not be sufficient to effectively identify meaningful clusters in SARS-CoV-2 where there has been rapid spread of the virus with relatively low genetic diversity [17][18][19], as well as periods of lineage replacement with new VoCs also reducing regional genetic diversity in the virus [20]. Additionally, comprehensive sampling of ongoing transmission within a population can result in multiple clusters that are linked genetically through ancestral samples. ...
Background
The COVID-19 pandemic remains a global public health concern. Advances in sequencing technologies has allowed for high numbers of SARS-CoV-2 whole genome sequence (WGS) data and rapid sharing of sequences through global repositories to enable almost real-time genomic analysis of the pathogen. WGS data has been used previously to group genetically similar viral pathogens to reveal evidence of transmission, including methods that identify distinct clusters on a phylogenetic tree. Identifying clusters of linked cases can aid in the regional surveillance and management of the disease. In this study, we present a novel method for producing stable genomic clusters of SARS-CoV-2 cases, cov2clusters, and compare the accuracy and stability of our approach to previous methods used for phylogenetic clustering using real-world SARS-CoV-2 sequence data obtained from British Columbia, Canada.
Results
We found that cov2clusters produced more stable clusters than previously used phylogenetic clustering methods when adding sequence data through time, mimicking an increase in sequence data through the pandemic. Our method also showed high accuracy when predicting epidemiologically informed clusters from sequence data.
Conclusions
Our new approach allows for the identification of stable clusters of SARS-CoV-2 from WGS data. Producing high-resolution SARS-CoV-2 clusters from sequence data alone can a challenge and, where possible, both genomic and epidemiological data should be used in combination.
... In addition to the D614G mutation in the S glycoprotein (23403A > G), a P314L mutation (14408C > T) in the NSP12/RdRp was detected in all the sequences analysed. This finding agrees with previous research which reported a high co-occurrence of these mutations around the globe [62][63][64]. The D614G mutation is associated with a high viral load, infectivity, and transmissibility [50] whereas mutations in the RdRp protein results in a dysfunctional enzyme that generates errors during RNA synthesis, increasing the chances of mutations occurring [62,64,65]. ...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern
(VOCs) have significantly impacted the global epidemiology of the pandemic. From December 2020 to April 2022, we conducted genomic surveillance of SARS-CoV-2 in the Southern Province of Zambia, a region that shares international borders with Botswana, Namibia, and Zimbabwe and is a major tourist destination. Genetic analysis of 40 SARS-CoV-2 whole genomes revealed the circulation of Alpha (B.1.1.7), Beta (B.1.351), Delta (AY.116), and multiple Omicron subvariants with the BA.1 subvariant being predominant. Whereas Beta, Delta, and Omicron variants were associated with the second, third, and fourth pandemic waves, respectively, the Alpha variant was not associated with any wave in the country. Phylogenetic analysis showed evidence of local transmission and possible multiple introductions of SARS-CoV-2 VOCs in Zambia from different European and
African countries. Across the 40 genomes analysed, a total of 292 mutations were observed, including 182 missense mutations, 66 synonymous mutations, 23 deletions, 9 insertions, 1 stop codon, and 11 mutations in the non-coding region. This study stresses the need for the continued monitoring of SARS-CoV-2 circulation in Zambia, particularly in strategically positioned regions such as the Southern Province which could be at increased risk of introduction of novel VOCs.
... However, nucleotide diversity tends to increase as virus incidence enhances. 560 Virus mutation over time has culminated in the emergence of SARS-CoV-2 variants, i.e., virus specimens that are genetically different from the main or initial SARS-CoV-2 lineage. These mutations could be phenotypically neutral, with no major impacts on viral biology, or confer advantages to the variants that possess them, improving viral adaptation and fitness. ...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible and virulent human-infecting coronavirus that emerged in late December 2019 in Wuhan, China, causing a respiratory disease called coronavirus disease 2019 (COVID-19), which has massively impacted global public health and caused widespread disruption to daily life. The crisis caused by COVID-19 has mobilized scientists and public health authorities across the world to rapidly improve our knowledge about this devastating disease, shedding light on its management and control, and spawned the development of new countermeasures. Here we provide an overview of the state of the art of knowledge gained in the last 2 years about the virus and COVID-19, including its origin and natural reservoir hosts, viral etiology, epidemiology, modes of transmission, clinical manifestations, pathophysiology, diagnosis, treatment, prevention, emerging variants, and vaccines, highlighting important differences from previously known highly pathogenic coronaviruses. We also discuss selected key discoveries from each topic and underline the gaps of knowledge for future investigations.
