Molecular dynamics simulation study reveals effects of key mutations on spike protein structure in SARS-CoV-2

Lon, Jerome Rumdon; Xi, Binbin; Zhong, Bingxu; Zheng, Yu; Chen, Zixi; Qiu, Ruoran; Zhang, Siqing; Guo, Pei; Du, Hongli

doi:10.1101/2021.02.03.429495

Cited by 3 publications

(4 citation statements)

References 61 publications

(91 reference statements)

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“…From the 50 ns molecular dynamics simulation carried out in GROMACS, the complex between the ACE2 receptor and the Spike protein variant of B.1.617 was found to be most stable considering its structural deviation, local area flexibility, state of folding, and susceptibility to disruption by solvents ( Fig 10 ). These findings coincide with those reported in other studies and the enhanced Spike protein stability of the B.1.617 is likely to contribute to the efficiency of transmission of SARS-CoV-2 [ 88 – 90 ].…”

Section: Discussionsupporting

confidence: 92%

Wave-wise comparative genomic study for revealing the complete scenario and dynamic nature of COVID-19 pandemic in Bangladesh

et al. 2021

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As the COVID-19 pandemic continues to ravage across the globe and take millions of lives and like many parts of the world, the second wave of the pandemic hit Bangladesh, this study aimed at understanding its causative agent, SARS-CoV-2 at the genomic and proteomic level and provide precious insights about the pathogenesis, evolution, strengths and weaknesses of the virus. As of Mid-June 2021, over 1500 SARS-CoV-2 genomesequences have been deposited in the GISAID database from Bangladesh which were extracted and categorized into two waves. By analyzing these genome sequences, it was discovered that the wave-2 samples had a significantly greater average rate of mutation/sample (30.79%) than the wave-1 samples (12.32%). Wave-2 samples also had a higher frequency of deletion, and transversion events. During the first wave, the GR clade was the most predominant but it was replaced by the GH clade in the latter wave. The B.1.1.25 variant showed the highest frequency in wave-1 while in case of wave-2, the B.1.351.3 variant, was the most common one. A notable presence of the delta variant, which is currently at the center of concern, was also observed. Comparison of the Spike protein found in the reference and the 3 most common lineages found in Bangladesh namely, B.1.1.7, B.1.351, B.1.617 in terms of their ability to form stable complexes with ACE2 receptor revealed that B.1.617 had the potential to be more transmissible than others. Importantly, no indigenous variants have been detected so far which implies that the successful prevention of import of foreign variants can diminish the outbreak in the country.

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Section: Discussionsupporting

confidence: 92%

Wave-wise comparative genomic study for revealing the complete scenario and dynamic nature of COVID-19 pandemic in Bangladesh

et al. 2021

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“…49,50 Lon et al observed mutant models (D614G, A222V, N501Y, T716I, S982A, D1118H) of SARS-CoV-2 spike protein are more stable and more compact, as the mutant models displayed less RMSD and Rg values in molecular dynamic simulation study. 49 Another study reported that W80R mutation in kinase B protein targeting ovarian cancer is more stable as it has less RMSD than wild-type model. 50 Khan et al reported that mutant models exhibit more intramolecular hydrogen bonds than wild-type of Rab5a protein.…”

Section: Discussionmentioning

confidence: 99%

“…Studies have performed molecular dynamic simulation analysis to observe effect of point mutations on protein 49,50 . Lon et al.…”

Section: Discussionmentioning

confidence: 99%

Analysis of highly frequent point mutations in glycoprotein C, glycoprotein N, and nucleoprotein of CCHFV

Kaushal,

Baranwal

2023

Biotech and App Biochem

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Crimean‐Congo hemorrhagic fever virus (CCHFV) is classified among top 10 priority pathogens by World Health Organization. CCHFV belongs to Bunyaviridae family and negative sense ssRNA genome composed of three RNA segments: L, M, and S. RNA viruses show higher mutation rate as compared to DNA viruses. To gain deeper understanding of impact of point mutations in CCHFV M and S segment, mutation profiling, homology modeling, and molecular dynamic (MD) simulation were performed. Structural glycoproteins (glycoprotein C [Gc] and glycoprotein N [Gn]) of CCHFV are important for host–virus interaction and genome packaging, whereas CCHFV nucleoprotein (NP) is crucial for viral replication. Hence, current study is focused on evaluation of eight mutations in structural glycoproteins (Gc: 7 and Gn: 1) of M segment and seven mutations in NP of S segment. All these mutations were highly frequent, with mutation frequency between 0.81 and 1.0 and found to be persistent in the recent strains of CCHFV. Solubility analysis predicted that selected point mutations reduce solubility of Gc protein and increase solubility of Gn and NP proteins. MD simulation study deciphered that A1046V and G1158E in Gc protein, I778T in Gn protein, and H195R in NP protein displayed large deviation and fluctuation, and affected intramolecular interactions. In conclusion, we observed that point mutations could impact structure, stability, and host–virus interaction of protein, and might lead to evolution of new strains for better survival and drug resistance.

