Computational design of a broad-spectrum multi-epitope vaccine candidate against seven strains of human coronaviruses.

Spike (S) proteins are an attractive target as it mediates the binding of the SARS-CoV-2 to the host through ACE-2 receptors. We hypothesize that the screening of the S protein sequences of all the seven known HCoVs would result in the identification of potential multi-epitope vaccine candidates capable of conferring immunity against various HCoVs. In the present study, several machine learning-based in-silico tools were employed to design a broad-spectrum multi-epitope vaccine candidate targeting the S protein of seven known strains of human coronaviruses. Herein, multiple B-cell epitopes and T-cell epitopes (CTL and HTL) were predicted from the S protein sequences of all seven known HCoVs. Post-prediction they were linked together with an adjuvant to construct a potential broad-spectrum vaccine candidate. Secondary and tertiary structures were predicted and validated, and the refined 3D-model was docked with an immune receptor. The vaccine candidate was evaluated for antigenicity, allergenicity, solubility, and its ability to achieve high-level expression in bacterial hosts. Finally, the immune simulation was carried out to evaluate the immune response after three vaccine doses. The designed vaccine is antigenic (with or without the adjuvant), non-allergenic, binds well with TLR-3 receptor and might elicit a diverse and strong immune response. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03286-0.

A comprehensive account of SARS-CoV-2 genome structure, incurred mutations, lineages and COVID-19 vaccination program.

This review collates information on the onset of COVID-19, SARS-CoV-2 genome architecture, emergence of novel viral lineages that drove multiple waves of infection around the world and standard and fast track development of vaccines. With the passage of time, the continuously evolving SARS-CoV-2 has acquired an expanded mutational landscape. The functional characterization of spike protein mutations, the primary target of diagnostics, therapeutics and vaccines has revealed increased transmission, pathogenesis and immune escape potential in the variant lineages of the virus. The incurred mutations have also resulted in substantial viral neutralization escape to vaccines, monoclonal, polyclonal and convalescent antibodies presently in use. The present situation suggests the need for development of precise next-generation vaccines and therapeutics by targeting the more conservative genomic viral regions for providing adequate protection.

Computational design of a broad-spectrum multi-epitope vaccine candidate against seven strains of human coronaviruses

Spike (S) proteins are an attractive target as it mediates the binding of the SARS-CoV-2 to the host through ACE-2 receptors. We hypothesize that the screening of the S protein sequences of all the seven known HCoVs would result in the identification of potential multi-epitope vaccine candidates capable of conferring immunity against various HCoVs. In the present study, several machine learning-based in-silico tools were employed to design a broad-spectrum multi-epitope vaccine candidate targeting the S protein of seven known strains of human coronaviruses. Herein, multiple B-cell epitopes and T-cell epitopes (CTL and HTL) were predicted from the S protein sequences of all seven known HCoVs. Post-prediction they were linked together with an adjuvant to construct a potential broad-spectrum vaccine candidate. Secondary and tertiary structures were predicted and validated, and the refined 3D-model was docked with an immune receptor. The vaccine candidate was evaluated for antigenicity, allergenicity, solubility, and its ability to achieve high-level expression in bacterial hosts. Finally, the immune simulation was carried out to evaluate the immune response after three vaccine doses. The designed vaccine is antigenic (with or without the adjuvant), non-allergenic, binds well with TLR-3 receptor and might elicit a diverse and strong immune response. Supplementary Information The online version contains supplementary material available at 10.1007/s13205-022-03286-0.

Clinically available/under trial drugs and vaccines for treatment of SARS-COV-2

Prior 2019 to work date entire world is seriously influenced by an appalling illness called COVID sickness [Coronavirus disease-2019 (COVID-19)] which is brought about by another strain of coronavirus known as severe acute respiratory syndrome-Coronavirus-2. This pandemic was first seen in the Hubei area in Wuhan city of China. To date above 170 million individuals have been influenced by this infection and more than 3 million individuals died. The race of finding specific therapeutic drugs and efficacious vaccine candidates is still going on to tackle the pandemic-associated morbidities. This chapter discussed different clinically accessible medications (remdesivir, hydroxychloroquine, azithromycin, etc.) and immunizations (mRNA-1273, Sputanik, Pfizer, etc.) which are either in use or under trial for the treatment of COVID-19.

