Comprehensive Structural and Molecular Comparison of Spike Proteins of SARS-CoV-2, SARS-CoV and MERS-CoV, and Their Interactions with ACE2 (original) (raw)
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2020
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease (COVID-19), is a novel beta coronavirus emerged in China in 2019. Coronavirus uses spike glycoprotein to interact with host angiotensin-converting enzyme 2 (ACE2) and ensure cell recognition. High infectivity of SARS-CoV-2 raises questions on spike-ACE2 binding affinity and its neutralization by anti-SARS-CoV monoclonal antibodies (mAbs). Here, we observed Val-to-Lys417 mutation in the receptor-binding domains (RBD) of SARS-CoV-2, which established a Lys-Asp electrostatic interaction enhancing its ACE2-binding. Pro-to-Ala475 substitution and Gly482 insertion in the AGSTPCNGV-loop of RBD hindered neutralization of SARS-CoV-2 by anti-SARS-CoV mAbs. In addition, we identified unique and structurally conserved conformational-epitopes on RBDs, which can be potential therapeutic targets. Collectively, we provide new insights into the mechanisms underlying the high infectivity of SARS-CoV-2 and d...
2020
SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a novel coronavirus causing an outbreak of COVID-19 globally in the past six months. A relatively higher divergence on the spike protein of SASR-CoV-2 enables it to transmit across species efficiently. We particularly believe that the adaptive mutations of the receptor-binding domain (RBD) of spike protein in SARS-CoV-2 might be essential to its high transmissibility among humans. Thus here we collected 2,142 high-quality genome sequences of SARS-CoV-2 from 160 regions in over 50 countries and reconstructed their phylogeny, and also analyzed the interaction between the polymorphisms of spike protein and human ACE2 (hACE2). Phylogenetic analysis of SARS-CoV-2 and coronavirus in other hosts show SARS-CoV-2 is highly possible originated from Bat-CoV (RaTG13) found in horseshoe bat and a recombination event may occur on the spike protein of Pangolin-CoV to imbue it the ability to infect humans. Moreover, compared to the S g...
bioRxiv, 2020
SARS-CoV-2, the causative agent of COVID-2019 pandemic is an RNA virus prone to mutations. Information on mutations within the circulating strains of the virus is pivotal to understand disease spread and dynamics. Here, we analyse the mutations associated with 2,954 globally reported high quality genomes of SARS-CoV-2 with special emphasis on genomes of viral strains from India. Molecular phylogenetic analysis suggests that SARS-CoV-2 strains circulating in India form five distinct phyletic clades designated R1-R5. These clades categorize into the previously reported S, G as well as a new unclassified subtype. A detailed analysis of gene encoding the Spike (S) protein in the strains across the globe shows non-synonymous mutations on 54 amino acid residues. Among these, we pinpoint 4 novel mutations in the region that interacts with human ACE2 receptor (RBD). Further in silico molecular docking analyses suggest that these RBD mutations could alter the binding affinity of S-protein wi...
JMIR Bioinformatics and Biotechnology
Background A recent global outbreak of COVID-19 caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) created a pandemic and emerged as a potential threat to humanity. The analysis of virus genetic composition has revealed that the spike protein, one of the major structural proteins, facilitates the entry of the virus to host cells. Objective The spike protein has become the main target for prophylactics and therapeutics studies. Here, we compared the spike proteins of SARS-CoV-2 variants using bioinformatics tools. Methods The spike protein sequences of wild-type SARS-CoV-2 and its 6 variants—D614G, alpha (B.1.1.7), beta (B.1.351), delta (B.1.617.2), gamma (P.1), and omicron (B.1.1.529)—were retrieved from the NCBI database. The ClustalX program was used to sequence multiple alignment and perform mutational analysis. Several online bioinformatics tools were used to predict the physiological, immunological, and structural features of the spike proteins of SARS-C...
2020
The spread of the COVID-19 caused by the SARS-CoV-2 outbreak has been growing since its first identification in December 2019. The publishing of the first SARS-CoV-2 genome made a valuable source of data to study the details about its phylogeny, evolution, and interaction with the host. Protein-protein binding assays have confirmed that Angiotensin-converting enzyme 2 (ACE2) is more likely to be the cell receptor via which the virus invades the host cell. In the present work, we provide an insight into the interaction of the viral spike Receptor Binding Domain (RBD) from different coronavirus isolates with host ACE2 protein. By calculating .