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“…It was found in 53.8% of all uploaded sequences in November 2020 and assumed to influence viral transmissivity and antigenicity (Hodcroft et al, 2020; Bartolini et al, 2020). The mutation might, however, enhance the ability of the protein to interact with the environment (Lon et al, 2021). The M gene is also featured by a frequent mutation - C26801G (L93L) is found in 21.82%, which constitutes between 53.4% and 43.2% of all uploads from November 2020 to December 2020.…”

Section: Discussionmentioning

confidence: 99%

Analysis of 329,942 SARS-CoV-2 records retrieved from GISAID database

Zelenova

Ivanova²,

Semyonov³

et al. 2021

Preprint

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Background: The 31st of December 2019 was when the World Health Organization received a report about an outbreak of pneumonia of unknown etiology in the Chinese city of Wuhan. The outbreak was the result of the novel virus labeled as SARS-CoV-2, which spread to about 220 countries and caused approximately 3,311,780 deaths, infecting more than 159,319,384 people by May 12th, of 2021. The virus caused a worldwide pandemic leading to panic, quarantines, and lockdowns - although none of its predecessors from the coronavirus family have ever achieved such a scale. The key to understanding the global success of SARS-CoV-2 is hidden in its genome. Materials and Methods: We retrieved data for 329,942 SARS-CoV-2 records uploaded to the GISAID database from the beginning of the pandemic until the 8th of January 2021. To process the data, a Python variant detection script was developed, using pairwise2 from the BioPython library. Pandas, Matplotlib, and Seaborn, were applied to visualize the data. Genomic coordinates were obtained from the UCSC Genome Browser (https://genome.ucsc.edu/). Sequence alignments were performed for every gene separately. Genomes less than 26,000 nucleotides long were excluded from the research. Clustering was performed using HDBScan. Results: Here, we addressed the genetic variability of SARS-CoV-2 using 329,942 worldwide samples. The analysis yielded 155 genome variations (SNPs and deletions) in more than 0.3% of the sequences. Nine common SNPs were present in more than 20% of the samples. Clustering results suggested that a proportion of people (2.46%) were infected with a distinct subtype of the B.1.1.7 variant. The subtype may be characterized by four to six additional mutations, with four being a more frequent option (G28881A, G28882A, and G28883C in the N gene, A23403G in S, A28095T in ORF8, G25437T in ORF3a). Two clusters were formed by mutations in the samples uploaded predominantly by Denmark and Australia, which may indicate the emergence of "Danish" and "Australian" variants. Five clusters were linked to increased/decreased age, shifted gender ratio, or both. According to a correlation coefficient matrix, 69 mutations correlate with at least one other mutation (correlation coefficient greater than 0.7). We also addressed the completeness of the GISAID database, where between 77% and 93% of the fields were either left blank or filled incorrectly. Metadata mining analysis has led to a hypothesis about gender inequality in medical care in certain countries. Finally, we found ORF6 and E as the most conserved genes (96.15% and 94.66% of the sequences totally match the reference, respectively), making them potential targets for vaccines and treatment. Our results indicate areas of the SARS-CoV-2 genome that researchers can focus on for further structural and functional analysis.

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Molecular dynamics simulation study reveals effects of key mutations on spike protein structure in SARS-CoV-2

Cited by 3 publications

References 61 publications

Wave-wise comparative genomic study for revealing the complete scenario and dynamic nature of COVID-19 pandemic in Bangladesh

Wave-wise comparative genomic study for revealing the complete scenario and dynamic nature of COVID-19 pandemic in Bangladesh

Analysis of highly frequent point mutations in glycoprotein C, glycoprotein N, and nucleoprotein of CCHFV

Analysis of 329,942 SARS-CoV-2 records retrieved from GISAID database

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