Nuclear entry of poliovirus protease-polymerase precursor 3CD: implications for host cell transcription shut-off

AbstractHost cell transcription mediated by all three RNA polymerases is rapidly inhibited after infection of mammalian cells with poliovirus (PV). Both genetic and biochemical studies have shown that the virus-encoded protease 3C cleaves the TATA-binding protein and other transcription factors at glutamine–glycine sites and is directly responsible for host cell transcription shut-off. PV replicates in the cytoplasm of infected cells. To shut-off host cell transcription, 3C or a precursor of 3C must enter the nucleus of infected cells. Although the 3C protease itself lacks a nuclear localization signal (NLS), amino acid sequence examination of 3D identified a potential single basic type NLS, KKKRD, spanning amino acids 125–129 within this polypeptide. Thus, a plausible scenario is that 3C enters the nucleus in the form of its precursor, 3CD, which then generates 3C by auto-proteolysis ultimately leading to cleavage of transcription factors in the nucleus. Using transient transfection of enhanced green fluorescent protein (EGFP) fusion polypeptides, we demonstrate here that both 3CD and 3D are capable of entering the nucleus in PV-infected cells. However, both polypeptides remain in the cytoplasm in uninfected HeLa cells. Mutagenesis of the NLS sequence in 3D prevents nuclear entry of 3D and 3CD in PV-infected cells. We also demonstrate that 3CD can be detected in the nuclear fraction from PV-infected HeLa cells as early as 2 h postinfection. Significant amount of 3CD is found associated with the nuclear fraction by 3–4 h of infection. Taken together, these results suggest that both the 3D NLS and PV infection are required for the entry of 3CD into the nucleus and that this may constitute a means by which viral protease 3C is delivered into the nucleus leading to host cell transcription shut-off

Reconsidering Traditional Medicinal Plants to Combat COVID-19

COVID – 19 is a deadly disease, caused by a novel coronavirus (SARS-CoV-2) that is rapidly spreading across the globe and causing many fatalities. WHO (World Health Organization) has declared this disease as pandemic. Currently the disease has no treatment available in the form of medicine or vaccine. Ayurveda is an ancient Indian system of medicine, been practiced in India for nearly 5000 years and relies majorly on plants for its formulations. These herbal formulations and immunity boosters may show us the path to come up with a broad-spectrum antiviral product, which is the need of the hour. In this review, we have selected plants like Phyllanthus spp., Andrographis paniculata, Curcuma longa, Zingiber officinale, Glycyrrhiza glabra, and Withania somnifera with reported antiviral properties. While others like Tinospora cordifolia and Emblica officinalis that have immunity boosting properties.  The exact mechanisms of action for all the plants may not be clear as per modern medicine, but their history of safe use is in place

Therapeutic and Nutritional Potential of Spirulina in Combating COVID-19 Infection

Human history has witnessed various pandemics throughout, and these cause disastrous effects on human health and country’s economy. Once again, after SARS (Severe Acute Respiratory Syndrome) and MERS (Middle East Respiratory Syndrome), the world is observing a very tough time fighting an invisible enemy, the novel COVID-19 coronavirus. Initially observed in the Wuhan province of China, now, it has spread across 210 countries. Number of corona affected confirmed cases have reached > 3 million globally and death toll has reached to 258,481 as on 6th May,2020. Researchers are working round the clock, forming collaborative efforts and sharing their data to come up with a cure for this disease. The new coronavirus genome was quickly sequenced and clinical and epidemiological data are continuously being collected and analyzed. This data is crucial for forming better public health policies and developing antiviral drugs and vaccines. As there is no vaccine available in market against COVID-19, personal health, immunity, social distancing and basic protection measures are extremely important. It is critical to avoid the virus infection and to strengthen the immune system as the coronavirus can be fatal for those with weak immunity.  This article reviews the nutritional and therapeutic potential of Spirulina, which is considered as superfood and a natural supplement to strengthen the immune system. Spirulina is highly nutritious and has hypolipidemic, hypoglycemic and antihypertensive properties. Spirulina contains several bioactive compounds, such as phenols, phycobiliproteins and sulphated polysaccharides and many more with proven antioxidant, anti-inflammatory and immunostimulant/ immunomodulatory effects

Use of Bacterial Acetate Kinase and Their Genes for Protection of Plants Against Different Pathogens

An isolated gene fragment that encodes for acetate kinase, which confers disease resistance in plants is disclosed. The gene can be cloned into an expression vector to produce a recombinant DNA expression system suitable for insertion into cells to form a transgenic plant transformed with the gene fragment. A method for conferring disease resistance in plants that consists of growing plant host cells transformed with the expression system and expressing the gene conferring disease resistance to impart such resistance to host cells is also disclosed

