Aptamer-Mediated Antiviral Approaches for SARS-CoV-2.

2020 and 2021 were disastrous years across the world, with the emergence of the severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) virus as a pandemic, which continues to be a top global health issue. There are still many countries and regions struggling to fight coronavirus disease 2019 (COVID-19), and, with the emergence of the various variants of the virus, we are still far from considering this global pandemic over. In addition to having good diagnostic tools and a variety of vaccines with high efficacy, it is of utmost importance to develop effective antiviral drugs or therapies to battle COVID-19. Aptamers known as the next-generation targeting elements can offer promising opportunities in developing antiviral drugs against SARS-CoV-2. This is owing to their high specificity and affinity, making them ideal for targeting ligands and neutralizers to impede both, viral entry and replication or even further enhance the anti-infection effects in the infected host cells. Also, aptamers are extremely attractive as they can be rapidly synthesized and scalable with a lower production cost. This work provides in-depth discussions on the potential of aptamers in therapeutic applications, their mode of action, and current progress on the use of aptamer-based therapies against SARS-CoV-2 and other viruses. The article also discusses the limitations associated with aptamer-based SARS-CoV-2-antiviral therapy with several proposed ideas to resolve them. Lastly, theranostic applications of aptamer nanoformulated dendrimers against viral infections are discussed.

Chapter 5 - Transmission and intervention dynamics of SARS-CoV-2

Infectious pathogens are a threat to global healthcare and the socioeconomic progress of the world. Since December 2019, the world has battled with the 2019-novel coronavirus disease (COVID-19), a zoonotic viral infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has resulted in high rates of infection and deaths across continents. Coronaviruses, due to their genetic nomenclature of being RNA viruses, easily undergo genetic mutation during their replication cycle. This has resulted in several SARS-CoV-2 variants of concern. The current state and what the future of COVID-19 holds for mankind is an unresolved question hanging on. Recently, there has been great improvement in the fight against the COVID-19 pandemic. Vaccines have been developed to reduce the risk of infection. Also, insights from the study of previous coronaviruses and previous pandemics have been helpful in the quick development of different effective vaccines and the deployment of various effective interventions. In this chapter, discussions on the genesis of COVID-19, its transmission, impact, preventive measures, and therapeutic advancements are presented.

Multivalent ACE2 engineering-A promising pathway for advanced coronavirus nanomedicine development.

The spread of coronavirus diseases has resulted in a clarion call to develop potent drugs and vaccines even as different strains appear beyond human prediction. An initial step that is integral to the viral entry into host cells results from an active-targeted interaction of the viral spike (S) proteins and the cell surface receptor, called angiotensin-converting enzyme 2 (ACE2). Thus, engineered ACE2 has been an interesting decoy inhibitor against emerging coronavirus infestation. This article discusses promising innovative ACE2 engineering pathways for current and emerging coronavirus therapeutic development. First, we provide a brief discussion of some ACE2-associated human coronaviruses and their cell invasion mechanism. Then, we describe and contrast the individual spike proteins and ACE2 receptor interactions, highlighting crucial hotspots across the ACE2-associated coronaviruses. Lastly, we address the importance of multivalency in ACE2 nanomedicine engineering and discuss novel approaches to develop and achieve multivalent therapeutic outcomes. Beyond coronaviruses, these approaches will serve as a paradigm to develop new and improved treatment technologies against pathogens that use ACE2 receptor for invasion.

Aptamers as promising nanotheranostic tools in the COVID-19 pandemic era.

The emergence of SARS-COV-2, the causative agent of new coronavirus disease (COVID-19) has become a pandemic threat. Early and precise detection of the virus is vital for effective diagnosis and treatment. Various testing kits and assays, including nucleic acid detection methods, antigen tests, serological tests, and enzyme-linked immunosorbent assay (ELISA), have been implemented or are being explored to detect the virus and/or characterize cellular and antibody responses to the infection. However, these approaches have inherent drawbacks such as nonspecificity, high cost, are characterized by long turnaround times for test results, and can be labor-intensive. Also, the circulating SARS-COV-2 variant of concerns, reduced antibody sensitivity and/or neutralization, and possible antibody-dependent enhancement (ADE) have warranted the search for alternative potent therapeutics. Aptamers, which are single-stranded oligonucleotides, generated artificially by SELEX (Evolution of Ligands by Exponential Enrichment) may offer the capacity to generate high-affinity neutralizers and/or bioprobes for monitoring relevant SARS-COV-2 and COVID-19 biomarkers. This article reviews and discusses the prospects of implementing aptamers for rapid point-of-care detection and treatment of SARS-COV-2. We highlight other SARS-COV-2 targets (N protein, spike protein stem-helix), SELEX augmented with competition assays and in silico technologies for rapid discovery and isolation of theranostic aptamers against COVID-19 and future pandemics. It further provides an overview on site-specific bioconjugation approaches, customizable molecular scaffolding strategies, and nanotechnology platforms to engineer these aptamers into ultrapotent blockers, multivalent therapeutics, and vaccines to boost both humoral and cellular immunity against the virus. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Diagnostic Tools > Biosensing Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Therapeutic Approaches and Drug Discovery > Nanomedicine for Respiratory Disease.

