Sirna-A Potential Therapy for Covid-19 Infection

Background: The deadly virus COVID-19 has affected more than 1 crore people and claimed more than 5 lakh lives worldwide according to the World health organization. Though there are numerous treatment modalities available including anti-bacterials, antivirals, vaccines etc., none of them can be considered as effective cure for SARS CoV-2 virus as they are mostly non-specific in action. Aim(s): siRNA therapy can be considered as a significant treatment modality due to its specificity in action. The aim of this review is to explore siRNA as a potential treatment strategy for the treatment of COVID-19. Material(s) and Method(s): In this review we shall explore the targets of siRNA therapy which includes viral RNA-dependent RNA polymerase, helicase, protease and nucleoprotein N. siRNA related patents provide solutions for novel RNAi techniques, high expense of chemically synthetic siRNA, techniques for restraining SARS-CoV by disturbing RNA etc., siRNA-based drug delivery systems and limitations of nanocarrier delivery system were reviewed. siRNA is a gene silencer that targets highly conserved sequences which codes for protease 3CL (nsp5) and viral helicase (from 16-18 kbp). Conclusion(s): Thus, siRNA-based therapy is considered highly efficacious as it can hit the highly conserved regions of SARS-CoV-2 RNA.Copyright © 2023, Advanced Scientific Research. All rights reserved.

Cyanovirin-N binds to select SARS-CoV-2 spike oligosaccharides outside of the receptor binding domain and blocks infection by SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped positive stranded RNA virus which has caused the recent deadly pandemic called COVID-19. The SARS-CoV-2 virion is coated with a heavily glycosylated Spike glycoprotein which is responsible for attachment and entry into target cells. One, as yet unexploited strategy for preventing SARS-CoV-2 infections, is the targeting of the glycans on Spike. Lectins are carbohydrate-binding proteins produced by plants, algae, and cyanobacteria. Some lectins can neutralize enveloped viruses displaying external glycoproteins, offering an alternative therapeutic approach for the prevention of infection with virulent ß-coronaviruses, such as SARS-CoV-2. Here we show that the cyanobacterial lectin cyanovirin-N (CV-N) can selectively target SARS-CoV-2 Spike oligosaccharides and inhibit SARS-CoV-2 infection in vitro and in vivo. CV-N neutralizes Delta and Omicron variants in vitro better than earlier circulating viral variants. CV-N binds selectively to Spike with a Kd as low as 15 nM and a stoichiometry of 2 CV-N: 1 Spike but does not bind to the receptor binding domain (RBD). Further mapping of CV-N binding sites on Spike shows that select high-mannose oligosaccharides in the S1 domain of Spike are targeted by CV-N. CV-N also reduced viral loads in the nares and lungs in vivo to protect hamsters against a lethal viral challenge. In summary, we present an anti-coronavirus agent that works by an unexploited mechanism and prevents infection by a broad range of SARS-CoV-2 strains.

Role of Hematological and Immunological Parameters in COVID-19 Patients.

BACKGROUND: The ongoing pandemic of coronavirus disease 2019 (COVID-19) which was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to efforts from the medical and scientific community in understanding the biological basis of COVID-19 pathophysiological mechanisms. Thus, analysis of various hematological and immunological parameters may be helpful for COVID-19 infection evaluation for risks involved and effectiveness in management. AIM: The aim of this study was to analyze the role of various hematological and immunological parameters in patients infected with SARS-CoV-2. MATERIALS AND METHODS: This retrospective analysis was performed on 300 patients who tested positive for SARS-CoV-2 by quantitative reverse transcription-polymerase chain reaction analysis. All participants of the study were divided into - (a) Group I: patients with mild symptoms and normal chest radiographic findings; (b) patients with moderate disease presenting with fever and cough along with other respiratory symptoms, and (c) patients suffering from severe disease. Data collection was done from all patients at the time of hospital admission for hematological and immunological parameters - (a) total leukocyte count, (b) lymphocyte count, (c) lymphocytic subset count, (d) lactate dehydrogenase (LDH) levels, (e) D-dimer, (f) C-reactive protein (CRP), and (g) ferritin levels. SPSS 22.0 software was used for determining P values by independent t-test and Chi-square test. RESULTS: The median age was 65 years (interquartile range -57-71 years). While comparing white blood cell and lymphocyte counts, extremely significant P values were obtained. D-dimers and ferritin levels demonstrated extremely significant P values while both LDH and CRPs showed statistical significance. Correlation of lymphocytic subsets showed extreme significance in total lymphocyte counts in mild-to-moderate as compared to severely infected patients while both CD4+ and CD8+ counts demonstrated statistical significance in mild-moderate infected cases. Statistical significance was noted in D-dimer, CRP, and LDH levels also. CONCLUSION: Assessment of hematological and immunological parameters can be used to plan the management of COVID-19 patients.

Coronavirus: A potential threat for dental practitioners

Coronaviruses are large, enveloped RNA viruses composed of few structural proteins and mainly infect birds and mammals including humans. The first case of coronavirus was described in China in December 2019. Novel coronavirus (SARS-CoV-2) infects the human respiratory, nervous, enteric, and hepatic systems. Individuals with a potential SARS-CoV-2 exposure present with the mild symptoms of low-grade fever, dry cough, shortness of breath, nasal congestion, and headache and muscle pain. In the later stages, these symptoms worsen leading to severe pneumonia, acute respiratory distress syndrome, sepsis, and multiple organ failure. These days this pandemic is emerging as a major threat for the health-care professionals including dental surgeons. The dental surgeons are at greater risk of novel coronavirus infections due to direct contact with infected patients and exposure to contaminated blood, saliva, and other body fluids. This article deals with viral structure, methods of detection, and modes of transmission, especially in dental settings. © 2020 Medknow.

Modifying nutritional substrates induces macrovesicular lipid droplet accumulation and metabolic alterations in a cellular model of hepatic steatosis

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) begins with steatosis, where a mixed macrovesicular pattern of large and small lipid droplets (LDs) develops. Since in vitro models recapitulating this are limited, the aims of this study were to develop mixed macrovesicular steatosis in immortalized hepatocytes and investigate effects on intracellular metabolism by altering nutritional substrates. METHODS: Huh7 cells were cultured in 11 mM glucose and 2% human serum (HS) for 7 days before additional sugars and fatty acids (FAs), either with 200 µM FAs (low fat low sugar;LFLS), 5.5 mM fructose + 200 µM FAs (low fat high sugar;LFHS), or 5.5 mM fructose + 800 µM FAs (high fat high sugar;HFHS), were added for 7 days. FA metabolism, lipid droplet characteristics, and transcriptomic signatures were investigated. RESULTS: Between the LFLS and LFHS conditions, there were few notable differences. In the HFHS condition, intracellular triacylglycerol (TAG) was increased and the LD pattern and distribution was similar to that found in primary steatotic hepatocytes. HFHS-treated cells had lower levels of de novo-derived FAs and secreted larger, TAG-rich lipoprotein particles. RNA sequencing and gene set enrichment analysis showed changes in several pathways including those involved in metabolism and cell cycle. CONCLUSIONS: Repeated doses of HFHS treatment resulted in a cellular model of NAFLD with a mixed macrovesicular LD pattern and metabolic dysfunction. Since these nutrients have been implicated in the development of NAFLD in humans, the model provides a good physiological basis for studying NAFLD development or regression in vitro.