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1.
Biomedicines ; 10(7)2022 Jun 21.
Article in English | MEDLINE | ID: covidwho-1933970

ABSTRACT

COVID-19 vaccines have been developed to confer immunity against the SARS-CoV-2 infection. Prior to the pandemic of COVID-19 which started in March 2020, there was a well-established understanding about the structure and pathogenesis of previously known Coronaviruses from the SARS and MERS outbreaks. In addition to this, vaccines for various Coronaviruses were available for veterinary use. This knowledge supported the creation of various vaccine platforms for SARS-CoV-2. Before COVID-19 there are no reports of a vaccine being developed in under a year and no vaccine for preventing coronavirus infection in humans had ever been developed. Approximately nine different technologies are being researched and developed at various levels in order to design an effective COVID-19 vaccine. As the spike protein of SARS-CoV-2 is responsible for generating substantial adaptive immune response, mostly all the vaccine candidates have been targeting the whole spike protein or epitopes of spike protein as a vaccine candidate. In this review, we have compiled the immune response to SARS-CoV-2 infection and followed by the mechanism of action of various vaccine platforms such as mRNA vaccines, Adenoviral vectored vaccine, inactivated virus vaccines and subunit vaccines in the market. In the end we have also summarized the various adjuvants used in the COVID-19 vaccine formulation.

2.
Geroscience ; 2022 Jul 13.
Article in English | MEDLINE | ID: covidwho-1930523

ABSTRACT

The ongoing SARS-CoV-2 evolution process has generated several variants due to its continuous mutations, making pandemics more critical. The present study illustrates SARS-CoV-2 evolution and its emerging mutations in five directions. First, the significant mutations in the genome and S-glycoprotein were analyzed in different variants. Three linear models were developed with the regression line to depict the mutational load for S-glycoprotein, total genome excluding S-glycoprotein, and whole genome. Second, the continent-wide evolution of SARS-CoV-2 and its variants with their clades and divergence were evaluated. It showed the region-wise evolution of the SARS-CoV-2 variants and their clustering event. The major clades for each variant were identified. One example is clade 21K, a major clade of the Omicron variant. Third, lineage dynamics and comparison between SARS-CoV-2 lineages across different countries are also illustrated, demonstrating dominant variants in various countries over time. Fourth, gene-wise mutation patterns and genetic variability of SARS-CoV-2 variants across various countries are illustrated. High mutation patterns were found in the ORF10, ORF6, S, and low mutation pattern E genes. Finally, emerging AA point mutations (T478K, L452R, N501Y, S477N, E484A, Q498R, and Y505H), their frequencies, and country-wise occurrence were identified, and the highest event of two mutations (T478K and L452R) was observed.

3.
Travel Med Infect Dis ; 49: 102398, 2022 Jun 29.
Article in English | MEDLINE | ID: covidwho-1907828

ABSTRACT

Presently, monkeypox has emerged in multiple countries with many confirmed cases, posing a global public health threat. A link has been found between air travel and the international spread of infectious diseases including the previous spread of monkeypox. This article highlights the spread of COVID-19 through air travel, and then monkeypox spread from one country to another. Scientists are trying to establish the air travel and monkeypox spread. Any travel link from an endemic country has not been proven yet to describe the rising number of current monkeypox cases in non-endemic countries. Due to the quantification method, the direct link of the diseases with air travel might be difficult to establish. However, we have also developed different statistical models of the confirmed cases and the number of air travelers per year (noted in countries where monkeypox has spread). As there is no direct link, these models might show a probability of an indirect association of air travel. However, more strong evidence is needed in this direction. Although, the sudden appearance of monkeypox cases in multiple countries in a few days demands comprehensive epidemiological investigations, genome sequencing, and phylogenetic analysis of viral isolates to prove the travel link from an endemic country. At the same time, it is also necessary to know the real cause while also exploring any direct and/or indirect travel links between different countries. Similarly, the possibility of any zoonotic event should find out to understand the more about natural animal reservoir(s) for the monkeypox virus, which is unknown until now. However, this report will help researchers for conducting further explorative research and investigations for understanding transmission patterns and guide policymakers to make proactive policies to limit the spread of monkeypox.

