Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of the coronavirus disease 2019 (COVID-19) pandemic, which has been a topic of major concern for global human health. The challenge to restrain the COVID-19 pandemic is further compounded by the emergence of several SARS-CoV-2 variants viz. B.1.1.7 (Alpha), B.1.351 (Beta), P1 (Gamma) and B.1.617.2 (Delta), which show increased transmissibility and resistance towards vaccines and therapies. Importantly, there is convincing evidence of increased susceptibility to SARS-CoV-2 infection among individuals with dysregulated immune response and comorbidities. Herein, we provide a comprehensive perspective regarding vulnerability of SARS-CoV-2 infection in patients with underlying medical comorbidities. We discuss ongoing vaccine (mRNA, protein-based, viral vector-based, etc.) and therapeutic (monoclonal antibodies, small molecules, plasma therapy, etc.) modalities designed to curb the COVID-19 pandemic. We also discuss in detail, the challenges posed by different SARS-CoV-2 variants of concern (VOC) identified across the globe and their effects on therapeutic and prophylactic interventions.
Project description:Viral variants of concern may emerge with dangerous resistance to the immunity generated by the current vaccines to prevent coronavirus disease 2019 (Covid-19). Moreover, if some variants of concern have increased transmissibility or virulence, the importance of efficient public health measures and vaccination programs will increase. The global response must be both timely and science based.
Project description:Unlike conventional Coronavirus 2019 (COVID-19) vaccines, intranasal vaccines display a superior advantage because the nasal mucosa is often the initial site of infection. Preclinical and clinical studies concerning intranasal immunization elicit high neutralizing antibody generation and mucosal IgA and T cell responses that avoid severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in both; the upper and lower respiratory tract. A nasal formulation is non-invasive with high appeal to patients. Intranasal vaccines enable self-administration and can be designed to survive at ambient temperatures, thereby simplifying logistical aspects of transport and storage. In this review, we provide an overview of nasal vaccines with a focus on formulation development as well as ongoing preclinical and clinical studies for SARS-CoV-2 intranasal vaccine products.
Project description:The ongoing coronavirus disease 2019 (COVID-19) outbreak in Wuhan, China, was triggered and unfolded quickly throughout the globe by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The new virus, transmitted primarily through inhalation or contact with infected droplets, seems very contagious and pathogenic, with an incubation period varying from 2 to 14 days. The epidemic is an ongoing public health problem that challenges the present global health system. A worldwide social and economic stress has been observed. The transitional source of origin and its transport to humans is unknown, but speedy human transportation has been accepted extensively. The typical clinical symptoms of COVID-19 are almost like colds. With case fatality rates varying from 2 to 3 percent, a small number of patients may experience serious health problems or even die. To date, there is a limited number of antiviral agents or vaccines for the treatment of COVID-19. The occurrence and pathogenicity of COVID-19 infection are outlined and comparatively analyzed, given the outbreak's urgency. The recent developments in diagnostics, treatment, and marketed vaccine are discussed to deal with this viral outbreak. Now the scientist is concerned about the appearance of several variants over the globe and the efficacy of the vaccine against these variants. There is a need for consistent monitoring of the virus epidemiology and surveillance of the ongoing variant and related disease severity.
Project description:Since September 2020, the world has had more than 28 million cases of coronavirus disease 2019 (COVID-19). Many countries are facing a second wave of the COVID-19 outbreak. A pressing need is evident for the development of a potent vaccine to control the SARS-CoV-2. Institutions and companies in many countries have announced their vaccine research programs and progress against the COVID-19. While most vaccines go through the designation and preparation stages, some of them are under evaluation for efficacy among animal models and clinical trials, and three approved vaccine candidates have been introduced for limited exploitation in Russia and China. An effective vaccine must induce a protective response of both cell-mediated and humoral immunity and should meet the safety and efficacy criteria. Although the emergence of new technologies has accelerated the development of vaccines, there are several challenges on the way, such as limited knowledge about the pathophysiology of the virus, inducing humoral or cellular immunity, immune enhancement with animal coronavirus vaccines, and lack of an appropriate animal model. In this review, we firstly discuss the immune responses against SARS-CoV-2 disease, subsequently, give an overview of several vaccine platforms for SARS-CoV-2 under clinical trials and challenges in vaccine development against this virus.
