Coronavirus disease, COVID-19, has touched every country globally except five countries (North Korea, Turkmenistan, Tonga, Tuvalu and Nauru). Vaccination is the most effective method to protect against infectious diseases. The objective is to ensure that everyone has access to a COVID-19 vaccine. The conventional vaccine development platforms are complex and time-consuming to obtain desired approved vaccine candidates through rigorous regulatory pathways. These safeguards guarantee that the optimized vaccine product is safe and efficacious for various demographic populations prior to it being approved for general use. Nucleic acid vaccines employ genetic material from a pathogen, such as a virus or bacteria, to induce an immune response against it. Based on the vaccination, the genetic material might be DNA or RNA; as such, it offers instructions for producing a specific pathogen protein that the immune system will perceive as foreign and mount an immune response. Nucleic acid vaccines for multiple antigens might be made in the same facility, lowering costs even more. Most traditional vaccine regimens do not allow for this. Herein, we demonstrate the recent understanding and advances in nucleic acid vaccines (DNA and mRNA based) against COVID-19, specifically those in human clinical trials.

Asthma is chronic and multi-factorial inflammatory disease hence single allergen induced asthma in an animal is not identical to clinical asthma. Therefore, we developed a novel experimental model of asthma in rats using ovalbumin (OVA) and lipopolysaccharide (LPS) allergens. Rats were divided into four groups; normal (NC), OVA, LPS, and OVA-LPS treated. Rats were sensitized with OVA (100 μg/kg, adsorbed in 100 mg/mL aluminum hydroxide, i.p.), LPS (10 μg/kg, i.p.) and both (OVA-LPS) on 7th, 14th, 21st days and was followed by challenge with OVA (1%w/v), LPS (1%w/v), OVA (0.5%w/v) and LPS (0.5%w/v) for 30 min thrice/week for three weeks in the OVA, LPS and OVA-LPS groups, respectively. On 41 day, lung function parameters (respiration rate, tidal volume, and airflow rate), total and differential leukocytes count in the blood as well as BALf and inflammatory cytokines (IL-4, IL-5, and IL-13) in serum were measured. Histology of lungs was performed.The results suggested that the tidal volume and airflow rate were significantly decreased while respiration rate, total and differential leukocytes count in blood as well as BALf and serum cytokines level were significantly increased in the OVA-LPS as compared to NC, OVA, and LPS.In conclusion, the combination of OVA and LPS induced phenotypes of severe asthma with eosinophilic, neutrophilic and lymphocytic inflammation.

Toll-like receptor-4 (TLR4) is a key component of the innate immune system and activation of TLR4 signaling has a significant role in the pathogenesis of asthma. Therefore, our objective was to identify the natural TLR4 antagonist and evaluate its activity in experimentally induced asthma. Soya lecithin origin phosphatidylcholine (soya PC) was identified as a natural TLR4 antagonist by computational study. Based on the computational study, TLR4 antagonist activity of soya PC was confirmed in in vitro lipopolysaccharide (LPS)-induced neutrophil adhesion assay. In the in vivo study, rats were sensitized with ovalbumin (OVA) (100 μg/kg, i.p.) on the 7th, 14th and 21st days and challenged intranasally with OVA (100 μg/100 μL) and LPS (10 ng/100 μL), 4 days/wk for 3 weeks. At the end of the experiment, we performed lung function parameters (respiratory rate, tidal volume, airflow rate), inflammatory cytokines (interleukin [IL]-4, IL-5, IL-13), total and differential leukocytes in blood as well as bronchoalveolar lavage fluid (BALf) and histological examinations. The computational study indicated that TLR4 antagonist activity of soya PC is due to linoleic acid (18:2) fatty acid chain. Soya PC significantly suppressed the LPS-induced neutrophil adhesion in a concentration-dependent manner to 1 μg/mL. The treatment of soya PC (5 and 10 mg/kg, 18 days, i.p.) significantly improved the lung function parameters, total and differential leukocyte counts in blood and BALf in asthmatic rats. This efficacy of soya PC was in extent similar to dexamethasone (2.5 mg/kg, 18 days, i.p.). However, soya PC was superior to dexamethasone in terms of benefits. The protective action of soya PC may be due to TLR4 antagonist activity and linoleic acid composition.

The effect of corticosteroid therapy is still controversial on prevention of mortality in coronavirus disease‐2019 (COVID‐19). The objective of this study is to investigate the effect of corticosteroids on mortality. This systematic review was performed as per preferred reporting items for systematic reviews and meta‐analyses guidelines. A systematic search was performed at different databases namely Medline/PubMed, Cochrane and Google scholar on 10 February 2022. A pooled estimate for effect of corticosteroid therapy on mortality was calculated as outcome of study. Risk bias analysis and Newcastle Ottawa Scale were used to assess the quality of randomized control trial (RCT) and cohort studies, respectively. Cochran's Q test and the I2 statistic were conducted for heterogeneity and accordingly study model was applied. A total 43 studies were included, having sample size of 96,852 patients. Amongst them, 19,426 and 77,426 patients received corticosteroid therapy (intervention group) or standard treatment without corticosteroid (control group), respectively. Mortality observed in the intervention and control group was 14.2% (2749) and 7.1% (5459), respectively. The pooled estimate 2.173 (95% CI: 2.0690–2.2820) showed significantly increased mortality in intervention as compared to control. The pooled estimate of methyprednisolone 1.206 (95% CI: 1.0770–1.3500) showed significantly increased mortality while the pooled estimate of dexamethasone 1.040 (95% CI: 0.9459–1.1440) showed insignificantly increased mortality as compared to control. In conclusion, corticosteroid therapy produced a negative prognosis as depicted by increased mortality among COVID‐19 patients. The possible reasons might be delay in virus clearance and secondary infections due to corticosteroids initiated at high dose in the early stage of infection.