4.
Front Immunol ; 13: 801522, 2022.
Article in English | MEDLINE | ID: covidwho-1902971

ABSTRACT

The infective SARS-CoV-2 is more prone to immune escape. Presently, the significant variants of SARS-CoV-2 are emerging in due course of time with substantial mutations, having the immune escape property. Simultaneously, the vaccination drive against this virus is in progress worldwide. However, vaccine evasion has been noted by some of the newly emerging variants. Our review provides an overview of the emerging variants' immune escape and vaccine escape ability. We have illustrated a broad view related to viral evolution, variants, and immune escape ability. Subsequently, different immune escape approaches of SARS-CoV-2 have been discussed. Different innate immune escape strategies adopted by the SARS-CoV-2 has been discussed like, IFN-I production dysregulation, cytokines related immune escape, immune escape associated with dendritic cell function and macrophages, natural killer cells and neutrophils related immune escape, PRRs associated immune evasion, and NLRP3 inflammasome associated immune evasion. Simultaneously we have discussed the significant mutations related to emerging variants and immune escape, such as mutations in the RBD region (N439K, L452R, E484K, N501Y, K444R) and other parts (D614G, P681R) of the S-glycoprotein. Mutations in other locations such as NSP1, NSP3, NSP6, ORF3, and ORF8 have also been discussed. Finally, we have illustrated the emerging variants' partial vaccine (BioNTech/Pfizer mRNA/Oxford-AstraZeneca/BBIBP-CorV/ZF2001/Moderna mRNA/Johnson & Johnson vaccine) escape ability. This review will help gain in-depth knowledge related to immune escape, antibody escape, and partial vaccine escape ability of the virus and assist in controlling the current pandemic and prepare for the next.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/immunology , Mutation/genetics , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/genetics , Antibody Formation , Humans , Immune Evasion , Pandemics , Spike Glycoprotein, Coronavirus/immunology , Vaccination
8.
Aging Dis ; 13(3): 927-942, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1870133

ABSTRACT

Since September 2020, the SARS-CoV-2 variants have gained their dominance worldwide, especially in Kenya, Italy, France, the UK, Turkey, Indonesia, India, Finland, Ireland, Singapore, Denmark, Germany, and Portugal. In this study, we developed a model on the frequency of delta variants across 28 countries (R2= 0.1497), displaying the inheritance of mutations during the generation of the delta variants with 123,526 haplotypes. The country-wise haplotype network showed the distribution of haplotypes in USA (10,174), Denmark (5,637), India (4,089), Germany (2,350), Netherlands (1,899), Sweden (1,791), Italy (1,720), France (1,293), Ireland (1,257), Belgium (1,207), Singapore (1,193), Portugal (1,184) and Spain (1,133). Our analysis shows the highest haplotype in Europe with 84% and the lowest in Australia with 0.00001%. A model of scatter plot was generated with a regression line which provided the estimated rate of mutation, including 24.048 substitutions yearly. Our study concluded that the high global prevalence of the delta variants is due to a high frequency of infectivity, supporting the paradigm shift of the viral variants.

9.
Hum Vaccin Immunother ; 18(5): 2065824, 2022 Nov 30.
Article in English | MEDLINE | ID: covidwho-1860753

ABSTRACT

The emergence of different variants of SARS-CoV-2, including the Omicron (B.1.1.529) variant in November 2021, has resulted in a continuous major health concern at a global scale. Presently, the Omicron variant has spread very rapidly worldwide within a short time period. As the most mutated variant of SARS-CoV-2, Omicron has instilled serious uncertainties on the effectiveness of humoral adaptive immunity generated by COVID-19 vaccination or an active viral infection as well as the protection provided by antibody-based immunotherapies. Amidst such high public health concerns, the need to carry out booster vaccination has been emphasized. Current evidence reveals the importance of incorporating booster vaccination using several vaccine platforms, such as viral vector- and mRNA-based vaccines, as well as other platforms that are under explorative investigations. Further research is being conducted to assess the effectiveness and durability of protection provided by booster COVID-19 vaccination against Omicron and other SARS-CoV-2 variants.


