Insights on early mutational events in SARS-CoV-2 virus reveal founder effects across geographical regions

Farkas, Carlos; Fuentes-Villalobos, Francisco; Garrido, José; Haigh, Jody J.; Barría, María Inés

doi:10.7717/peerj.9255

Cited by 30 publications

(32 citation statements)

References 33 publications

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“…The founder effect, as a reason for genetic diversification, has been reported in many viruses and pathogens [55][56][57][58] including SARS-CoV [44], and, in HIV, has been an immense source of polymorphisms and evolution [55]. In a study evaluating the distribution of mutations in SARS-CoV-2 genomes, the clonal nature of mutations in different geographical regions was detected, leading to the assignment of the founder effect as the cause [59]. In the initial phases of endemic viral infections, viruses are under a constant selection pressure and certain lineages can eventually face extinction because of the competition with their more reproductively capable counterparts.…”

Section: Genomic Stability Estimation Of Sars-cov-2 Orf8mentioning

confidence: 99%

SARS-CoV-2 ORF8 and SARS-CoV ORF8ab: Genomic Divergence and Functional Convergence

et al. 2020

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The COVID-19 pandemic, in the first seven months, has led to more than 15 million confirmed infected cases and 600,000 deaths. SARS-CoV-2, the causative agent for COVID-19, has proved to be a great challenge for its ability to spread in asymptomatic stages and the diverse disease spectrum it has generated. This has created a challenge of unimaginable magnitude, not only affecting human health and life but also potentially generating a long-lasting socioeconomic impact. Both medical sciences and biomedical research have also been challenged, consequently leading to a large number of clinical trials and vaccine initiatives. While known proteins of pathobiological importance are targets for these therapeutic approaches, it is imperative to explore other factors of viral significance. Accessory proteins are one such trait that have diverse roles in coronavirus pathobiology. Here, we analyze certain genomic characteristics of SARS-CoV-2 accessory protein ORF8 and predict its protein features. We have further reviewed current available literature regarding its function and comparatively evaluated these and other features of ORF8 and ORF8ab, its homolog from SARS-CoV. Because coronaviruses have been infecting humans repeatedly and might continue to do so, we therefore expect this study to aid in the development of holistic understanding of these proteins. Despite low nucleotide and protein identity and differentiating genome level characteristics, there appears to be significant structural integrity and functional proximity between these proteins pointing towards their high significance. There is further need for comprehensive genomics and structural-functional studies to lead towards definitive conclusions regarding their criticality and that can eventually define their relevance to therapeutics development.

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Section: Genomic Stability Estimation Of Sars-cov-2 Orf8mentioning

confidence: 99%

SARS-CoV-2 ORF8 and SARS-CoV ORF8ab: Genomic Divergence and Functional Convergence

et al. 2020

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“…While the founder effect - whereby a small number of strains establish a new population - is a possible explanation for the increasing prevalence of the G614 variant 6 , accumulating evidence points to an evolutionary fitness advantage conferred on SARS-CoV-2 by this mutation. First, sequence analysis has revealed that the D614 variant was well established within several populations before the arrival of the G614 variant 1 .…”

Section: Introductionmentioning

confidence: 99%

The SARS-CoV-2 Spike mutation D614G increases entry fitness across a range of ACE2 levels, directly outcompetes the wild type, and is preferentially incorporated into trimers

Michaud

Boland

Rabi

2020

Preprint

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Early in the current pandemic, the D614G mutation arose in the Spike protein of SARS-CoV-2 and quickly became the dominant variant globally. Mounting evidence suggests D614G enhances viral entry. Here we use a direct competition assay with single-cycle viruses to show that D614G outcompetes the wildtype. We developed a cell line with inducible ACE2 expression to confirm that D614G more efficiently enters cells with ACE2 levels spanning the different primary cells targeted by SARS-CoV-2. Using a new assay for crosslinking and directly extracting Spike trimers from the pseudovirus surface, we found an increase in trimerization efficiency and viral incorporation of D614G protomers. Our findings suggest that D614G increases infection of cells expressing a wide range of ACE2, and informs the mechanism underlying enhanced entry. The tools developed here can be broadly applied to study other Spike variants and SARS-CoV-2 entry, to inform functional studies of viral evolution and vaccine development.

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“…Although a vaccine for COVID-19 would be an optimal solution, the prospects for a safe and effective vaccine are murky at best and probably not a viable option in the next two years due to mutational variation of the virus and potential vaccine enhancement of viral infection. 8,9 Herd immunity to SARS-CoV-2 also may be difficult to achieve because the infection rate is too low. 10,11 Therefore, an alternate prevention strategy is needed when social distancing is phased out during economic recovery.…”

Section: Introductionmentioning

confidence: 99%

<p>Flattening the Risk: Pre-Exposure Prophylaxis for COVID-19</p>

Stricker¹,

Fesler²

2020

IDR

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To date, more than 35 million people worldwide have been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the agent of coronavirus disease 2019 (COVID-19), and more than one million have died in the COVID-19 pandemic. International economies are stalled and social isolation based on palpable fear of death remains the order of the day. The United States and other countries are moving toward resuming work activities and social interaction to boost economic recovery. While this makes financial sense, from a medical perspective our population has already suffered and will continue to suffer severe losses in the absence of a viable aggressive prophylaxis strategy for SARS-CoV-2. Herein, we present a plan to address this problem.

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Insights on early mutational events in SARS-CoV-2 virus reveal founder effects across geographical regions

Cited by 30 publications

References 33 publications

SARS-CoV-2 ORF8 and SARS-CoV ORF8ab: Genomic Divergence and Functional Convergence

SARS-CoV-2 ORF8 and SARS-CoV ORF8ab: Genomic Divergence and Functional Convergence

The SARS-CoV-2 Spike mutation D614G increases entry fitness across a range of ACE2 levels, directly outcompetes the wild type, and is preferentially incorporated into trimers

<p>Flattening the Risk: Pre-Exposure Prophylaxis for COVID-19</p>

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