Anti-SARS-CoV-1 and -2 nanobody engineering towards avidity-inspired therapeutics.

In the past two decades, the emergence of coronavirus diseases has been dire distress on both continental and global fronts and has resulted in the search for potent treatment strategies. One crucial challenge in this search is the recurrent mutations in the causative virus spike protein, which lead to viral escape issues. Among the current promising therapeutic discoveries is the use of nanobodies and nanobody-like molecules. While these nanobodies have demonstrated high-affinity interaction with the virus, the unpredictable spike mutations have warranted the need for avidity-inspired therapeutics of potent inhibitors such as nanobodies. This article discusses novel approaches for the design of anti-SARS-CoV-1 and -2 nanobodies to facilitate advanced innovations in treatment technologies. It further discusses molecular interactions and suggests multivalent protein nanotechnology and chemistry approaches to translate mere molecular affinity into avidity.

Engineered Aptamers for Enhanced COVID-19 Theranostics.

INTRODUCTION: The 2019-novel coronavirus disease (COVID-19) is an intractable global health challenge resulting in an aberrant rate of morbidity and mortality worldwide. The mode of entry for SARS-CoV-2 into host cells occurs through clathrin-mediated endocytosis. As part of the efforts to mitigate COVID-19 infections, rapid and accurate detection methods, as well as smart vaccine and drug designs with SARS-CoV-2 targeting capabilities are critically needed. This systematic review aimed to present a good mapping between the structural and functional characteristics of aptamers and their potential applications in COVID-19 theranostics. METHODS: In this study, extensive discussions into the potential development of aptameric systems as robust theranostics for rapid mitigation of the virulent SARS-CoV-2 was made. Information required for this study were extracted from a systematic review of literature in PubMed, SCOPUS, Web of Science (WOS), and other official related reports from reputable organisations. RESULTS: The global burden of COVID-19 pandemic was discussed including the progress in rapid detection, repurposing of existing antiviral drugs, and development of prophylactic vaccines. Aptamers have highly specific and stable target binding characteristics which can be generated and engineered with less complexity for COVID-19 targeted theranostic applications. CONCLUSIONS: There is an urgent need to develop safe innovative biomedical technologies to mitigate the dire impact of COVID-19 on public health worldwide. Research advances into aptameric systems bode well with the fact that they can be engineered for the development of effective and affordable diagnostics, therapeutics and prophylactic vaccines for SARS-CoV-2 and other infectious pathogens.

Biophysical analysis of SARS-CoV-2 transmission and theranostic development via N protein computational characterization.

Recently, SARS-CoV-2 has been identified as the causative factor of viral infection called COVID-19 that belongs to the zoonotic beta coronavirus family known to cause respiratory disorders or viral pneumonia, followed by an extensive attack on organs that express angiotensin-converting enzyme II (ACE2). Human transmission of this virus occurs via respiratory droplets from symptomatic and asymptomatic patients, which are released into the environment after sneezing or coughing. These droplets are capable of staying in the air as aerosols or surfaces and can be transmitted to persons through inhalation or contact with contaminated surfaces. Thus, there is an urgent need for advanced theranostic solutions to control the spread of COVID-19 infection. The development of such fit-for-purpose technologies hinges on a proper understanding of the transmission, incubation, and structural characteristics of the virus in the external environment and within the host. Hence, this article describes the development of an intrinsic model to describe the incubation characteristics of the virus under varying environmental factors. It also discusses on the evaluation of SARS-CoV-2 structural nucleocapsid protein properties via computational approaches to generate high-affinity binding probes for effective diagnosis and targeted treatment applications by specific targeting of viruses. In addition, this article provides useful insights on the transmission behavior of the virus and creates new opportunities for theranostics development.