Response of vaccination on community transmission of COVID-19: a dynamical approach.

Due to the severity of COVID-19, vaccination campaigns have been or are underway in most parts of the world. In the current circumstances, it is obligatory to examine the response of vaccination on transmission of the SARS-CoV-2 virus when there are many vaccines available. Considering the importance of vaccination, a dynamic model has been proposed to provide an insight in the same direction. A mathematical model has been developed where six population compartments viz. susceptible, infected, vaccinated, home-isolated, hospitalized and recovered population are considered. Moreover, two novel parameters are included in the model to ascertain the effectiveness and speed of the vaccination campaign. Reproduction number and local stability of both the disease-free and endemic equilibrium points are studied to examine the nature of population dynamics. Graphical results for the community stage of COVID-19 infection are simulated and compared with real data to ascertain the validity of our model. The data is then studied to understand the impact of vaccination. These numerical results evidently demonstrate that home isolation and hospitalization should continue for the infected people until the transmission of the virus from person to person reduces sufficiently after completely vaccinating every nation. This model also recommends that all type of prevention measures should still be taken to avoid any type of critical situation due to infection and also reduce the death rate.

Response of vaccination on community transmission of COVID-19: a dynamical approach

Due to the severity of COVID-19, vaccination campaigns have been or are underway in most parts of the world. In the current circumstances, it is obligatory to examine the response of vaccination on transmission of the SARS-CoV-2 virus when there are many vaccines available. Considering the importance of vaccination, a dynamic model has been proposed to provide an insight in the same direction. A mathematical model has been developed where six population compartments viz. susceptible, infected, vaccinated, home-isolated, hospitalized and recovered population are considered. Moreover, two novel parameters are included in the model to ascertain the effectiveness and speed of the vaccination campaign. Reproduction number and local stability of both the disease-free and endemic equilibrium points are studied to examine the nature of population dynamics. Graphical results for the community stage of COVID-19 infection are simulated and compared with real data to ascertain the validity of our model. The data is then studied to understand the impact of vaccination. These numerical results evidently demonstrate that home isolation and hospitalization should continue for the infected people until the transmission of the virus from person to person reduces sufficiently after completely vaccinating every nation. This model also recommends that all type of prevention measures should still be taken to avoid any type of critical situation due to infection and also reduce the death rate.

Immunoinformatics mapping of potential epitopes in SARS-CoV-2 structural proteins.

All approved coronavirus disease 2019 (COVID-19) vaccines in current use are safe, effective, and reduce the risk of severe illness. Although data on the immunological presentation of patients with COVID-19 is limited, increasing experimental evidence supports the significant contribution of B and T cells towards the resolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Despite the availability of several COVID-19 vaccines with high efficacy, more effective vaccines are still needed to protect against the new variants of SARS-CoV-2. Employing a comprehensive immunoinformatic prediction algorithm and leveraging the genetic closeness with SARS-CoV, we have predicted potential immune epitopes in the structural proteins of SARS-CoV-2. The S and N proteins of SARS-CoV-2 and SARS-CoVs are main targets of antibody detection and have motivated us to design four multi-epitope vaccines which were based on our predicted B- and T-cell epitopes of SARS-CoV-2 structural proteins. The cardinal epitopes selected for the vaccine constructs are predicted to possess antigenic, non-allergenic, and cytokine-inducing properties. Additionally, some of the predicted epitopes have been experimentally validated in published papers. Furthermore, we used the C-ImmSim server to predict effective immune responses induced by the epitope-based vaccines. Taken together, the immune epitopes predicted in this study provide a platform for future experimental validations which may facilitate the development of effective vaccine candidates and epitope-based serological diagnostic assays.

Designing of peptide aptamer targeting the receptor-binding domain of spike protein of SARS-CoV-2: an in silico study.