Subject(s)
COVID-19 , Viral Vaccines , COVID-19/prevention & control , COVID-19 Vaccines , Humans , SARS-CoV-2/genetics
13.
Infect Genet Evol ; 101: 105282, 2022 07.
Article in English | MEDLINE | ID: covidwho-1783642

ABSTRACT

BACKGROUND: The massive increase in COVID-19 infection had generated a second wave in India during May-June 2021 with a critical pandemic situation. The Delta variant (B.1.617.2) was a significant factor during the second wave. Conversely, the UK had passed through the crucial phase of the pandemic from November to December 2020 due to B.1.1.7. The study tried to comprehend the pandemic response in the UK and India to the spread of the B.1.1.7 (Alpha, UK) variant and B.1.617.2 (Delta, India) variant. METHODS: This study was performed in three directions to understand the pandemic response of the two emerging variants. First, we served comparative genomics, such as genome sequence submission patterns, mutational landscapes, and structural landscapes of significant mutations (N501Y, D614G, L452R, E484Q, and P681R). Second, we performed evolutionary epidemiology using molecular phylogenetics, scatter plots of the cluster evaluation, country-wise transmission pattern, and frequency pattern. Third, the receptor binding pattern was analyzed using the Wuhan reference strain and the other two variants. RESULTS: The study analyzed the country-wise and region-wise genome sequences and their submission pattern, molecular phylogenetics, scatter plot of the cluster evaluation, country-wise geographical distribution and transmission pattern, frequency pattern, entropy diversity, and mutational landscape of the two variants. The structural pattern was analyzed in the N501Y, D614G L452R, E484Q, and P681R mutations. The study found increased molecular interactivity between hACE2-RBD binding of B.1.1.7 and B.1.617.2 compared to the Wuhan reference strain. Our receptor binding analysis showed a similar indication pattern for hACE2-RBD of these two variants. However, B.1.617.2 offers slightly better stability in the hACE2-RBD binding pattern through MD simulation than B.1.1.7. CONCLUSION: The increased hACE2-RBD binding pattern of B.1.1.7 and B.1.617.2 might help to increase the infectivity compared to the Wuhan reference strain.


Subject(s)
COVID-19 , SARS-CoV-2 , Angiotensin-Converting Enzyme 2 , COVID-19/epidemiology , Genomics , Humans , Mutation , Pandemics , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/metabolism , United Kingdom/epidemiology
14.
Int Immunopharmacol ; 108: 108766, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1778220

ABSTRACT

Hybrid immunity has been accepted as the most robust immunity to fight against SARS-CoV-2. The hybrid immunity against the virus is produced in individuals who have contracted the disease and received the COVID-19 vaccine. This happens due to the cumulative effect of natural and acquired (vaccine) immunity, which provides higher antibody responses compared to natural and vaccine-produced immunity alone. Scientists have noted that it provides about 25 to 100 times higher antibody responses than natural and vaccine-produced immunity alone. Here, we have tried to illustrate the molecular basis of hybrid immunity against various SARS-CoV-2 variants. We have described hybrid immunity under different headings, which are as follows: an overview of hybrid immunity; a comparison between herd immunity and hybrid immunity against SARS-CoV-2; hybrid immunity in different countries; hybrid immunity and different SARS-CoV-2 variants; the molecular basis of hybrid immunity; and hybrid immunity in Indian scenario. India's large population has recovered from SARS-CoV-2, and data shows that over 1000 million of the population received at least one dose of the vaccine. Besides, many infected individuals who have recovered also received at least one dose of the vaccine leading to hybrid immunity with a less severe third wave compared to the first and second waves. Based on the available data, we hypothesize that people's hybrid immunity could be a major cause of the less severe third wave.


Subject(s)
COVID-19 , Viral Vaccines , COVID-19 Vaccines , Humans , SARS-CoV-2
15.
Appl Microbiol Biotechnol ; 105(24): 9035-9045, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1748501

