Hotspots for mutations in the SARS-CoV-2 spike glycoprotein: a correspondence analysis

Rahbar, Mahtab; Jahangiri, Abolfazl; Khalili, Saeed; Zarei, Mahboubeh; Mehrabani-Zeinabad, Kamran; Khalesi, Bahman; Pourzardosht, Navid; Hessami, Anahita; Nezafat, Navid; Sadraei, Saman; Negahdaripour, Manica

doi:10.1038/s41598-021-01655-y

Cited by 9 publications

(10 citation statements)

References 105 publications

(141 reference statements)

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“…The pentameric E protein from the SARS-CoV-2 has been modelled taking its solid-state NMR structure as the template (PDB id: 7K3G) (26), whose viroporin activity through the single channel formed by its TM region (8-40) has been analysed in a previous study (13) (Figure 4A). The protein-membrane complex was equilibrated energetically followed by 5 ns of MD simulation to analyse the continuous water channel formation through the proposed pore (Supplementary Movie 2).…”

Section: Resultsmentioning

confidence: 99%

“…A. Insertion and equilibration of E protein (8-40) of SARS-CoV-2 in a membrane system mimicking the ERGIC of human cells. The membrane is not shown in the figure to ease the visualisation of the molecular machine.…”

Section: Resultsmentioning

confidence: 99%

“…SARS-CoV-2 has acquired several mutation hotspots in the Spike (S) protein across all its variants (40,41) which contributes to the increased pathogenicity of the variants (17). However, there are several other important viral proteins which play decisive roles in the viral life cycle and have remained conserved across the variants.…”

Section: Discussionmentioning

confidence: 99%

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SARS- CoV-2 viroporins: A multi-omics insight from nucleotides to amino acids

Sarkar¹,

Etheimer

Saha³

2021

Preprint

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COVID-19 is caused by SARS-CoV-2 which has affected nearly 220 million people worldwide and death toll close to 5 million as of present day. The approved vaccines are lifesaving yet temporary solutions to such a devastating pandemic. Viroporins are important players of the viral life cycle of SARS-Cov-2 and one of the primary determinants of its pathogenesis. We studied the two prominent viroporins of SARS-CoV-2 (i) Orf3a and (ii) Envelope (E) protein from a structural point of view. Orf3a has several hotspots of mutations which has been reported in SARS-CoV-2 with respect to SARS-CoV-1. Mutations in SARS-CoV-2 Orf3a channel forming residues enhances the formation of a prominent the inter-subunit channel, which was not present in the SARS-CoV-1 Orf3a. This enhanced structural feature can be correlated with higher channelling activity in SARS-CoV-2 than in SARS-CoV-1. On the other hand, E protein is one of the most conserved protein among the SARS-CoV proteome. We found that the water molecules form networks of electrostatic interactions with the polar residues in the E protein putative wetted condition while no water channel formation was observed in the putative dewetted condition. This aqueous medium mediates the non-selective translocation of cations thus affecting the ionic homeostasis of the host cellular compartments. This ionic imbalance leads to increased inflammatory response in the host cell. Our results shed light into the mechanism of viroporin action, which can be leveraged for the development of antiviral therapeutics. Furthermore, our results corroborate with previously published transcriptomic data from COVID-19 infected lung alveolar cells where inflammatory responses and molecular regulators directly impacted by ion channelling were upregulated. These observations overlap with transcript upregulation observed in diseases having acute lung injury, pulmonary fibrosis and Acute Respiratory Distress Syndrome (ARDS).

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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SARS- CoV-2 viroporins: A multi-omics insight from nucleotides to amino acids

Sarkar¹,

Etheimer

Saha³

2021

Preprint

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“…Focusing on the correlations between the RBD and residues distant to it in the S protein, Ray et al built a protein graph connectivity network and calculated the betweenness centrality. A modification of the average shortest path length was used in ref . Saha et al employed various network measures to identify the spreader nodes in the SARS-CoV-human protein–protein interaction network, hoping to find possible lineage with the disease propagation pattern of the COVID-19 pandemic.…”

Section: Methods and Approachesmentioning

confidence: 99%

Methodology-Centered Review of Molecular Modeling, Simulation, and Prediction of SARS-CoV-2

Gao¹,

Wang²,

Chen³

et al. 2022

Chem. Rev.

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Despite tremendous efforts in the past two years, our understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), virus–host interactions, immune response, virulence, transmission, and evolution is still very limited. This limitation calls for further in-depth investigation. Computational studies have become an indispensable component in combating coronavirus disease 2019 (COVID-19) due to their low cost, their efficiency, and the fact that they are free from safety and ethical constraints. Additionally, the mechanism that governs the global evolution and transmission of SARS-CoV-2 cannot be revealed from individual experiments and was discovered by integrating genotyping of massive viral sequences, biophysical modeling of protein–protein interactions, deep mutational data, deep learning, and advanced mathematics. There exists a tsunami of literature on the molecular modeling, simulations, and predictions of SARS-CoV-2 and related developments of drugs, vaccines, antibodies, and diagnostics. To provide readers with a quick update about this literature, we present a comprehensive and systematic methodology-centered review. Aspects such as molecular biophysics, bioinformatics, cheminformatics, machine learning, and mathematics are discussed. This review will be beneficial to researchers who are looking for ways to contribute to SARS-CoV-2 studies and those who are interested in the status of the field.

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“…Bio- and immuno-informatics approaches have provided robust and reliable tools for various molecular biology studies 37 , 77 – 89 from which novel vaccine design strategies are also highly benefited 66 , 90 .…”

Section: Introductionmentioning

confidence: 99%

A unique antigen against SARS-CoV-2, Acinetobacter baumannii, and Pseudomonas aeruginosa

Rahbar

Mubarak

Hessami

et al. 2022

Sci Rep

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The recent outbreak of COVID-19 has increased hospital admissions, which could elevate the risk of nosocomial infections, such as A. baumannii and P. aeruginosa infections. Although effective vaccines have been developed against SARS-CoV-2, no approved treatment option is still available against antimicrobial-resistant strains of A. baumannii and P. aeruginosa. In the current study, an all-in-one antigen was designed based on an innovative, state-of-the-art strategy. In this regard, experimentally validated linear epitopes of spike protein (SARS-CoV-2), OmpA (A. baumannii), and OprF (P. aeruginosa) were selected to be harbored by mature OmpA as a scaffold. The selected epitopes were used to replace the loops and turns of the barrel domain in OmpA; OprF311–341 replaced the most similar sequence within the OmpA, and three validated epitopes of OmpA were retained intact. The obtained antigen encompasses five antigenic peptides of spike protein, which are involved in SARS-CoV-2 pathogenicity. One of these epitopes, viz. QTQTNSPRRARSV could trigger antibodies preventing super-antigenic characteristics of spike and alleviating probable autoimmune responses. The designed antigen could raise antibodies neutralizing emerging variants of SARS-CoV-2 since at least two epitopes are consensus. In conclusion, the designed antigen is expected to raise protective antibodies against SARS-CoV-2, A. baumannii, and P. aeruginosa.

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Hotspots for mutations in the SARS-CoV-2 spike glycoprotein: a correspondence analysis

Cited by 9 publications

References 105 publications

SARS- CoV-2 viroporins: A multi-omics insight from nucleotides to amino acids

SARS- CoV-2 viroporins: A multi-omics insight from nucleotides to amino acids

Methodology-Centered Review of Molecular Modeling, Simulation, and Prediction of SARS-CoV-2

A unique antigen against SARS-CoV-2, Acinetobacter baumannii, and Pseudomonas aeruginosa

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