Structures of SARS-CoV-2 RNA-Binding Proteins and Therapeutic Targets

Khan, Muhammad Tahir; Irfan, Muhammad; Ahsan, Hina; Ahmed, Abrar; Kaushik, Aman Chandra; Khan, Abdul Karim; Chinnasamy, Sathishkumar; Ali, Arif; Wei, Dong‐Qing

doi:10.1159/000513686

Cited by 48 publications

(46 citation statements)

References 100 publications

(112 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…NSP proteins form replication-transcription complexes and mainly participate in biological processes, such as viral replication, protein processing, transcription, and proteolysis. Some function as RNA-dependent RNA polymerases, in addition to binding ATP and zinc ions [ 19 , 20 ]. The E and M proteins may be involved in RNA packaging and virus assembly and release; the E protein has evolved to include a robust membrane topology, and it forms either a cation channel regulated by pH or an ion channel potentially inhibited by gliclazide and memantine [ 19 , 21 – 23 ].…”

Section: Introductionmentioning

confidence: 99%

Neutralizing antibodies for the prevention and treatment of COVID-19

2021

View full text Add to dashboard Cite

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) initiates the infection process by binding to the viral cellular receptor angiotensin-converting enzyme 2 through the receptor-binding domain (RBD) in the S1 subunit of the viral spike (S) protein. This event is followed by virus–cell membrane fusion mediated by the S2 subunit, which allows virus entry into the host cell. Therefore, the SARS-CoV-2 S protein is a key therapeutic target, and prevention and treatment of coronavirus disease 2019 (COVID-19) have focused on the development of neutralizing monoclonal antibodies (nAbs) that target this protein. In this review, we summarize the nAbs targeting SARS-CoV-2 proteins that have been developed to date, with a focus on the N-terminal domain and RBD of the S protein. We also describe the roles that binding affinity, neutralizing activity, and protection provided by these nAbs play in the prevention and treatment of COVID-19 and discuss the potential to improve nAb efficiency against multiple SARS-CoV-2 variants. This review provides important information for the development of effective nAbs with broad-spectrum activity against current and future SARS-CoV-2 strains.

show abstract

Section: Introductionmentioning

confidence: 99%

Neutralizing antibodies for the prevention and treatment of COVID-19

2021

View full text Add to dashboard Cite

show abstract

“…As discussed above, the N proteins are key for incorporating viral RNA into viral progeny particles [ 38 , 39 ]. There, the N-terminal RNA-binding domain binds the RNA and the C-terminal domain via interaction with the M protein functions to anchor the ribonucleoprotein to the viral membrane [ 40 ].…”

Section: Resultsmentioning

confidence: 99%

Intracellular Life Cycle Kinetics of SARS-CoV-2 Predicted Using Mathematical Modelling

Grebennikov

Kholodareva

Sazonov

et al. 2021

Viruses

View full text Add to dashboard Cite

SARS-CoV-2 infection represents a global threat to human health. Various approaches were employed to reveal the pathogenetic mechanisms of COVID-19. Mathematical and computational modelling is a powerful tool to describe and analyze the infection dynamics in relation to a plethora of processes contributing to the observed disease phenotypes. In our study here, we formulate and calibrate a deterministic model of the SARS-CoV-2 life cycle. It provides a kinetic description of the major replication stages of SARS-CoV-2. Sensitivity analysis of the net viral progeny with respect to model parameters enables the identification of the life cycle stages that have the strongest impact on viral replication. These three most influential parameters are (i) degradation rate of positive sense vRNAs in cytoplasm (negative effect), (ii) threshold number of non-structural proteins enhancing vRNA transcription (negative effect), and (iii) translation rate of non-structural proteins (positive effect). The results of our analysis could be used for guiding the search for antiviral drug targets to combat SARS-CoV-2 infection.

show abstract

“…The S protein that is involved attachment to host cells is located on the surface of the viral particles and is highly immunogenic (Huang et al 2020a, b;Dai and Gao 2021). The N protein is a major structural protein of the virus and medicates various functions such as viral assembly and RNA replication (Khan et al 2021;Yadav et al 2021). The N protein is highly immunogenic and is expressed in a high rate during infection (Khan et al 2020;Zeng et al 2020).…”

Section: Discussionmentioning

confidence: 99%

In-silico design of a multi-epitope for developing sero-diagnosis detection of SARS-CoV-2 using spike glycoprotein and nucleocapsid antigens

Mamaghani

Arab-Mazar

Heidarzadeh

et al. 2021

Netw Model Anal Health Inform Bioinforma

View full text Add to dashboard Cite

COVID-19 is a pandemic disease caused by novel corona virus, SARS-CoV-2, initially originated from China. In response to this serious life-threatening disease, designing and developing more accurate and sensitive tests are crucial. The aim of this study is designing a multi-epitope of spike and nucleocapsid antigens of COVID-19 virus by bioinformatics methods. The sequences of nucleotides obtained from the NCBI Nucleotide Database. Transmembrane structures of proteins were predicted by TMHMM Server and the prediction of signal peptide of proteins was performed by Signal P Server. B-cell epitopes' prediction was performed by the online prediction server of IEDB server. Beta turn structure of linear epitopes was also performed using the IEDB server. Conformational epitope prediction was performed using the CBTOPE and eventually, eight antigenic epitopes with high physicochemical properties were selected, and then, all eight epitopes were blasted using the NCBI website. The analyses revealed that α-helices, extended strands, β-turns, and random coils were 28.59%, 23.25%, 3.38%, and 44.78% for S protein, 21.24%, 16.71%, 6.92%, and 55.13% for N Protein, respectively. The S and N protein three-dimensional structure was predicted using the prediction I-TASSER server. In the current study, bioinformatics tools were used to design a multi-epitope peptide based on the type of antigen and its physiochemical properties and SVM method (Machine Learning) to design multi-epitopes that have a high avidity against SARS-CoV-2 antibodies to detect infections by COVID-19.

show abstract

Structures of SARS-CoV-2 RNA-Binding Proteins and Therapeutic Targets

Cited by 48 publications

References 100 publications

Neutralizing antibodies for the prevention and treatment of COVID-19

Neutralizing antibodies for the prevention and treatment of COVID-19

Intracellular Life Cycle Kinetics of SARS-CoV-2 Predicted Using Mathematical Modelling

In-silico design of a multi-epitope for developing sero-diagnosis detection of SARS-CoV-2 using spike glycoprotein and nucleocapsid antigens

Contact Info

Product

Resources

About