ABSTRACT

The progression of the COVID-19 pandemic has generated numerous emerging variants of SARS-CoV-2 on a global scale. These variants have gained evolutionary advantages, comprising high virulence and serious infectivity due to multiple spike glycoprotein mutations. As a reason, variants are demonstrating significant abilities to escape the immune responses of the host. The D614G mutation in the S-glycoprotein of SARS-CoV-2 variants has shown the most efficient interaction with the ACE2 receptor of the cells. This explicit mutation at amino acid position 614 (aspartic acid-to-glycine substitution) is the prime cause of infection and re-infection. It changes the conformation of RBD and cleavage patterns S-glycoprotein with higher stability, replication fitness, and fusion efficiencies. Therefore, this review aims to provide several crucial pieces of information associated with the D614 mutational occurrence of SARS-CoV-2 variants and their infectivity patterns. This review will also effectively emphasize the mechanism of action of D614G mutant variants, immune escape, and partial vaccine escape of this virus. Furthermore, the viral characteristic changes leading to the current global pandemic condition have been highlighted. Here, we have tried to illustrate a novel direction for future researchers to develop effective therapeutic approaches and counterweight strategies to minimize the spread of COVID-19.Key points• D614G mutation arises within the S-glycoprotein of significant SARS-CoV-2 variants.• The D614G mutation affects infection, re-infection, cleavage patterns of S-glycoprotein, and replication fitness of SARS-CoV-2 variants.• The D614G mutation influences the immunity and partial vaccine escape.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Mutation , Pandemics , Spike Glycoprotein, Coronavirus/genetics
16.
Geroscience ; 44(2): 619-637, 2022 04.
Article in English | MEDLINE | ID: covidwho-1729366

ABSTRACT

The Omicron variant has been detected in nearly 150 countries. We analyzed the mutational landscape of Omicron throughout the genome, focusing the S-glycoprotein. We also evaluated mutations in the antibody-binding regions and observed some important mutations overlapping those of previous variants including N501Y, D614G, H655Y, N679K, and P681H. Various new receptor-binding domain mutations were detected, including Q493K, G496S, Q498R, S477N, G466S, N440K, and Y505H. New mutations were found in the NTD (Δ143-145, A67V, T95I, L212I, and Δ211) including one new mutation in fusion peptide (D796Y). There are several mutations in the antibody-binding region including K417N, E484A, Q493K, Q498R, N501Y, and Y505H and several near the antibody-binding region (S477N, T478K, G496S, G446S, and N440K). The impact of mutations in regions important for the affinity between spike proteins and neutralizing antibodies was evaluated. Furthermore, we examined the effect of significant antibody-binding mutations (K417N, T478K, E484A, and N501Y) on antibody affinity, stability to ACE2 interaction, and possibility of amino acid substitution. All the four mutations destabilize the antibody-binding affinity. This study reveals future directions for developing neutralizing antibodies against the Omicron variant.


Subject(s)
COVID-19 , SARS-CoV-2 , Angiotensin-Converting Enzyme 2 , Antibodies, Neutralizing/genetics , COVID-19/genetics , Glycoproteins/genetics , Humans , Mutation/genetics , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics
18.
Aging Dis ; 12(8): 2173-2195, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1667753

ABSTRACT

Newly emerging significant SARS-CoV-2 variants such as B.1.1.7, B.1.351, and B.1.1.28 are the variant of concern (VOC) for the human race. These variants are getting challenging to contain from spreading worldwide. Because of these variants, the second wave has started in various countries and is threatening human civilization. Thus, we require efficient vaccines that can combat all emerging variants of SARS-CoV-2. Therefore, we took the initiative to develop a peptide-based next-generation vaccine using four variants (Wuhan variant, B.1.1.7, B.1.351, and B.1.1.28) that could potentially combat SARS-CoV-2 variants. We applied a series of computational tools, servers, and software to identify the most significant epitopes present on the mutagenic regions of SARS-CoV-2 variants. The immunoinformatics approaches were used to identify common B cell derived T cell epitopes, influencing the host immune system. Consequently, to develop a novel vaccine candidate, the antigenic epitopes were linked with a flexible and stable peptide linker, and the adjuvant was added at the N-terminal end. 3D vaccine candidate structure was refined, and quality was assessed using web servers. The physicochemical properties and safety parameters of the vaccine construct were assessed through bioinformatics and immunoinformatics tools. The molecular docking analysis between TLR4/MD2 and the proposed vaccine candidate demonstrated a satisfactory interaction. The molecular dynamics studies confirmed the stability of the vaccine candidate. Finally, we optimized the proposed vaccine through codon optimization and in silico cloning to study the expression. Our multi-epitopic next-generation peptide vaccine construct can boost immunity against the Wuhan variant and all significant mutant variants of SARS-CoV-2.

