Genetic spectrum and distinct evolution patterns of SARS-CoV-2

Liu, Sheng; Shen, Jikui; Fang, Shuyi; Li, Kailing; Liu, Juli; Yang, Lei; Hu, Chang‐Deng; Wan, Jun

doi:10.1101/2020.06.16.20132902

Cited by 37 publications

(62 citation statements)

References 59 publications

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“…Computing the correlation coefficient between the Ab affinity map and the sequence entropy, we found a moderate increase over time ( Figure 4H) from a value of -0.11 in Feb 2020 to 0.38 for sequences sampled at 08-09/2020. While the correlation value of 0.38 is still very low, this may point that escape from Abs mutations are starting to be a more significant part of its population, in accordance with other reports (Li et al, 2020;Weisblum et al, 2020). An increase over months and years in correlation value between the affinity map computed by our model and the evolving mutational landscape of SARS-CoV-2 could indicate that its mutability patterns are being shaped by Ab pressure.…”

Section: Time Evolution Of Sars-cov-2 Mutability Mapsupporting

confidence: 89%

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Viral surface geometry shapes influenza and coronavirus spike evolution through antibody pressure

Amitai

2020

Preprint

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The evolution of circulating viruses is shaped by their need to evade the adaptive immune system. The spike protein which mediates entry to the host cell is the main target of antibody response. Because of the dense presentation of spikes on the viral surface, not all antigenic sites are targeted equally by antibodies, leading to complex immunodominance patterns. We used 3D coarse-grained computational models to estimate the antibody pressure on the seasonal flu H1N1 and the SARS subgenus spikes. Analyzing publically available sequences, we show that antibody pressure, through the geometrical organization of these spikes on the viral surface, shaped their mutability. Studying the mutability patterns of SARS-CoV-2 and the 2009 H1N1 pandemic spikes, we find that they are not predominantly shaped by antibody pressure. However, for SARS-CoV-2, we find that over time, it acquired, at low frequency, several mutations at antibody-accessible positions, which could indicate possible escape as define by our model. Hence, we offer a geometry-based approach to estimate and assess whether a pandemic virus is changing its mutational pattern to that indicative of a circulating virus.

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Section: Time Evolution Of Sars-cov-2 Mutability Mapsupporting

confidence: 89%

“…Since SARS-CoV-2 virus introduction into humans is recent, it probably has not yet evolved extensively to acquire escape mutations from the commutative Ab pressure of the human population (Li et al, 2020). One mutation at the spike (D614G) is now widespread and is thought to support a high viral growth rate (Korber et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Viral surface geometry shapes influenza and coronavirus spike evolution through antibody pressure

Amitai

2020

Preprint

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“…But there were some mutations, such as T85I in nsp2 and P323L in nsp12, found no significant impact on integral protein structure according to our results. However, their high frequency prompt us to further investigate whether they could affect virus characteristics via altering RNA second structure [20], protein stability [21] or partial structure [22]. For instance, experimental research reported that D614G in S could lead to virus infectivity increased by eliminating side-chain hydrogen bond which was only a tiny change in overall protein structure [23], and our data also showed small structural difference between D614G mutant and control (RMSD = 2.33 Å).…”

Section: Discussionmentioning

confidence: 62%

Effects of SARS-CoV-2 Mutations on Protein Structures and Intraviral Protein-Protein Interactions

Tian

Liu

et al. 2020

Preprint

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Since 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) has infected ten millions of people across the globe, and massive mutations in virus genome have occurred during the rapid spread of this novel coronavirus. Variance in protein sequence might lead to change in protein structure and interaction, then further affect the viral physiological characteristics, which could bring tremendous influence on the pandemic. In this study, we investigated 18 non-synonymous mutations in SARS-CoV-2 genome which incidence rates were all ≥1% as of July 15th, 2020, then modeled the mutated protein structures and compared them with the reference ones. The results showed that four types of mutations could cause dramatic changes in protein structures (RMSD ≥5.0 Å), which were Q57H and G251V in open reading frames 3a (ORF3a), S194L and R203K/G204R in nucleocapsid (N). Next, we found that these mutations could affect the binding affinity of intraviral protein interactions. In addition, the hot spots within these docking complexes were altered, among which the mutation Q57H was involved in both Orf3a-Orf8 and Orf3a-S protein interactions. Besides, these mutations were widely distributed all over the world, and their occurrences fluctuated as time went on. Notably, the incidences of R203K/G204R in N and Q57H in Orf3a were both over 50% in some countries. Overall, our findings suggest that SARS-CoV-2 mutations can change viral protein structure, binding affinity and hot spots of the interface, thereby may have impacts on SARS-CoV-2 transmission, diagnosis and treatment of COVID-19.

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“…Example 1: In a strain from Iceland, the succession of mutations G1440A (Gly392Asp, protein Nsp2) and G2891A (Ala876Thr, ubiquitin-like domain of protein Nsp3) is now present in multiple world locations [22]. This sequence ends up with C27661U (which modifies amino acid Gln90 into a premature translation end, near the carboxy-terminal end of protein Orf7a).…”

Section: Mutations Leading To An Early Translation Terminationmentioning

confidence: 99%

Biochemical and mathematical lessons from the evolution of the SARS-CoV-2 virus: paths for novel antiviral warfare

Cluzel¹,

Lambert

Maday³

et al. 2020

Preprint

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In the fight against the spread of COVID-19 the emphasis is on vaccination or on reactivating existing drugs used for other purposes. The tight links that necessarily exist between the virus as it multiplies and the metabolism of its host are systematically ignored. Here we show that the metabolism of all cells is coordinated by the availability of a core building block of the cell’s genome, cytidine triphosphate (CTP). This metabolite is also the key to the synthesis of the viral envelope and to the translation of its genome into proteins. This unique role explains why evolution has led to the early emergence in animals of an antiviral immunity enzyme, viperin, that synthesizes a toxic analogue of CTP. The constraints arising from this dependency guide the evolution of the virus. With this in mind, we explored the real-time experiment taking place before our eyes using probabilistic modelling approaches to the molecular evolution of the virus. We have thus followed, almost on a daily basis, the evolution of the composition of the viral genome to link it to the progeny produced over time, particularly in the form of blooms that sparked a firework of viral mutations. Some of those certainly increase the propagation of the virus. This led us to make out the critical role in this evolution of several proteins of the virus, such as its nucleocapsid N, and more generally to begin to understand how the virus ties up the host metabolism to its own benefit. A way for the virus to escape CTP-dependent control in cells would be to infect cells that are not expected to grow, such as neurons. This may account for unexpected body sites of viral development in the present epidemic.

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Genetic spectrum and distinct evolution patterns of SARS-CoV-2

Cited by 37 publications

References 59 publications

Viral surface geometry shapes influenza and coronavirus spike evolution through antibody pressure

Viral surface geometry shapes influenza and coronavirus spike evolution through antibody pressure

Effects of SARS-CoV-2 Mutations on Protein Structures and Intraviral Protein-Protein Interactions

Biochemical and mathematical lessons from the evolution of the SARS-CoV-2 virus: paths for novel antiviral warfare

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