scholarly journals Trends of Mutation Accumulation Across Global SARS-CoV-2 Genomes: Implications for the Evolution of the Novel Coronavirus

Author(s):  
Chayan Roy ◽  
Santi M Mandal ◽  
Suresh K Mondol ◽  
Shriparna Mukherjee ◽  
Wriddhiman Ghosh ◽  
...  

To understand SARS-CoV-2 microevolution, this study explored the genome-wide frequency, gene-wise distribution, and molecular nature of all point-mutations detected across its 71,703 RNA-genomes deposited in the GISAID repository, till 21 August 2020. Globally, nsp1/nsp2/nsp3/ nsp11 and orf7a/orf3a/S were the most mutation-ridden non-structural and structural genes respectively. Phylogeny based on 4,618 spatiotemporally-representative genomes revealed that entities belonging to the early lineages are mostly spread over Asian countries (including India, the biggest hotspot of the pandemic) whereas the recently-derived lineages are more globally distributed. Of the total 16,602 polymorphism-bearing sites in the pan-genome, 11,037 and 4,965 involved transitions and transversions, which in turn were predominated by cytidine-to-uridine and guanosine-to-uridine conversions, respectively. Positive selection of nonsynonymous mutations (dN/dS >1) in most of the structural, but not non-structural, genes indicated that SARS-CoV-2 has already harmonized its replication/transcription machineries with the host’s metabolic system, while it is still redefining virulence/transmissibility strategies at the molecular level.

Author(s):  
Chayan Roy ◽  
Santi M Mandal ◽  
Suresh K Mondol ◽  
Shriparna Mukherjee ◽  
Wriddhiman Ghosh ◽  
...  

The all-pervasiveness and dynamic nature of the COVID-19 pandemic warrants comprehensive and constant surveillance of the numerous mutations that are accumulating in global SARS-CoV-2 genomes and contributing to the microevoution of the various lineages of the novel coronavirus. This would help us gain insights into the evolving pathogenicity of the virus, and thereby improvise our control and therapeutic strategies. This study explores the genome-wide frequency, gene-wise distribution, and molecular nature, of the large repertoire of point mutations detected across the global dataset of 3,608 SARS-CoV-2 RNA-genomes short-listed from a total 5,485 whole genome sequences deposited in GenBank till 4 June 2020 using a download filter that eliminated all incomplete/gapped sequences. Phylogenomic analysis involving all existing SARS-CoV-2 lineages, represented by 3,740 whole genome sequences from human-source (out of a total of 63,894 sequences stored in the GISAID repository, as on 15 July, 2020), illustrated that the two major-lineages of the virus contributed almost equivalently to the pandemic. However, entities belonging to the early lineages are still mostly spread over Asian countries, whereas those affiliated to recently-derived lineages have a relatively more global distribution. Mutation frequency in the SARS-CoV-2 pan genome was found to be 2.27 × 10-5 nucleotide positions mutated per nucleotide analyzed. An overwhelming majority (count: 1797) of the total 2452 instances of single nucleotide substitution detected (in the SARS-CoV-2 pan genome) were found to be transition mutations with cytidine to uridine (CàU) as the most ubiquitous molecular-type (count: 987). Of the 655 instances of transversion detected, the guanosine to uridine (GàU) variant was most widespread (count: 367). All transcribed and untranscribed loci of the pan genome were found to contain mutation(s). nsp3, and S, N and orf3a, were the most point-mutation-ridden non-structural and structural protein-coding genes, respectively, with 435, 300, 171 and 128 total mutations; 349/86, 192/108, 107/64 and 76/52 transitions/transversions; and 189/48, 106/55, 59/42 and 43/31 CàU/GàU substitutions respectively. Potential mechanistic backgrounds were envisaged for the molecular bias of mutations observed in SARS-CoV-2.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Krishnamoorthy Srikanth ◽  
Nam-Young Kim ◽  
WonCheoul Park ◽  
Jae-Min Kim ◽  
Kwon-Do Kim ◽  
...  

