RESUMEN
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of coronavirus induced disease-2019 (COVID-19), is a type of common cold virus responsible for a global pandemic which requires immediate measures for its containment. India has the world's largest population aged between 10 and 40 years. At the same time, India has a large number of individuals with diabetes, hypertension and kidney diseases, who are at a high risk of developing COVID-19. A vaccine against the SARS-CoV-2, may offer immediate protection from the causative agent of COVID-19, however, the protective memory may be short-lived. Even if vaccination is broadly successful in the world, India has a large and diverse population with over one-third being below the poverty line. Therefore, the success of a vaccine, even when one becomes available, is uncertain, making it necessary to focus on alternate approaches of tackling the disease. In this review, we discuss the differences in COVID-19 death/infection ratio between urban and rural India; and the probable role of the immune system, co-morbidities and associated nutritional status in dictating the death rate of COVID-19 patients in rural and urban India. Also, we focus on strategies for developing masks, vaccines, diagnostics and the role of drugs targeting host-virus protein-protein interactions in enhancing host immunity. We also discuss India's strengths including the resources of medicinal plants, good food habits and the role of information technology in combating COVID-19. We focus on the Government of India's measures and strategies for creating awareness in the containment of COVID-19 infection across the country.
RESUMEN
BACKGROUND: The pathobiology of atopic asthma is complex and the symptoms similar to other respiratory diseases. As such, identification of biomarkers of atopic asthma is of prime importance for better diagnosis and control of the disease. OBJECTIVES: We sought to study the changes in plasma proteome and cytokine-expression profile across healthy and atopic asthmatics for identifying biomarkers and exploring aberrant pathways for atopic asthma. METHODS: A pilot-scale study in humans was performed to identify differentially expressed proteins in blood plasma of healthy controls (n=5) and treatment-naïve atopic asthma patients (n=5) using quantitative label-free liquid chromatography-tandem mass spectrometry proteomics and ELISA. RESULTS: Mass spectrometry-based proteomic analysis revealed ApoE to be significantly downregulated in atopic asthmatics compared to healthy volunteers. Decreased expression of ApoE in atopic asthmatics was validated by immunoblotting (50.74% decrease). Comparison with atopic asthmatics and COPD patients showed that ApoE was decreased (36.33%) in atopic asthma compared to COPD. IL33 was significantly upregulated in atopic asthmatics compared to healthy subjects (3.84-fold). CONCLUSION: ApoE was downregulated and IL33 upregulated in atopic asthma patients compared to healthy volunteers. These two proteins' profiles were distinct in atopic asthma from healthy and COPD plasma samples. Differential expression of these proteins could serve as a probable candidate for a two-protein classifier-based prognostic biomarker of atopic asthma.
RESUMEN
Asthma is a complex, heterogeneous, airway inflammatory disorder broadly classified into atopic (IgE mediated) and non-atopic asthma. Monoclonal Antibodies (MAbs) and small chemical Protein- Protein Interaction Modulators (PPIMs) are targeted against interleukins (ILs), which play a critical role in asthma. Many MAbs are targeted against ILs and IgE. Anti IgE MAb (Omalizumab) and Anti IL- 5 MAbs (Mepolizumab, Reslizumab) have only been approved by FDA. Most of the MAbs including Tracolizumab, Lebrikizumab, Anrukinzumab (Anti IL-13 MAb), and Brodalumab (Anti IL-17 MAb) are in different phases of clinical trials. Pascolizumab (Anti IL-4 MAb), however, has failed. These MAbs are expensive and may render adverse immune response. Thus, small chemical modulators targeting ILs and their receptors (IL-Rs) are being exploited computationally and further validated experimentally. The complex ILs and IL-Rs available in PDB are best suited for these types of studies. A large number of small chemical modulators against Protein-Protein Interactions (PPIs) have been compiled in a few databases like TIMBAL, 2P2I DB and IPPIDB. Small chemical libraries are used for virtual screening to find novel modulators targeting IL-R binding interface on IL. Molecular dynamic simulations have been further used for disruption mechanism and kinetic studies. IL-2/IL-2R was targeted with clinically tested small molecule modulators like SP4206, and IL-2 levels were known to increase in non-atopic asthma. In the absence of experimentally known modulators against atopic asthma, computational tools are being explored. For example, IL-33 is a target for atopic asthma where IL-33 and its receptor complex structure is available in PDB. In summary, small chemical modulators against ILs are a complementary approach to MAbs and computational tools have been used for identifying these modulators for asthma.