Sequence Similarity Network Analysis Provides Insight into the Temporal and Geographical Distribution of Mutations in SARS-CoV-2 Spike Protein.

Severe acute respiratory syndrome-related coronavirus (SARS-CoV-2), which still infects hundreds of thousands of people globally each day despite various countermeasures, has been mutating rapidly. Mutations in the spike (S) protein seem to play a vital role in viral stability, transmission, and adaptability. Therefore, to control the spread of the virus, it is important to gain insight into the evolution and transmission of the S protein. This study deals with the temporal and geographical distribution of mutant S proteins from sequences gathered across the US over a period of 19 months in 2020 and 2021. The S protein sequences are studied using two approaches: (i) multiple sequence alignment is used to identify prominent mutations and highly mutable regions and (ii) sequence similarity networks are subsequently employed to gain further insight and study mutation profiles of concerning variants across the defined time periods and states. Additionally, we tracked the variants using visualizations on geographical maps. The visualizations produced using the Directed Weighted All Nearest Neighbors (DiWANN) networks and maps provided insights into the transmission of the virus that reflect well the statistics reported for the time periods studied. We found that the networks created using DiWANN are superior to commonly used approximate distance networks created using BLAST bitscores. The study offers a richer computational approach to analyze the transmission profile of the prominent S protein mutations in SARS-CoV-2 and can be extended to other proteins and viruses.

Sequence determinants of human-cell entry identified in ACE2-independent bat sarbecoviruses: A combined laboratory and computational network science approach.

BACKGROUND: The sarbecovirus subgenus of betacoronaviruses is widely distributed throughout bats and other mammals globally and includes human pathogens, SARS-CoV and SARS-CoV-2. The most studied sarbecoviruses use the host protein, ACE2, to infect cells. Curiously, the majority of sarbecoviruses identified to date do not use ACE2 and cannot readily acquire ACE2 binding through point mutations. We previously screened a broad panel of sarbecovirus spikes for cell entry and observed bat-derived viruses that could infect human cells, independent of ACE2. Here we further investigate the sequence determinants of cell entry for ACE2-independent bat sarbecoviruses. METHODS: We employed a network science-based approach to visualize sequence and entry phenotype similarities across the diversity of sarbecovirus spike protein sequences. We then verified these computational results and mapped determinants of viral entry into human cells using recombinant chimeric spike proteins within an established viral pseudotype assay. FINDINGS: We show ACE2-independent viruses that can infect human and bat cells in culture have a similar putative receptor binding motif, which can impart human cell entry into other bat sarbecovirus spikes that cannot otherwise infect human cells. These sequence determinants of human cell entry map to a surface-exposed protrusion from the predicted bat sarbecovirus spike receptor binding domain structure. INTERPRETATION: Our findings provide further evidence of a group of bat-derived sarbecoviruses with zoonotic potential and demonstrate the utility in applying network science to phenotypic mapping and prediction. FUNDING: This work was supported by Washington State University and the Paul G. Allen School for Global Health.

Sequence similarity analysis between SARS-COV-2 and other viruses based on variant logic framework and topological entropy

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) popular in just a few months the world, the present study found that the virus belongs to the β-coronavirus family. We study the sequence similarity, which can be coronavirus vaccine development and analysis provides a scientific help, including SARS-CoV-2 high similarity with Bat-CoV, SARS, etc. But the low accuracy of long time-consuming problems sequences analysis method. In this paper, the topological entropy of different combination dimensions of each sequence was calculated based on the Variant Logic Framework. the sequences of SARS CoV-2 and other categories of viruses were taken as input data. The sequence similarity matrix of mutual information among different sequences was obtained by calculating Euclidean distance. Finally, using a visualization diagram, generate the phylogenetic tree. The experimental results show that topology entropy is fast and effective for virus sequence processing and similarity analysis, which also provides a new idea for virus sequence research and traceability. © 2021 ACM.

COVID-19 and iron dysregulation: distant sequence similarity between hepcidin and the novel coronavirus spike glycoprotein.

The spike glycoprotein of the SARS-CoV-2 virus, which causes COVID-19, has attracted attention for its vaccine potential and binding capacity to host cell surface receptors. Much of this research focus has centered on the ectodomain of the spike protein. The ectodomain is anchored to a transmembrane region, followed by a cytoplasmic tail. Here we report a distant sequence similarity between the cysteine-rich cytoplasmic tail of the coronavirus spike protein and the hepcidin protein that is found in humans and other vertebrates. Hepcidin is thought to be the key regulator of iron metabolism in humans through its inhibition of the iron-exporting protein ferroportin. An implication of this preliminary observation is to suggest a potential route of investigation in the coronavirus research field making use of an already-established literature on the interplay of local and systemic iron regulation, cytokine-mediated inflammatory processes, respiratory infections and the hepcidin protein. The question of possible homology and an evolutionary connection between the viral spike protein and hepcidin is not assessed in this report, but some scenarios for its study are discussed.