RESUMO
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19) infection, which has emerged as a global pandemic causing serious concerns. Lack of specific and effective therapeutics for the treatment of COVID-19 is a major concern and the development of vaccines is another important aspect in managing the infection effectively. The first step in the SARS-CoV-2 pathogenesis is the viral entry and it is mediated by its densely glycosylated spike protein (S-protein). Similar to the SARS-CoV, SARS-CoV-2 also engages angiotensin-converting enzyme 2 (ACE2) as the host cell entry receptor. In addition to ACE2, several recent studies have implicated the crucial role of cell surface heparan sulfate (HS) as a necessary assisting cofactor for ACE2-mediated SARS-CoV-2 entry. Furthermore, SARS-CoV-2 was also identified to use both endosomal cysteine proteases cathepsin B and L (CatB/L) and the transmembrane serine protease 2 (TMPRSS2) for the pivotal role of S-protein priming mediating viral entry. As the entry of SARS-CoV-2 into host cells is mandatory for viral infection, it becomes an extremely attractive therapeutic intervention point. In this regard, this review will focus on the therapeutic targeting of the crucial steps of SARS-CoV-2 viral entry like S-protein/ACE2 interaction and S-protein priming by host cell proteases. In addition, this review will also give insights to the readers on several therapeutic opportunities, pharmacological targeting of the viral-entry facilitators like S-Protein, ACE2, cell surface HS, TMPRSS2, and CatB/L and evidence for those drugs currently ongoing clinical studies.
Assuntos
Enzima de Conversão de Angiotensina 2/metabolismo , Tratamento Farmacológico da COVID-19 , COVID-19 , SARS-CoV-2 , Serina Endopeptidases/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo , Internalização do Vírus/efeitos dos fármacos , COVID-19/virologia , Humanos , Ligação Proteica , Receptores Virais/metabolismo , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/fisiologiaRESUMO
The ineffective immunosuppressant's and targeted strategies to neutralize inflammatory mediators have worsened the scenario of heart failure and have opened many questions for debate. Stem cell therapy has proven to be a promising approach for treating heart following myocardial infarction (MI). Adult stem cells, induced pluripotent stem cells and embryonic stem cells are possible cell types and have successfully shown to regenerate damaged myocardial tissue in pre-clinical and clinical studies. Current implications of using mesenchymal stem cells (MSCs) owing to their immunomodulatory functions and paracrine effects could serve as an effective alternative treatment option for rejuvenating the heart post MI. The major setback associated with the use of MSCs is reduced cell retention, engraftment and decreased effectiveness. With a few reports on understanding the role of inflammation and its dual effects on the structure and function of heart, this review focuses on these missing insights and further exemplifies the role of MSCs as an alternative therapy in treating the pathological consequences in myocardial infarction (MI).
Assuntos
Inflamação/patologia , Infarto do Miocárdio/terapia , Miocárdio/patologia , Regeneração , Transplante de Células-Tronco , Animais , Proliferação de Células , Ativação do Complemento , Fibrose , Humanos , Células-Tronco Mesenquimais/citologia , Camundongos , Neutrófilos/citologia , Estresse Oxidativo , Células-Tronco Pluripotentes/citologia , Medicina Regenerativa/métodosRESUMO
Early diagnosis and treatment of parasitic diseases are indispensable to combat parasites mediated morbidity and mortality in humans and animals. Mammalian sourced antibodies are being successfully used in immunotherapy and immunoassays. However, their increased conservation amongst mammals, involves them in unnecessary interaction and immune mediated pathologies, obstructing their applications in certain approaches in immunoassays. Further, the high production cost and difficulty to achieve high and stable antibody titer hampers their utility for therapeutic purposes. In recent years, chicken egg yolk immunoglobulin, termed as immunoglobulin Y (IgY) has attracted noticeable consideration since it poses greater advantages than mammalian IgG including high yield, low cost and convenience. IgY has unique properties which are being exploited in different aspects for its applications in research, diagnosis and therapy. This review gives an overview of the research outcomes pertaining to chicken IgY as diagnostics and therapeutics in parasitology.