Abstract The Jeju horse, indigenous to the Jeju Island in Korea may have originated from Mongolian horses. Adaptations to the local harsh environment have conferred Jeju horse with unique traits such as small-sized body, stocky head, and shorter limbs. These characteristics have not been studied previously at the genomic level. Therefore, we sequenced and compared the genome of 41 horses belonging to 6 breeds. We identified numerous breed-specific non-synonymous SNPs and loss-of-function mutants. Demographic and admixture analyses showed that, though Jeju horse is genetically the closest to the Mongolian breeds, its genetic ancestry is independent of that of the Mongolian breeds. Genome wide selection signature analysis revealed that genes such as LCORL, MSTN, HMGA2, ZFAT, LASP1, PDK4, and ACTN2, were positively selected in the Jeju horse. RNAseq analysis showed that several of these genes were also differentially expressed in Jeju horse compared to Thoroughbred horse. Comparative muscle fiber analysis showed that, the type I muscle fibre content was substantially higher in Jeju horse compared to Thoroughbred horse. Our results provide insights about the selection of complex phenotypic traits in the small-sized Jeju horse and the novel SNPs identified will aid in designing high-density SNP chip for studying other native horse breeds.


Author(s):  
Richard Delahay ◽  
Jose de la Fuente ◽  
Graham Smith ◽  
Khan Sharun ◽  
Emma Snary ◽  
...  

The novel coronavirus SARS-CoV-2 likely emerged from a wildlife source with transmission to humans followed by rapid geographic spread throughout the globe and dramatic impacts on both human health and global economies. Since the onset of the pandemic, there have been several instances of human-to-animal transmission involving companion, farmed and zoo animals, and one instance of infection in a wild mink, with the clear potential for further spread into free-living wildlife. The establishment of reservoirs of infection in wild animals would create significant challenges to infection control in humans and could pose a threat to the welfare and conservation status of wildlife. Herein, we discuss the potential for exposure, maintenance and onward transmission of SARS-CoV-2 in an initial selection of wild and feral species (bats, canids, felids, mustelids, great apes). Targeted surveillance and dynamic risk assessment are important tools for the early detection of infection in wildlife and a means of collating and synthesising emerging information in a rapidly changing situation. Such efforts should be integrated with public health information to provide insights into the potential role of wild mammals in the continuing epidemiology of SARS-CoV-2. This approach should also be adopted to address the wider need to proactively assess threats to human and animal health from other diseases that may emerge from wildlife.


2021 ◽  
Vol 66 (7-8) ◽  
pp. 83-89
Author(s):  
M. A. Litvinova ◽  
N. V. Muravyeva ◽  
B. S. Belov

Currently, the close attention of the medical and international community is still riveted on the novel coronavirus infection, which caused the pandemic in 2020. Understanding the underlying mechanisms of coronavirus disease-2019 (COVID-19) made it possible to move from the empirical selection of therapy, which was observed at the beginning of the pandemic, to the pathogenetically justified prescription of drugs, including glucocorticoids, anticoagulants, as well as some antirheumatic drugs. However, despite the huge amount of scientific and clinical material accumulated over 1.5 years, the interest in this problem does not wane both due to the existence of a number of unresolved issues, and due to the constant emergence of new (often contradictory) data.


Author(s):  
Richard Delahay ◽  
Jose de la Fuente ◽  
Graham Smith ◽  
Khan Sharun ◽  
Emma Snary ◽  
...  