Short synthetic peptide molecules which bind to a specific target protein with a high affinity to exert its function are known as peptide aptamers. The high specificity of aptamers with small-molecule targets (metal ions, dyes and theophylline; ATP) is within 1 pM and 1 µM range, whereas with the proteins (thrombin, CD4 and antibodies) it is in the nanomolar range (which is equivalent to monoclonal antibodies). The recently identified coronavirus (SARS-CoV-2) genome encodes for various proteins, such as envelope, membrane, nucleocapsid, and spike protein. Among these, the protein necessary for the virus to enter inside the host cell is spike protein. The work focuses on designing peptide aptamer targeting the spike receptor-binding domain of SARS-CoV-2. The peptide aptamer has been designed by using bacterial Thioredoxin A as the scaffold protein and an 18-residue-long peptide. The tertiary structure of the peptide aptamer is modeled and docked to spike receptor-binding domain of SARS CoV2. Molecular dynamic simulation has been done to check the stability of the aptamer and receptor-binding domain complex. It was observed that the aptamer binds to spike receptor-binding domain of SARS-CoV-2 in a similar pattern as that of ACE2. The aptamer-receptor-binding domain complex was found to be stable in a 100 ns molecular dynamic simulation. The aptamer is also predicted to be non-antigenic, non-allergenic, non-hemolytic, non-inflammatory, water-soluble with high affinity toward ACE2 than serum albumin. Thus, peptide aptamer can be a novel approach for the therapeutic treatment for SARS-CoV-2.

Targeting SARS CoV2 (Indian isolate) genome with miRNA: An in silico study.

The newly identified SARS CoV2 has become a global pandemic since December 2019. Various researchers are trying to design a vaccine candidate against the virus. On the other hand, another group is focussing on repurposing approved or clinically tested drugs for treatment. However, there is always a search for alternative therapies. Thus, we propose an alternative approach apart from chemotherapy that is the usage of miRNA as novel antisense therapy to cure SARS CoV2 infected patients. To address the objective, miRNAs have been designed by targeting the genome of SARS CoV2 (Indian isolate). First, the open reading frames in the viral genome have been identified, and the proteins encoded by those open reading frames have been predicted. Using computational biology, several miRNAs have been designed and their probability to bind to a viral gene has been predicted. In addition, miRNA target mining in the host cell has been done to rule out the possibility of non-specific binding of the miRNAs. The miRNAs having the highest chances to bind to the viral genome have been converted into pre-miRNAs, and their interaction with dicer endoribonuclease has been studied by molecular docking. Results revealed that the pre-miRNAs interact with the RNAse III 2 domain of dicer. Thus, it is predicted that the pre-miRNAs after delivery to the infected host cell will be processed by dicer to generate mature miRNAs that will target the SARS CoV2 viral genome. Therefore, miRNA therapy can be an alternative approach for the treatment of SARS CoV2 infection.

In silico designing of multi-epitope vaccine construct against human coronavirus infections.

Single stranded RNA viruses were known to cause variety of diseases since many years and are gaining much importance due to pandemic after the identification of a novel corona virus (severe acute respiratory syndrome-coronavirus (SARS-CoV-2)). Seven coronaviruses (CoVs) are known to infect humans and they are OC43 CoV, NL63 CoV, HKU1 CoV, Middle East respiratory syndrome, SARS CoV, and SARS CoV-2. Virus replication weakens the immune system of host thereby altering T-cell count and much of interferon response. Although no vaccine or therapeutic treatment has been approved till now for CoV infection, trials of vaccine against SARS CoV-2 are in progress. One of the epitopes used for vaccine production is of the spike protein on the surface of virus. The work focuses on designing of multi-epitope vaccine construct for treatment of seven human CoV infections using the epitopes present on the spike protein of human CoVs. To address this, immuno-informatics techniques have been employed to design multi-epitope vaccine construct. B- and T-cell epitopes of the spike proteins have been predicted and designed into a multi-epitope vaccine construct. The tertiary structure of the vaccine construct along with the adjuvant has been modelled and the physiochemical properties have been predicted. The multi-epitope vaccine construct has antigenic and non-allergenic property. After validation, refinement and disulphide engineering of the vaccine construct, molecular docking with toll-like receptors (TLRs) have been performed. Molecular dynamics simulation in aqueous environment predicted that the vaccine-TLRs complexes were stable. The vaccine construct is predicted to be able to trigger primary immune response in silico. Communicated by Ramaswamy H. Sarma.