scholarly journals An in silico analysis of early SARS-CoV-2 variant B.1.1.529 (Omicron) genomic sequences and their epidemiological correlates

2021 ◽  
Author(s):  
Ashutosh Kumar ◽  
Adil Asghar ◽  
Himanshu N. Singh ◽  
Muneeb A. Faiq ◽  
Sujeet Kumar ◽  
...  
Keyword(s):  
In Silico ◽  
Immune Escape ◽  
Mutational Analysis ◽  
In Silico Analysis ◽  
Spike Protein ◽  
World Health ◽  
Genomic Sequences ◽  
Binding Motif ◽  
New Variant ◽  
Silico Analysis

Background: A newly emerged SARS-CoV-2 variant B.1.1.529 has worried health policymakers worldwide due to the presence of a large number of mutations in its genomic sequence, especially in the spike protein region. World Health Organization (WHO) has designated it as a global variant of concern (VOC) and has named as Omicron. A surge in new COVID-19 cases has been reported from certain geographical locations, primarily in South Africa (SA) following the emergence of Omicron. Materials and methods: We performed an in silico analysis of the complete genomic sequences of Omicron available on GISAID (until 2021-12-6) to predict the functional impact of the mutations present in this variant on virus-host interactions in terms of viral transmissibility, virulence/lethality, and immune escape. In addition, we performed a correlation analysis of the relative proportion of the genomic sequences of specific SARS-CoV-2 variants (in the period of 01 Oct-29 Nov 2021) with the current epidemiological data (new COVID-19 cases and deaths) from SA to understand whether the Omicron has an epidemiological advantage over existing variants. Results: Compared to the current list of global VOCs/VOIs (as per WHO) Omicron bears more sequence variation, specifically in the spike protein and host receptor-binding motif (RBM). Omicron showed the closest nucleotide and protein sequence homology with Alpha variant for the complete sequence as well as for RBM. The mutations were found primarily condensed in the spike region (28-48) of the virus. Further, the mutational analysis showed enrichment for the mutations decreasing ACE2-binding affinity and RBD protein expression, in contrast, increasing the propensity of immune escape. An inverse correlation of Omicron with Delta variant was noted (r=-0.99, p< .001, 95% CI: -0.99 to -0.97) in the sequences reported from SA post-emergence of the new variant, later showing a decrease. There has been a steep rise in the new COVID-19 cases in parallel with the increase in the proportion of Omicron since the first case (74-100%), on the contrary, the incidences of new deaths have not been increased (r=-0.04, p>0.05, 95% CI =-0.52 to 0.58). Conclusions: Omicron may have greater immune escape ability than the existing VOCs/VOIs. However, there are no clear indications coming out from the predictive mutational analysis that the Omicron may have higher virulence/lethality than other variants, including Delta. The higher ability for immune escape may be a likely reason for the recent surge in Omicron cases in SA.

In Silico Analysis of Plant-Derived Medicinal Compounds Against Spike Protein of SARS-CoV-2 and Ace2

2021 ◽  
pp. 299-313
Author(s):  
Tanya Sharma ◽  
Mohammad Nawaid Zaman ◽  
Shazia Rashid ◽  
Seneha Santoshi
Keyword(s):  
In Silico ◽  
In Silico Analysis ◽  
Spike Protein ◽  
Medicinal Compounds ◽  
Silico Analysis

scholarly journals A Review on the Novel Coronavirus Disease based on In-silico Analysis of Various Drugs and Target Proteins

2020 ◽  
Vol 14 (suppl 1) ◽  
pp. 849-860
Author(s):  
Gauravi N. Trivedi ◽  
Janhavi T. Karlekar ◽  
Hiren A. Dhameliya ◽  
Hetalkumar Panchal
Keyword(s):  
In Silico ◽  
Close Contact ◽  
Genome Structure ◽  
In Silico Analysis ◽  
Bioactive Compound ◽  
Host Cells ◽  
World Health ◽  
Large Set ◽  
Genomic Rnas ◽  
Silico Analysis

Coronavirus Disease (COVID-19) is a new disease that emerged in Wuhan, China which spreads through close contact of people, often by small droplets produced during coughing or sneezing. Detail mechanism by which it spreads between people are under investigation. The World Health Organization (WHO) declared this disease as a pandemic after the severity of the disease increased. Many scientific reports gathered have suggested many drugs that could be potential candidates for the treatment. Although, clinical effectiveness has not been fully evaluated. In this review, we have aggregated the data from few research articles, official news websites and few review papers regarding its phylogenetic relation, genomic constitution, transmission, replication and in-silico analysis done by researchers for few potent drugs that are currently used to cure COVID-19. SARS-CoV-2 belongs to Betacoronavirus genus with Genome structure consists 14 Open Reading Frames (ORFs) that encode 27 proteins. Coronavirus replicates into the host cells having unique mechanisms like ribosome frame-shifting and synthesis of genomic and sub genomic RNAs. In-silico methods have the advantage that they can make fast predictions for a large set of compounds in a high-throughput mode and also make their prediction based on the structure of a compound even before it has been synthesized. In-silico softwares have been used to find or to improve a novel bioactive compound, which may exhibit a strong affinity to a particular target in the drug development process.