The novel coronavirus SARS-CoV-2 likely emerged from a wildlife source with transmission to humans followed by rapid geographic spread throughout the globe and severe impacts on both human health and the global economy. Since the onset of the pandemic, there have been many instances of human-to-animal transmission involving companion, farmed and zoo animals, and limited evidence for spread into free-living wildlife. The establishment of reservoirs of infection in wild animals would create significant challenges to infection control in humans and could pose a threat to the welfare and conservation status of wildlife. We discuss the potential for exposure, onward transmission and persistence of SARS-CoV-2 in an initial selection of wild mammals (bats, canids, felids, mustelids, great apes, rodents and cervids). Dynamic risk assessment and targeted surveillance are important tools for the early detection of infection in wildlife, and here we describe a framework for collating and synthesising emerging information to inform targeted surveillance for SARS-CoV-2 in wildlife. Surveillance efforts should be integrated with information from public and veterinary health initiatives to provide insights into the potential role of wild mammals in the epidemiology of SARS-CoV-2.


2021 ◽  
Vol 3 (1) ◽  
Author(s):  
R. J. Delahay ◽  
J. de la Fuente ◽  
G. C. Smith ◽  
K. Sharun ◽  
E. L. Snary ◽  
...  

AbstractThe novel coronavirus SARS-CoV-2 likely emerged from a wildlife source with transmission to humans followed by rapid geographic spread throughout the globe and severe impacts on both human health and the global economy. Since the onset of the pandemic, there have been many instances of human-to-animal transmission involving companion, farmed and zoo animals, and limited evidence for spread into free-living wildlife. The establishment of reservoirs of infection in wild animals would create significant challenges to infection control in humans and could pose a threat to the welfare and conservation status of wildlife. We discuss the potential for exposure, onward transmission and persistence of SARS-CoV-2 in an initial selection of wild mammals (bats, canids, felids, mustelids, great apes, rodents and cervids). Dynamic risk assessment and targeted surveillance are important tools for the early detection of infection in wildlife, and here we describe a framework for collating and synthesising emerging information to inform targeted surveillance for SARS-CoV-2 in wildlife. Surveillance efforts should be integrated with information from public and veterinary health initiatives to provide insights into the potential role of wild mammals in the epidemiology of SARS-CoV-2.


Author(s):  
Anindita Banerjee ◽  
Rakesh Sarkar ◽  
Suvrotoa Mitra ◽  
Mahadeb Lo ◽  
Shanta Dutta ◽  
...  

AbstractBackgroundThis is a comprehensive analysis of 46 Indian SARS-CoV-2 genome sequences available from the NCBI and GISAID repository during early 2020. Evolutionary dynamics, gene-specific phylogeny and emergence of the novel co-evolving mutations in nine structural and non-structural genes among circulating SARS-CoV-2 strains in ten states of India have been assessed.Materials and methods46 SARS-CoV-2 nucleotide sequences submitted from India were downloaded from the GISAID (39/46) or from NCBI (7/46) database. Phylogenetic study and analyses of mutation were based on the nine structural and non-structural genes of SARS-CoV-2 strains. Secondary structure of RdRP/NSP12 protein was predicted with respect to the novel A97V mutation.ResultsPhylogenetic analyses revealed the evolution of “genome-type clusters” and adaptive selection of “L” type SARS-CoV-2 strains with genetic closeness to the bat SARS-like coronaviruses than pangolin or MERS-CoVs. With regards to the novel co-evolving mutations, 2 groups are seen to circulate in India at present: the “major group” (52.2%) and the “minor group” (30.4%), harboring four and five co-existing mutations, respectively. The “major group” mutations fall in the A2a clade. All the minor group mutations, except 11083G>T (L37F, NSP6) were unique to the Indian isolates.ConclusionThe study highlights rapidly evolving SARS-CoV-2 virus and co-circulation of multiple clades and sub-clades, driving this pandemic worldwide. This comprehensive study is a potential resource for monitoring the novel mutations in the viral genome, changes in viral pathogenesis, for designing vaccines and other therapeutics.


Author(s):  
Sultan Saghir ◽  
Naif AlGabri ◽  
Mahmoud Alagawany ◽  
Youssef Attia ◽  
Salem Alailay ◽  
...  