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Retinal neurodegeneration is considered an early event in the pathogenesis of several ocular diseases, such as diabetic retinopathy, age-related macular degeneration, and glaucoma. At present, there is no definitive treatment to prevent the progression or reversal of vision loss caused by photoreceptor degeneration and the death of retinal ganglion cells. Neuroprotective approaches are being developed to increase the life expectancy of neurons by maintaining their shape/function and thus prevent the loss of vision and blindness. A successful neuroprotective approach could prolong patients’ vision functioning and quality of life. Conventional pharmaceutical technologies have been investigated for delivering ocular medications; however, the distinctive structural characteristics of the eye and the physiological ocular barriers restrict the efficient delivery of drugs. Recent developments in bio-adhesive in situ gelling systems and nanotechnology-based targeted/sustained drug delivery systems are receiving a lot of attention. This review summarizes the putative mechanism, pharmacokinetics, and mode of administration of neuroprotective drugs used to treat ocular disorders. Additionally, this review focuses on cutting-edge nanocarriers that demonstrated promising results in treating ocular neurodegenerative diseases.

An over activation of GPCR mediated Gαq dependent signalling pathway is widely associated with the development of cardiovascular abnormalities. The objective of study was to evaluate the effects of (1‐(5‐chloro‐2‐hydroxyphenyl)‐3‐(4‐(trifluoromethyl)phenyl)‐1H‐1,2,4‐triazol‐5(4H)‐one) Gαq‐RGS2 signalling inhibitor on aminophylline induced cardiac arrhythmia in rats. Rats were divided into four groups; normal rats, disease control (DC, aminophylline treated 100 mg/kg/d, i.p., 7 days), Gαq‐RGS2 signalling inhibitor (1 and 10 mg/kg/d, p.o., 7 days) treated arrhythmic rats. Gαq‐RGS2 signalling inhibitor was administered 1 hour prior to the administration of aminophylline from 1st day. At the end of study, heart rate (HR), QRS complex, QT and RR interval were measured by electrocardiogram (ECG) of anesthetized rats. Systolic and diastolic blood pressure (SBP, DBP) by invasive method, cardiac damage markers (CK‐MB, LDH) in the serum, antioxidant enzymes (SOD, catalase, glutathione) and cAMP level were measured. The treatment of Gαq‐RGS2 signalling inhibitor (10 mg/kg) significantly abolished the aminophylline induced increase of heart rate, prolongation of RR and QT interval as compared to DC rats. Gαq‐RGS2 signalling inhibitor (1 and 10 mg/kg) significantly attenuated the prolongation in QRS complex, increase of SBP, DBP and cardiac damage markers as compared to DC. Gαq‐RGS2 signalling inhibitor treatment (10 mg/kg) significantly reduced the cAMP level and increased the antioxidant enzyme level as compared to DC. Gαq‐RGS2 signalling inhibitor (10 mg/kg) showed the protective effect against the aminophylline induced cardiac arrhythmia and it might be due to improvement in cAMP level and antioxidant enzymes.

Background and Purpose: Corticosteroid therapy is still controversial to use for treatment of coronavirus disease-2019 (COVID-19). The results of multiple randomized clinical trials (RCTs) and observational studies are very diverse and contradictory, which arising difficulty in the clinical decision-making. The objective of this study is to investigate the effect of corticosteroids on mortality by systematic review and meta-analysis. External Approach: A systematic search was performed on different databases namely Medline/PubMed, Cochrane and Google scholar on 10 February 2022, according to PRISMA guidelines. The 28-days mortality was considered as outcome of study. A pooled estimate was calculated with random effects and fixed effects models. Cochran’s Q test and the I2 statistic were conducted for statistical heterogeneity. Key Results: 38 studies were included, having sample size of 87,781 patients. Amongst them, 16437 patients received corticosteroid therapy (intervention group) while 71344 patients were standard (noncorticosteroids) therapy (control group). 12.68% (2084) mortality observed in the intervention group while 5.93% (4227) mortality observed in the control group. The overall pooled estimate showed a significantly (OR2.305;95%CI: 2.1810 to 2.4370) increased mortality in intervention group. A pooled fold change estimation showed significantly increased in the mortality in methylprednisolone (OR 1.206;95%CI: 1.0770 to 1.3500) and dexamethasone (OR 1.388;95% CI:1.1870 to 1.6220) therapy. Conclusion and Implication: In conclusion, corticosteroid therapy produced a negative prognosis as depicted by increased mortality among COVID-19 patients. The possible reasons might be delay in virus clearance and secondary infection due to initiation of the corticosteroids at high dose in the early stage of infection.