In Silico Characterisation of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) based on the Spike Protein Gene T he SARS-CoV-2 (Severe Acute Respiratory Syndrome-Coronavirus-2), the causative agent of COVID-19 is found to be similar to Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) and Severe Acute Respiratory Syndrome-Coronavirus (SARS-CoV). This virus has led to infecting over 223 countries worldwide with over 133 million (133,552,774) confirmed cases and 2 million (2,894,295) confirmed deaths as of World Health Organisation (WHO) reports on 10 th April, 2021. [1] The mortality rate of SARS-CoV-2 lies between 1-35% and is similar to SARS-CoV and MERS-CoV during the year 2003 and 2012 respectively. [2] With a higher infectivity rate than its mortality rate, COVID-19 finds itself easily unfurling across six continents in the form of droplets, sneezing and cough from one individual to another. [3,4] The disease is primarily characterized by fever, sore throat, common cold, fatigue, lack of smell and taste. People having comorbidity such as heart disease, diabetes or chronic lung disease may further develop severe symptoms including pneumonia and acute respiratory distress syndrome. A few people also develop asymptomatic conditions of the disease. [5,6] Objectives: The Coronavirus Disease 2019 (COVID-19) caused by SARS-CoV-2 has been the current global pandemic concern. With a high transmission rate, especially through direct contact, this disease spreads from person to person, and this has in turn led to a huge number of infections on a global scale. Methods: In present study, comparative genomic analysis was performed using 151 gene sequences of the viral spike protein retrieved from NCBI and along with its translated nucleotide sequences using MEGAX software. Variation in the nucleotide and amino acid positions were identified.
Perspective Chapter: Bioinformatics Study of the Evolution of SARS-CoV-2 Spike Protein
Infectious Diseases
SARS-CoV-2 belongs to the family of coronaviruses, which are characterized by spikes that sit densely on the surface of the virus. The spike protein (Spro) is responsible for the attachment of the virus to the host cell via the ACE2 receptor on the surface of the host cell. The strength of the interaction between the receptor-binding domain (RBD) of the highly glycosylated spike protein of the virus and the host cell ACE2 receptor represents the key determinant of the infectivity of the virus. The SARS-CoV-2 virus has mutated since the beginning of the outbreak, and the vast majority of mutations has been detected in the spike protein or its RBD. Since specific mutations significantly affect the ability of the virus to transmit and to evade immune response, studies of these mutations are critical. We investigate GISAID data to show how viral spike protein mutations evolved during the pandemic. We further present the interactions of the viral Spro RBD with the host ACE2 receptor. We ...
SARS-CoV19-2 Spike Protein Mutation Patterns: A Global Scenario
2020
Analysis of SARS-CoV-2 spike protein sequences of over 19 countries from biological databases submitted around the globe was carried out with help of bioinformatics tools and structure prediction databases. Initial data analysis showed entry of virus into different geographic regions started in the month of January 2020. Meanwhile, alignment of spike protein sequences of SARS-CoV-2 isolates from China and other countries revealed a critical mutation of D614G. Surprisingly, mutation D614G was not seen in early samples submitted in the month of January but gradually it started appearing globally from the month of March 2020. However, the mutations of amino acids in the spike protein other than D614G exhibiting similar pI and altered polarity were found to be specific to geographical regions. Besides, prediction of homology model for interaction of spike protein showed predominant role of chain C of trimeric spike protein in adhering receptor binding domain (RBD) of human ACE2 receptor...
Molecules
We analyzed the epitope evolution of the spike protein in 1,860,489 SARS-CoV-2 genomes. The structural dynamics of these epitopes was determined by molecular modeling approaches. The D614G mutation, selected in the first months of the pandemic, is still present in currently circulating SARS-CoV-2 strains. This mutation facilitates the conformational change leading to the demasking of the ACE2 binding domain. D614G also abrogated the binding of facilitating antibodies to a linear epitope common to SARS-CoV-1 and SARS-CoV-2. The main neutralizing epitope of the N-terminal domain (NTD) of the spike protein showed extensive structural variability in SARS-CoV-2 variants, especially Delta and Omicron. This epitope is located on the flat surface of the NTD, a large electropositive area which binds to electronegatively charged lipid rafts of host cells. A facilitating epitope located on the lower part of the NTD appeared to be highly conserved among most SARS-CoV-2 variants, which may repre...
Eurasian Journal of Medicine and Oncology, 2021
In Silico Characterisation of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) based on the Spike Protein Gene T he SARS-CoV-2 (Severe Acute Respiratory Syndrome-Coronavirus-2), the causative agent of COVID-19 is found to be similar to Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) and Severe Acute Respiratory Syndrome-Coronavirus (SARS-CoV). This virus has led to infecting over 223 countries worldwide with over 133 million (133,552,774) confirmed cases and 2 million (2,894,295) confirmed deaths as of World Health Organisation (WHO) reports on 10 th April, 2021. [1] The mortality rate of SARS-CoV-2 lies between 1-35% and is similar to SARS-CoV and MERS-CoV during the year 2003 and 2012 respectively. [2] With a higher infectivity rate than its mortality rate, COVID-19 finds itself easily unfurling across six continents in the form of droplets, sneezing and cough from one individual to another. [3,4] The disease is primarily characterized by fever, sore throat, common cold, fatigue, lack of smell and taste. People having comorbidity such as heart disease, diabetes or chronic lung disease may further develop severe symptoms including pneumonia and acute respiratory distress syndrome. A few people also develop asymptomatic conditions of the disease. [5,6] Objectives: The Coronavirus Disease 2019 (COVID-19) caused by SARS-CoV-2 has been the current global pandemic concern. With a high transmission rate, especially through direct contact, this disease spreads from person to person, and this has in turn led to a huge number of infections on a global scale. Methods: In present study, comparative genomic analysis was performed using 151 gene sequences of the viral spike protein retrieved from NCBI and along with its translated nucleotide sequences using MEGAX software. Variation in the nucleotide and amino acid positions were identified.