BioAider: An efficient tool for viral genome analysis and its application in tracing SARS-CoV-2 transmission

Zhou, Zhan; Qiu, Ye; Pu, Ying; Huang, Xun; Ge, Xin

doi:10.1016/j.scs.2020.102466

Cited by 85 publications

(69 citation statements)

References 58 publications

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“…Mutation sites comparing to the strain Wuhun-Hu-1 were analyzed by BioAider (V1.314) (17). (A) The total mutation (synonymous and nonsynonymous) in spike gene; (B) The nonsynonymous and synonymous mutations in spike gene; (C) The total mutations and nonsynonymous mutations in RBD.…”

Section: Resultsmentioning

confidence: 99%

“…Selection pressure analyses were conducted using the Nei-Gojobori method(jukes-cantor model) with Mega X(version 10.0.2)(20, 21) . Substitution mutation analyses of mutants are performed compared with Wuhan-Hu-01 sequence using BioAider (version 1.314)(17). Phylogenetic analyses were conducted with Iqtree2, applying the maximum-likelihood method with 1000 bootstrap replicates using GTR+F+R3 model by MFP ModelFinder (35).…”

Section: Methodsmentioning

confidence: 99%

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V367F mutation in SARS-CoV-2 spike RBD emerging during the early transmission phase enhances viral infectivity through increased human ACE2 receptor binding affinity

Zhou

Dai

et al. 2020

Preprint

128

121

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250 words 25 Importance: 150 words 26 Abstract 28 A novel coronavirus SARS-CoV-2 is associated with the current global pandemic of Coronavirus 29Disease 2019 . Spike protein receptor-binding domain (RBD) of SARS-CoV-2 is the 30 critical determinant of viral tropism and infectivity. To investigate whether the mutations in the RBD 31 have altered the receptor binding affinity and caused these strains more infectious, we performed 32 molecular dynamics simulations of the binding affinity between the mutant SARS-CoV-2 RBDs to 33 date and the human ACE2 receptor. Among 1609 genomes of global SARS-CoV-2 strains, 32 34 non-synonymous RBD mutants were identified and clustered into 9 mutant types under high positive 35 selection pressure. Three mutant types (V367F, W436R, and D364Y) emerging in Wuhan, Shenzhen, 36 Hong Kong, and France, displayed higher human ACE2 affinity, and probably higher infectivity. This 37 is due to the enhanced structural stabilization of the RBD beta-sheet scaffold. High frequencies of 38 RBD mutations were identified: V367F from five France and one Hong Kong mutants, 13 V483A and 39 7 G476S mutants from the U.S.A. This suggested they originated as novel sub-lineages. The 40 enhancement of the binding affinity of the mutant type (V367F) was further validated by the 41 receptor-ligand binding ELISA assay. The molecular dynamics simulations also indicated that it 42 would be difficult for bat SARS-like CoV to infect humans. However, the pangolin CoV is potentially 43 infectious to humans. The analysis of critical RBD mutations provides further insights into the 44 evolutionary history of SARS-CoV-2 under high selection pressure. An enhancement of the 45 SARS-CoV-2 binding affinity to human ACE2 receptor reveals higher infectivity of the mutant 46 strains. 47 48 Importance 49 A novel coronavirus SARS-CoV-2 has caused the pandemic of COVID-19. The origin of 50 SARS-CoV-2 was associated with zoonotic infections. The spike protein receptor-binding domain 51 (RBD) is identified as the critical determinant of viral tropism and infectivity. Thus, whether the 52 mutations in the RBD of the circulating SARS-CoV-2 strains have altered the receptor binding 53affinity and caused these strains more infectious, should be paid more attentions to. Here, 32 54 non-synonymous RBD mutants were identified and clustered into 9 mutant types under high positive 55 . CC-BY-NC-ND 4.0 International license (which was not certified by peer review) is the author/funder. It is made available under a selection pressure, suggesting they originated as novel sub-lineages. Three mutant types displayed 56 higher human ACE2 affinity, and probably higher infectivity, one of which (V367F) was validated 57 by wet bench. The RBD mutation analysis provides insights into SARS-CoV-2 evolution. The 58 emergence of RBD mutations with increased human ACE2 affinity reveals higher risk of severe 59 morbidity and mortality during a sustained COVID-19 pandemic, particularly if no effective 60 precautions are implemented. 61 62