A comprehensive account of SARS-CoV-2 genome structure, incurred mutations, lineages and COVID-19 vaccination program

This review collates information on the onset of COVID-19, SARS-CoV-2 genome architecture, emergence of novel viral lineages that drove multiple waves of infection around the world and standard and fast track development of vaccines. With the passage of time, the continuously evolving SARS-CoV-2 has acquired an expanded mutational landscape. The functional characterization of spike protein mutations, the primary target of diagnostics, therapeutics and vaccines has revealed increased transmission, pathogenesis and immune escape potential in the variant lineages of the virus. The incurred mutations have also resulted in substantial viral neutralization escape to vaccines, monoclonal, polyclonal and convalescent antibodies presently in use. The present situation suggests the need for development of precise next-generation vaccines and therapeutics by targeting the more conservative genomic viral regions for providing adequate protection.

Mapping of SARS-CoV-2 spike protein evolution during first and second waves of COVID-19 infections in India.

Aim: The aim of this study was to investigate the SARS-CoV-2 spike protein evolution during the first and second wave of COVID-19 infections in India. Materials & Methods: Detailed mutation analysis was done in 763 samples taken from GISAID for the ten most affected Indian states between March 2020 to August 2021. Results: The study revealed 242 mutations corresponding to 207 sites. Fifty one novel mutations emerged during the assessment period, including many with higher transmissibility and immune evasion functions. Highest number of mutations per spike protein also rose from 5 (first wave) to 13 (second wave). Conclusion: The study identified mutation-rich and no mutation regions in the spike protein. The conserved spike regions can be useful for designing future diagnostics, vaccines and therapeutics.

Microfluidics-Based Point-of-Care Testing (POCT) Devices in Dealing with Waves of COVID-19 Pandemic: The Emerging Solution.

Recent advances in microfluidics-based point-of-care testing (POCT) technology such as paper, array, and beads have shown promising results for diagnosing various infectious diseases. The fast and timely detection of viral infection has proven to be a critical step for deciding the therapeutic outcome in the current COVID-19 pandemic, which in turn not only enhances the patient survival rate but also reduces the disease-associated comorbidities. In the present scenario, rapid, noninvasive detection of the virus using low cost and high throughput microfluidics-based POCT devices embraces the advantages over existing diagnostic technologies, for which a centralized lab facility, expensive instruments, sample pretreatment, and skilled personnel are required. Microfluidic-based multiplexed POCT devices can be a boon for clinical diagnosis in developing countries that lacks a centralized health care system and resources. The microfluidic devices can be used for disease diagnosis and exploited for the development and testing of drug efficacy for disease treatment in model systems. The havoc created by the second wave of COVID-19 led several countries' governments to the back front. The lack of diagnostic kits, medical devices, and human resources created a huge demand for a technology that can be remotely operated with single touch and data that can be analyzed on a phone. Recent advancements in information technology and the use of smartphones led to a paradigm shift in the development of diagnostic devices, which can be explored to deal with the current pandemic situation. This review sheds light on various approaches for the development of cost-effective microfluidics POCT devices. The successfully used microfluidic devices for COVID-19 detection under clinical settings along with their pros and cons have been discussed here. Further, the integration of microfluidic devices with smartphones and wireless network systems using the Internet-of-things will enable readers for manufacturing advanced POCT devices for remote disease management in low resource settings.

"Is Omicron mild"? Testing this narrative with the mutational landscape of its three lineages and response to existing vaccines and therapeutic antibodies.

SARS-CoV-2 Omicron with its lineages BA.1, BA.2, and BA.3 has triggered a fresh wave of Covid-19 infections. Though, Omicron has, so far, produced mild symptoms, its genome contains 60 mutations including 37 in the spike protein and 15 in the receptor-binding domain. Thirteen sites conserved in previous SARS-CoV-2 variants carry mutations in Omicron. Many mutations have shown evolution under positive selection. Omicron's giant mutational leap has raised concerns as there are signs of higher virus infectivity rate, pathogenesis, reinfection, and immune evasion. Preliminary studies have reported waning of immunity after two-dose primary vaccine regime, need for the boosters, folds reduction in vaccine effectiveness and neutralizing antibodies even after boosting and significant neutralization resistance with the therapeutic monoclonal, polyclonal, and convalescent antibodies against Omicron. The narrative that "Omicron is mild," therefore, needs time to be tested with a deeper, scientific dwelling into the facts.