scholarly journals In Silico Analysis of Honeybee Venom Protein Interaction with Wild Type and Mutant (A82V + P375S) Ebola Virus Spike Protein

Biologics ◽  
2022 ◽  
Vol 2 (1) ◽  
pp. 45-55
Author(s):  
Muhammad Muzammal ◽  
Muzammil Ahmad Khan ◽  
Mohammed Al Mohaini ◽  
Abdulkhaliq J. Alsalman ◽  
Maitham A. Al Hawaj ◽  
...  
Keyword(s):  
Phospholipase A2 ◽  
Strong Interaction ◽  
In Silico ◽  
Ebola Virus ◽  
In Silico Analysis ◽  
Spike Protein ◽  
Honeybee Venom ◽  
Silico Analysis ◽  
Venom Proteins ◽  
Proteins And Peptides

Venom from different organisms was used in ancient times to treat a wide range of diseases, and to combat a variety of enveloped and non-enveloped viruses. The aim of this in silico research was to investigate the impact of honeybee venom proteins and peptides against Ebola virus. In the current in silico study, different online and offline tools were used. RaptorX (protein 3D modeling) and PatchDock (protein–protein docking) were used as online tools, while Chimera and LigPlot + v2.1 were used for visualizing protein–protein interactions. We screened nine venom proteins and peptides against the normal Ebola virus spike protein and found that melittin, MCD and phospholipase A2 showed a strong interaction. We then screened these peptides and proteins against mutated strains of Ebola virus and found that the enzyme phospholipase A2 showed a strong interaction. According to the findings, phospholipase A2 found in honeybee venom may be an effective source of antiviral therapy against the deadly Ebola virus. Although the antiviral potency of phospholipase A2 has been recorded previously, this is the first in silico analysis of honeybee phospholipase A2 against the Ebola viral spike protein and its more lethal mutant strain.

An Extended Coatomer Binding Motif in the SARS-CoV-2 Spike Protein

2021 ◽  
Author(s):  
Debajit Dey ◽  
Suruchi Singh ◽  
Saif Khan ◽  
Matthew Martin ◽  
Nicholas Schnicker ◽  
...  
Keyword(s):  
In Silico Analysis ◽  
Residue Level ◽  
Spike Protein ◽  
Binding Motif ◽  
Binding Assays ◽  
Retrograde Trafficking ◽  
Intermediate Compartment ◽  
Binding Determinants ◽  
Silico Analysis ◽  
Assembly Site

β-Coronaviruses such as SARS-CoV-2 hijack coatomer protein-I (COPI) for spike protein retrograde trafficking to the progeny assembly site in endoplasmic reticulum-Golgi intermediate compartment (ERGIC). However, limited residue-level details are available into how the spike interacts with COPI. Here we identify a novel extended COPI binding motif in the spike that encompasses the canonical K-x-H dibasic sequence. This motif demonstrates selectivity for αCOPI subunit. Guided by an in silico analysis of dibasic motifs in the human proteome, we employ mutagenesis and binding assays to show that the spike motif terminal residues are critical modulators of complex dissociation, which is essential for spike release in ERGIC. αCOPI residues critical for spike motif binding are elucidated by mutagenesis and crystallography and found to be conserved in the zoonotic reservoirs, bats, pangolins, camels, and in humans. Collectively, our investigation on the spike motif identifies key COPI binding determinants with implications for retrograde trafficking.

scholarly journals In Silico Analysis of Forskolin as a Potential Inhibitor of SARS-CoV-2

2021 ◽  
Author(s):  
Arti Kumari ◽  
Prashant Kumar ◽  
Manindra Kumar ◽  
Jainendra Kumar
Keyword(s):  
In Silico ◽  
Antiviral Agent ◽  
In Silico Analysis ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Health Crisis ◽  
In Silico Docking ◽  
Protein Protein Interaction ◽  
Global Pandemic ◽  
Silico Analysis