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

V367F mutation in SARS-CoV-2 spike RBD emerging during the early transmission phase enhances viral infectivity through increased human ACE2 receptor binding affinity

Zhou

Dai

et al. 2020

Preprint

128

121

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show abstract

“…N protein mutates quicker than other proteins of SARS‐CoV‐2. The reasons might lie within the structural flexibility of this protein especially in its intrinsically disordered regions that account about the half of the total amino acids 12 . This virus was placed in between other two dominant human coronaviruses in light of N protein variations (Table 1).…”

Section: Discussionmentioning

confidence: 99%

Evolutionary dynamics of SARS‐CoV‐2 nucleocapsid protein and its consequences

Rahman

Islam

Alam³

et al. 2020

Journal of Medical Virology

116

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The emerged novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has created a global health crisis that warrants an accurate and detailed characterization of the rapidly evolving viral genome for understanding its epidemiology, pathogenesis, and containment. Here, we explored 61,485 sequences of the nucleocapsid (N) protein, a potent diagnostic and prophylactic target, for identifying the mutations to review their roles in real‐time polymerase chain reaction based diagnosis and observe consequent impacts. Compared to the Wuhan reference strain, a total of 1034 unique nucleotide mutations were identified in the mutant strains (49.15%, n = 30,221) globally. Of these mutations, 367 occupy primer binding sites including the 3′‐end mismatch to the primer‐pair of 11 well‐characterized primer sets. Noteworthily, CDC (USA) recommended the N2 primer set contained a lower mismatch than the other primer sets. Moreover, 684 amino acid (aa) substitutions were located across 317 (75.66% of total aa) unique positions including 82, 21, and 83 of those in the RNA binding N‐terminal domain (NTD), SR‐rich region, and C‐terminal dimerization domain, respectively. Moreover, 11 in‐frame deletions, mostly (n = 10) within the highly flexible linker region, were revealed, and the rest was within the NTD region. Furthermore, we predicted the possible consequence of high‐frequency mutations (≥20) and deletions on the tertiary structure of the N protein. Remarkably, we observed that a high frequency (67.94% of mutated sequences) co‐occuring mutations (R203K and G204R) destabilized and decreased overall structural flexibility. The N protein of SARS‐CoV‐2 comprises an average of 1.2 mutations per strain compared to 4.4 and 0.4 in Middle East respiratory syndrome‐related coronavirus and SARS‐CoV, respectively. Despite being proposed as the alternative target to spike protein for vaccine and therapeutics, the ongoing evolution of the N protein may challenge these endeavors, thus needing further immunoinformatics analyses. Therefore, continuous monitoring is required for tracing the ongoing evolution of the SARS‐CoV‐2 N protein in prophylactic and diagnostic interventions.

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“…COVID-19 is a global challenge, requiring cross-disciplinary cooperation and research to control, in order to maintain the sustainable development of society. Computational biology, big data and artificial intelligence are being used in daily monitoring, prevention and treatment of infectious diseases ( Ahmed, Ahmad, Rodrigues, Jeon, & Din, 2020 ; Bhattacharya et al, 2020 ; Loey, Manogaran, Taha, & Khalifa, 2020 ; Zhou, Qiu, Pu, Huang, & Ge, 2020 ). Abboah-Offei et al (2021) investigated the impact face mask has had in controlling transmission of respiratory viral infections.…”

Section: Discussionmentioning

confidence: 99%

Assessing and controlling infection risk with Wells-Riley model and spatial flow impact factor (SFIF)

Guo

Qian

Sun

et al. 2021

Sustainable Cities and Society

102

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BioAider: An efficient tool for viral genome analysis and its application in tracing SARS-CoV-2 transmission

Cited by 85 publications

References 58 publications

V367F mutation in SARS-CoV-2 spike RBD emerging during the early transmission phase enhances viral infectivity through increased human ACE2 receptor binding affinity

V367F mutation in SARS-CoV-2 spike RBD emerging during the early transmission phase enhances viral infectivity through increased human ACE2 receptor binding affinity

Evolutionary dynamics of SARS‐CoV‐2 nucleocapsid protein and its consequences

Assessing and controlling infection risk with Wells-Riley model and spatial flow impact factor (SFIF)

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