Project description:Coronavirus disease 2019 (COVID-19) pandemic is a serious threat to global public health and social and economic development. Various vaccine platforms have been developed rapidly and unprecedentedly, and at least 16 vaccines receive emergency use authorization (EUA). However, the causative pathogen severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has continued to evolve and mutate, emerging lots of viral variants. Several variants have successfully become the predominant strains and spread all over the world because of their ability to evade the pre-existing immunity obtained after previous infections with prototype strain or immunizations. Here, we summarized the prevalence and biological structure of these variants and the efficacy of currently used vaccines against the SARS-CoV-2 variants to provide guidance on how to design vaccines more rationally against the variants.
Project description:The rapid and remarkably successful development, manufacture, and deployment of several effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines is now tempered by three key challenges. First, reducing virus transmission will require prevention of asymptomatic and mild infections in addition to severe symptomatic infections. Second, the emergence of variants of concern with mutations in the S protein's receptor binding domain increases the likelihood that vaccines will have to be updated because some of these mutations render variants less optimally targeted by current vaccines. This will require coordinated global SARS-CoV-2 surveillance to link genotypes to phenotypes, potentially using the WHO's global influenza surveillance program as a guide. Third, concerns about the longevity of vaccine-induced immunity highlight the potential need for re-vaccination, depending on the extent to which the virus has been controlled and whether re-vaccination can target those at greatest risk of severe illness. Fortunately, as I discuss in this review, these challenges can be addressed.
Project description:COVID-19 pandemic caused by SARS-CoV-2 globally impacted the humanity causing tragic outcomes; costing millions of lives, destroying economies and demolishing public health infrastructures. The emergence of vaccines using various ingenious approaches in less than a year was deemed the light at the end of the tunnel. However, recent emergence of variants of SARS-CoV-2 in several parts of the world revealed that another hurdle is ahead in the fight against COVID-19. This review will highlight how SARS-CoV-2 mutations, creating different virus variants could potentially impact virus pathogenesis as well as different therapy approaches and vaccine design.
Project description:In the years since the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic began and spread across the globe, lessons have been learned about the challenges and opportunities that a pandemic brings to humankind. Researchers have produced many vaccines at unprecedented speed to protect people, but they have also been cognizant of the challenges presented by a new and unexpected infectious disease. The scope of this review is to examine the path of vaccine discovery so far and identify potential targets. Here, we provide insight into the leading vaccines and their advantages and challenges. We discuss the emerging mutations within the SARS-CoV-2 spike protein and other issues that need to be addressed to overcome coronavirus disease 2019 (COVID-19) completely. Future research is needed to develop a cheap, temperature-stable vaccine providing long-term immunity that protects the upper respiratory tract.
Project description:ACE2 on epithelial cells is the SARS-CoV-2 entry receptor. Single-cell RNA-sequencing data derived from two COVID-19 cohorts revealed that MAP4K3/GLK-positive epithelial cells were increased in patients. SARS-CoV-2-induced GLK overexpression in epithelial cells correlated with COVID-19 severity and vesicle secretion. GLK overexpression induced the epithelial cell-derived exosomes containing ACE2; the GLK-induced exosomes transported ACE2 proteins to recipient cells, facilitating pseudovirus infection. Consistently, ACE2 proteins were increased in the serum exosomes from another COVID-19 cohort. Remarkably, SARS-CoV-2 spike protein stimulated GLK, and GLK stabilized ACE2 in epithelial cells. Mechanistically, GLK phosphorylated ACE2 at two serine residues (Ser776, Ser783), leading to dissociation of ACE2 from its E3 ligase UBR4. Reduction of UBR4-induced Lys48-linked ubiquitination at three lysine residues (Lys26, Lys112, Lys114) of ACE2 prevented its degradation. Furthermore, SARS-CoV-2 pseudovirus or live virus infection in humanized ACE2 mice induced GLK and ACE2 protein levels, as well as ACE2-containing exosomes. Collectively, ACE2 stabilization by SARS-CoV-2-induced MAP4K3/GLK may contribute to the pathogenesis of COVID-19.