Mutation Rates, Mutation Frequencies, and Proofreading-Repair Activities in RNA Virus Genetics

Domingo, Esteban; García-Crespo, Carlos; Lobo-Vega, Rebeca; Perales, Celia

doi:10.3390/v13091882

Cited by 99 publications

(89 citation statements)

References 120 publications

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“…A mutation rate of 9.9 × 10–4 to 2.2 × 10–3 nucleotides/genome per year for SARS-CoV-2 has been estimated, according to L. Vázquez-Sirvent, B. Martínez-González, M.E. Soria, and C. Perales, unpublished results, which is similar to other active RNA viruses ( Domingo et al, 2021 ). In this study we described the genetic changes in our SARS-CoV-2 samples.…”

Section: Discussionmentioning

confidence: 60%

Mutation profile of SARS-CoV-2 genome in a sample from the first year of the pandemic in Colombia

Bermúdez¹,

Chaparro-Solano

Pinzón-Rondón

et al. 2022

Infection, Genetics and Evolution

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The severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is the etiopathogenic agent of COVID-19, a condition that has led to a formally recognized pandemic by March 2020 (World Health Organization –WHO). The SARS-CoV-2 genome is constituted of 29,903 base pairs, that code for four structural proteins (N, M, S, and E) and more than 20 non-structural proteins. Mutations in any of these regions, especially in those that encode for the structural proteins, have allowed the identification of diverse lineages around the world, some of them named as Variants of Concern (VOC) and Variants of Interest (VOI), according to the WHO and CDC. In this study, by using Next Generation Sequencing (NGS) technology, we sequenced the SARS-CoV-2 genome of 422 samples from Colombian residents, all of them collected between April 2020 and January 2021. We obtained genetic information from 386 samples, leading us to the identification of 14 new lineages circulating in Colombia, 13 of which were identified for the first time in South America. GH was the predominant GISAID clade in our sample. Most mutations were either missense (53.6%) or synonymous mutations (37.4%), and most genetic changes were located in the ORF1ab gene (63.9%), followed by the S gene (12.9%). In the latter, we identified mutations E484K, L18F, and D614G. Recent evidence suggests that these mutations concede important particularities to the virus, compromising host immunity, the diagnostic test performance, and the effectiveness of some vaccines. Some important lineages containing these mutations are the Alpha, Beta, and Gamma (WHO Label). Further genomic surveillance is important for the understanding of emerging genomic variants and their correlation with disease severity.

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Section: Discussionmentioning

confidence: 60%

Mutation profile of SARS-CoV-2 genome in a sample from the first year of the pandemic in Colombia

Bermúdez¹,

Chaparro-Solano

Pinzón-Rondón

et al. 2022

Infection, Genetics and Evolution

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“…In contrast to most RNA viruses, the large 30,000 nt coronaviruses genome encodes an RNA proofreading 3'-5' exonuclease, by its nsp14, that increases the RNA copy fidelity 13,14 . Ultimately, it maintains genetic stability of the coronavirus genome 15 . RNA viruses with smaller genomes, such as HIV or hepatitis C virus (HCV), do not have a reflective exonuclease.…”

Section: Sars-cov-2 Life Cyclementioning

confidence: 99%

Oral antivirals for the prevention and treatment of SARS-CoV-2 infection

Soriano¹,

de-Mendoza²,

Edagwa³

et al. 2022

AIDSRev

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Vaccines and antivirals are the classical weapons deployed to contain, prevent, and treat life-threatening viral illnesses. Specifically, for SARS-CoV-2 infection, vaccines protect against severe COVID-19 disease manifestations and complications. However, waning immunity and emergence of vaccine escape mutants remains a growing threat. This is highlighted by the current surge of the omicron COVID-19 variant. Thus, there is a race to find treatment alternatives. We contend that oral small molecule antivirals that halt SARS-CoV-2 infection are essential. Compared to currently available monoclonal antibodies and remdesivir, where parenteral administration is required, oral antivirals offer treatments in an outpatient setting with dissemination available on a larger scale. In response to this need at 2021's end, regulatory agencies provided emergency use authorization for both molnupiravir and nirmatrelvir. These medicines act on the viral polymerase and protease, respectively. Each is given for 5 days and can reduce disease progression by 30% and 89%, respectively. The advent of additional oral antivirals, the assessment of combination therapies, the formulation of extended-release medications, and their benefit for both early treatment and prophylaxis will likely transform the landscape of the COVID-19 pandemic.

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“…IAVs and CoVs harbor single-stranded RNA genomes (negative or positive sense, respectively). High mutation rates occur during replication, which allows them to evolve rapidly [ 22 , 23 ]. There is much evidence that CoVs can limit their mutation rates due to a proofreading mechanism of their polymerase [ 24 , 25 ].…”

Section: Emergence Transmission and Adaptation To Humansmentioning

confidence: 99%

“…There is much evidence that CoVs can limit their mutation rates due to a proofreading mechanism of their polymerase [ 24 , 25 ]. However, it is unclear to what extent this proofreading mechanism is limiting CoVs diversification in an epidemiological context [ 23 , 26 ]. Both viral families also undergo evolutionary shortcuts (reassortment of genomic segments for IAVs and homologous recombination for CoVs), which may favor the emergence of pandemic viruses.…”

Section: Emergence Transmission and Adaptation To Humansmentioning

confidence: 99%

Influenza viruses and coronaviruses: Knowns, unknowns, and common research challenges

et al. 2021

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The development of safe and effective vaccines in a record time after the emergence of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a remarkable achievement, partly based on the experience gained from multiple viral outbreaks in the past decades. However, the Coronavirus Disease 2019 (COVID-19) crisis also revealed weaknesses in the global pandemic response and large gaps that remain in our knowledge of the biology of coronaviruses (CoVs) and influenza viruses, the 2 major respiratory viruses with pandemic potential. Here, we review current knowns and unknowns of influenza viruses and CoVs, and we highlight common research challenges they pose in 3 areas: the mechanisms of viral emergence and adaptation to humans, the physiological and molecular determinants of disease severity, and the development of control strategies. We outline multidisciplinary approaches and technological innovations that need to be harnessed in order to improve preparedeness to the next pandemic.

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Mutation Rates, Mutation Frequencies, and Proofreading-Repair Activities in RNA Virus Genetics

Cited by 99 publications

References 120 publications

Mutation profile of SARS-CoV-2 genome in a sample from the first year of the pandemic in Colombia

Mutation profile of SARS-CoV-2 genome in a sample from the first year of the pandemic in Colombia

Oral antivirals for the prevention and treatment of SARS-CoV-2 infection

Influenza viruses and coronaviruses: Knowns, unknowns, and common research challenges

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