19.
Mol Biotechnol ; 64(5): 510-525, 2022 May.
Article in English | MEDLINE | ID: covidwho-1603883

ABSTRACT

Presently, the world needs safe and effective vaccines to overcome the COVID-19 pandemic. Our work has focused on formulating two types of mRNA vaccines that differ in capacity to copy themselves inside the cell. These are non-amplifying mRNA (NRM) and self-amplifying mRNA (SAM) vaccines. Both the vaccine candidates encode an engineered viral replicon which can provoke an immune response. Hence we predicted and screened twelve epitopes from the spike glycoprotein of SARS-CoV-2. We used five CTL, four HTL, and three B-cell-activating epitopes to formulate each mRNA vaccine. Molecular docking revealed that these epitopes could combine with HLA molecules that are important for boosting immunogenicity. The B-cell epitopes were adjoined with GPGPG linkers, while CTL and HTL epitopes were linked with KK linkers. The entire protein chain was reverse translated to develop a specific NRM-based vaccine. We incorporate gene encoding replicase in the upstream region of CDS encoding antigen to design the SAM vaccine. Subsequently, signal sequences were added to human mRNA to formulate vaccines. Both vaccine formulations translated to produce the epitopes in host cells, initiate a protective immune cascade, and generate immunogenic memory, which can counter future SARS-CoV-2 viral exposures before the onset of infection.


Subject(s)
COVID-19 , SARS-CoV-2 , Bioengineering , COVID-19/prevention & control , COVID-19 Vaccines/genetics , Epitopes, B-Lymphocyte/genetics , Epitopes, T-Lymphocyte/genetics , Humans , Immunogenicity, Vaccine , Molecular Docking Simulation , Pandemics/prevention & control , RNA, Messenger/genetics , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Vaccines, Synthetic , mRNA Vaccines
20.
Front Immunol ; 12: 724936, 2021.
Article in English | MEDLINE | ID: covidwho-1592205

ABSTRACT

The COVID-19 pandemic has created an urgent situation throughout the globe. Therefore, it is necessary to identify the differentially expressed genes (DEGs) in COVID-19 patients to understand disease pathogenesis and the genetic factor(s) responsible for inter-individual variability. The DEGs will help understand the disease's potential underlying molecular mechanisms and genetic characteristics, including the regulatory genes associated with immune response elements and protective immunity. This study aimed to determine the DEGs in mild and severe COVID-19 patients versus healthy controls. The Agilent-085982 Arraystar human lncRNA V5 microarray GEO dataset (GSE164805 dataset) was used for this study. We used statistical tools to identify the DEGs. Our 15 human samples dataset was divided into three groups: mild, severe COVID-19 patients and healthy control volunteers. We compared our result with three other published gene expression studies of COVID-19 patients. Along with significant DEGs, we developed an interactome map, a protein-protein interaction (PPI) pattern, a cluster analysis of the PPI network, and pathway enrichment analysis. We also performed the same analyses with the top-ranked genes from the three other COVID-19 gene expression studies. We also identified differentially expressed lncRNA genes and constructed protein-coding DEG-lncRNA co-expression networks. We attempted to identify the regulatory genes related to immune response elements and protective immunity. We prioritized the most significant 29 protein-coding DEGs. Our analyses showed that several DEGs were involved in forming interactome maps, PPI networks, and cluster formation, similar to the results obtained using data from the protein-coding genes from other investigations. Interestingly we found six lncRNAs (TALAM1, DLEU2, and UICLM CASC18, SNHG20, and GNAS) involved in the protein-coding DEG-lncRNA network; which might be served as potential biomarkers for COVID-19 patients. We also identified three regulatory genes from our study and 44 regulatory genes from the other investigations related to immune response elements and protective immunity. We were able to map the regulatory genes associated with immune elements and identify the virogenomic responses involved in protective immunity against SARS-CoV-2 infection during COVID-19 development.


Subject(s)
COVID-19/genetics , Gene Expression Profiling/methods , Gene Expression Regulation , Immunity/genetics , Aged , COVID-19/epidemiology , COVID-19/immunology , Female , Gene Ontology , Gene Regulatory Networks , Humans , Male , Middle Aged , Pandemics/prevention & control , Protein Interaction Maps/genetics , SARS-CoV-2/immunology , SARS-CoV-2/physiology , Signal Transduction/genetics , Signal Transduction/immunology
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