Possible Prevention of COVID 19 by Using Linoleic Acid (C18) Rich Algae Oil

With the rapid spread of COVID 19, people are being isolated in countries, and more than lakhs of people have been infecting by the coronavirus. The coronavirus is an airborne organism and highly infectious at short contact distances. The use of N95 respirators masks (high-efficiency) can protect people against the COVID 19, but the protective efficiency of masks is not high enough. A method of applying oil with rich amounts of linoleic acid in nostrils can prevent the spread of the virus. Macroalgal secondary metabolites have great potential for the development of new drugs and algae derived products largely employed in assorted industries, including agricultural, biomedical, food, and pharmaceutical industries. Among different chemical components isolated from algae, oil components are the most attracting more and which were subjected to a variety of studies (antiviral potential of algae in pharmaceutical research). Algal oil and their components like linoleic acid, oleic acid, palmitic acid, stearic acid are playing a preventive role in the virus infection. In addition, different mechanisms of action have been reported for these linoleic acid (C18H32O2) components, such as inhibiting the binding virus into the host cells or suppressing virulence activity by destabilization of the bilayer of viral envelopes. Application of in controlling the virus entry is mainly depend on the properties like low surface tension, high-boiling point, high viscosity, immiscible with water and antivirus activity. This manuscript mainly discusses the possible physical-chemical mechanisms involved in the application of algal oil and other sources of oils component's role in prevention of viral spread. Among that we listed out various oil sources and their applications in controlling the virus activity. Further confirmed experimental and clinical results for the use of oils as nasal spray may finally contribute to preventing the spread of the coronavirus as soon as possible

Marine Algae as a Natural Source for Antiviral Compounds

Coronavirus or COVID-19 is started from the China, Wuhan city in December 2019 and soon later, spread around 190 countries and declared as pandemic on March 11, 2020 by WHO. Healthcare systems all over the world are fighting against this pandemic. Most of the countries are lockdown for uncertain periods to protect their people from this pandemic as a result the world economy is struggling to cope up with the current situation. Several countries have conducted research studies to produce vaccine or antiviral drug but there is still no specific solution for the prevention or treatment of COVID-19 infection in general. Along with other treatment methods, many countries are fuelling their demand for antiviral compounds from natural resources due to coronavirus. Microalgae and cyanobacteria are excellent source of antiviral activity. Several cyclic or linear peptides and depsipeptides isolated from cyanobacteria are protease inhibitors, which is considered as significant antiviral candidate. Micro and macroalgae were one of the first sources of natural compounds showing in vitro anti-HIV activity. Numerous in vitro or in vivo studies has shown the potential of algae against wild range of viruses. The use of natural products in the manufacturing of drugs is an ancient and well-established practice. Marine microorganisms are known producers of pharmacological and anti-viral agents and may provide unlimited biological resources to produce therapeutic drugs for the treatment and control of viral diseases in humans. Our major intention to write this review to bring world’s attention in terms of public health and public policy practices across the world to grab an opportunity from this known healthcare practices, and conventional platform to produce vaccine or antiviral medicine to overcome COID-19

Intracellular locations of replication proteins and the origin of replication during chromosome duplication in the slowly growing human pathogen Helicobacter pylori

We followed the position of the replication complex in the pathogenic bacterium Helicobacter pylori using antibodies raised against the single-stranded DNA binding protein (HpSSB) and the replicative helicase (HpDnaB). The position of the replication origin, oriC, was also localized in growing cells by fluorescence in situ hybridization (FISH) with fluorescence-labeled DNA sequences adjacent to the origin. The replisome assembled at oriC near one of the cell poles and the two forks moved together toward the cell center as replication progressed in the growing cell. Termination and resolution of the forks occurred near midcell, on one side of the septal membrane. The duplicated copies of oriC did not separate until late in elongation, when the daughter chromosomes segregated into bilobed nucleoids, suggesting sister chromatid cohesion at or near the oriC region. Components of the replication machinery, viz., HpDnaB and HpDnaG (DNA primase), were found associated with the cell membrane. A model for the assembly and location of the H. pylori replication machinery during chromosomal duplication is presented

Racial Disparities in the Genetic Landscape of Lung Cancer

Lung cancer has the highest cancer-related mortality worldwide and in the United States. Reduced tobacco consumption and advancement in therapies have led to a modest decline in lung cancer death rates over the past two decades; the overall survival rate is still disappointing.  Moreover, race-associated disparities are also observed, especially in the clinical outcomes. While differences in socioeconomic status and lifestyle could be significant contributing factors, differences in the genetic landscape of lung cancer among different racial groups have also been reported.  In this review, we shed light on the genetic heterogeneity of lung cancer and race-associated differences in genetic alterations to build a framework for future studies to understand the biological basis of lung cancer disparities

Role of the ribosome in protein folding

In all organisms, the ribosome synthesizes and folds full length polypeptide chains into active three-dimensional conformations. The nascent protein goes through two major interactions, first with the ribosome which synthesizes the polypeptide chain and holds it for a considerable length of time, and then with the chaperones. Some of the chaperones are found in solution as well as associated to the ribosome. A number of in vitro and in vivo experiments revealed that the nascent protein folds through specific interactions of some amino acids with the nucleotides in the peptidyl transferase center (PTC) in the large ribosomal subunit. The mechanism of this folding differs from self-folding. In this article, we highlight the folding of nascent proteins on the ribosome and the influence of chaperones etc. on protein folding