Coronavirus disease 2019 (COVID–19) has spread rapidly as global pandemic affecting 187 countries/ regions and emerged as worldwide health crisis. Potential antiviral drugs used for the SARS -CoV-2 in clinical treatments have side effects. However, emergency vaccines are in use but despite that increase in the coronavirus cases are alarming. Thus, it is utmost need of safer antiviral agent to treat or inhibit the viral infection. Forskolin has been reported as a possible antiviral-agent. This molecule was docked with ACE2 receptor of human which is the target for the binding of S1 unit of viral S protein of SARS-CoV- 2. In silico docking was carried out on SwissDock, PatchDock and FireDock servers. The docked ACE2 structure was further docked with the RBD of the spike protein. Forskolin is able to H-bond with the hACE2 and ACE2-forskolin fails to interact with the receptor-binding domain (RBD) of the Spike protein of SARS-CoV-2. Instead, viral RBD is repulsed by the diterpene molecule through obliteration and reciprocated binding. We report first that forskolin plays a crucial role in the inhibition of protein-protein interaction of RBD and ACE2 when docked with either of the protein.

scholarly journals Sea Urchin Pigments as Potential Therapeutic Agents Against the Spike Protein of SARS-CoV-2 Based on in Silico Analysis

2020 ◽  
Author(s):  
Elena Susana Barbieri ◽  
Tamara Rubilar ◽  
Ayelén Gázquez ◽  
Marisa Avaro ◽  
Erina Noé Seiler ◽  
...  
Keyword(s):  
Sea Urchin ◽  
In Silico ◽  
In Silico Analysis ◽  
Protein S ◽  
Host Cells ◽  
Spike Protein ◽  
Therapeutic Drug ◽  
The Novel ◽  
Novel Coronavirus ◽  
Silico Analysis

Several studies have been published regarding the interaction between the spike protein of the novel coronavirus SARS-CoV-2 and ACE2 receptor in the host cells. In the presente work, we evaluated the in silico properties of two sea urchin pigments, Echinochrome A (EchA) and Spinochromes (SpinA) against the Spike protein (S) towards finding a potential therapeutic drug against the disease caused by the novel coronavirus (COVID-19). The best ensemble docking pose of EchaA and SpinA showed a binding affinity of -5.9 and -6.7 kcal mol-1, respectively. The linked aminoacids (T505, G496 and Y449 for EchA and Y449, Q493 and G496 for SpinA) are in positions involved in ACE2 binding in both RBDs frim SARS-CoV and SARS-CoV-2 suggesting that EchA and SpinA may interact with Spike proteins drom both viruses. The results suggest that these pigments could act as inhibitors of S protein, pointing them as antiviral drugs for SARS-CoV-2.<br>

scholarly journals Prediction of SARS-CoV-2 Omicron Variant Immunogenicity, Immune Escape and Pathogenicity, through Analysis of Spike Protein-specific Core Unique Peptides

2021 ◽  
Author(s):  
Vasileios Pierros ◽  
EVANGELOS KONTOPODIS ◽  
DIMITRIOS J. STRAVOPODIS ◽  
GEORGE TH. TSANGARIS
Keyword(s):  
Amino Acids ◽  
Immune Escape ◽  
Contact Point ◽  
Point Mutations ◽  
Spike Protein ◽  
Binding Motif ◽  
Global Awareness ◽  
Virus Binding ◽  
Viral Binding ◽  
New Variant

The recently discovered Omicron variant of the SARS-CoV-2 corona virus has raised a new, global, awareness, since it is considered as a new variant of concern from all major health organizations, including WHO and ECDC. Omicron variant is characterized by 30 amino acid changes, three small deletions and one small insertion in the Spike protein. In this study, we have identified the Core Unique Peptides (CrUPs) that reside exclusively in the Omicron variant of Spike protein and are absent from the human proteome, thus creating a new dataset of peptides named as C/H-CrUPs. Furthermore, we have analyzed their protein locations and compared them with the respective ones of Alpha and Delta SARS-CoV-2 variants. In Omicron, 115 C/H-CrUPs were generated and 119 C/H-CrUPs were lost, almost four times as many compared to the other two variants. From position 440 to position 508, at the Receptor Binding Motif (RBM), 8 mutations were detected, resulting in the construction of 28 novel C/H-CrUPs. Most importantly, in Omicron variant, new C/H-CrUPs carrying two or three mutant amino acids were produced, as a consequence of the accumulation of multiple mutations in the RBM. Remarkably, these Omicron-derived C/H-CrUPs that bear several mutated amino acids could not be recognized in any other viral Spike variant. We suggest that virus binding to the ACE2 receptor is facilitated by the herein identified C/H-CrUPs in contact point mutations and Spike-cleavage sites, while the immunoregulatory NF9 peptide is not detectably affected. Taken together, our findings indicate that Omicron variant contains intrinsic abilities to escape immune-system attack, while its mutations can mediate strong viral binding to the ACE2 receptor, leading to highly efficient fusion of the virus to the target cell. However, the intact NF9 peptide suggests that Omicron exhibits reduced pathogenicity compared to Delta variant.

Sign in / Sign up

Export Citation Format

Share Document