In December 2019, the novel coronavirus disease pandemic (COVID-19) that began in China had infected more than 56 million individuals worldwide and accounted for more than 1.344.000 fatalities. With the dawn of this novel coronavirus (SARS-CoV-2), there was a requirement to select potential therapies that might effectively kill the virus, accelerate the recovery, or decrease the case fatality rate. Besides the currently available antiviral medications for HIV and HCV, the chloroquine/hydroxychloroquine (CQ/HCQ) regimen with or without azithromycin has been repurposed in China and was recommended by the National Health Commission, China in mid-February 2020. By this time, the selection of this regimen was based on its efficacy against the previous SARS-CoV-1 virus and its potential to inhibit viral replication of the SARS-CoV-2 in vitro. There was a shortage of robust clinical proof about the effectiveness of this regimen against the novel SARS-CoV-2. Therefore, extensive research effort has been made by several researchers worldwide to investigate whether this regimen is safe and effective for the management of COVID-19. This review article provides a comprehensive overview of the CQ/HCQ regimen. It summarizes the evaluating data from in vitro studies and clinical studies either for the protection or the treatment against SARS-CoV-2. There is a sharp difference of opinion about the role of CQ/HCQ regimen in treatment of COVID-19. The literature data are controversial and contradictory due to the diverse study design, population selection, dosage, regimen, and outcome measures. Current evidence from the two largest randomized-controlled trials (recovery and solidarity) suggests that the HCQ regimen does not decrease COVID-19 patients’ mortality. However, conflicting data were published from observational studies showing that the drug might be sufficient. Therefore, more investigations are needed to emphasize these findings.


Author(s):  
Richard Delahay ◽  
Jose de la Fuente ◽  
Graham Smith ◽  
Khan Sharun ◽  
Emma Snary ◽  
...  

The novel coronavirus SARS-CoV-2 likely emerged from a wildlife source with transmission to humans followed by rapid geographic spread throughout the globe and dramatic impacts on both human health and global economies. Since the onset of the pandemic, there have been several instances of human-to-animal transmission involving companion, farmed and zoo animals, with the clear potential for spread into free-living wildlife. The establishment of reservoirs of infection in wild animals would create significant challenges to infection control in humans and could pose a threat to the welfare and conservation status of wildlife. Herein, we discuss the potential for exposure, maintenance and onward transmission of SARS-CoV-2 in an initial selection of wild and feral species (bats, canids, felids, mustelids, great apes). Targeted surveillance and dynamic risk assessment are important tools for the early detection of infection in wildlife and a means of collating and synthesising emerging information in a rapidly changing situation. Such efforts should be integrated with public health information to provide insights into the potential role of wild mammals in the continuing epidemiology of SARS-CoV-2. This approach should also be adopted to address the wider need to proactively assess threats to human and animal health from other diseases that may emerge from wildlife.


2021 ◽  
Author(s):  
Shun Nogawa ◽  
Hajime Kanamori ◽  
Koichi Tokuda ◽  
Kaoru Kawafune ◽  
Miyuki Chijiiwa ◽  
...  

The novel coronavirus disease 2019 (COVID-19) pandemic has spread rapidly worldwide. To prevent the spread of COVID-19, mRNA-based vaccines made by Pfizer/BioNTech (BNT162b1) and Moderna (mRNA-1273) have been widely used worldwide, including in Japan. Various adverse events after COVID-19 mRNA vaccinations have been reported, with differences observed among individuals. However, the analysis on the genetic background for susceptibility to side effects has been limited. In the present work, we performed genome-wide association studies (GWAS) for self-reported adverse events of COVID-19 mRNA vaccination in 4,545 Japanese individuals and identified 14 associated loci. Among these, 6p21 was associated with 37.5°C or higher fever, 38 °C or higher fever, and muscle pain. Our results may enable one to prepare for and manage side effects by knowing their susceptibility to the occurrence of adverse events. Furthermore, we obtained valuable data that can lead to the understanding of the mechanism of action of COVID-19 mRNA vaccines.


Sign in / Sign up

Export Citation Format

Share Document