scholarly journals CRISPR-Cas System: The Powerful Modulator of Accessory Genomes in Prokaryotes

2021 ◽  
pp. 1-16
Author(s):  
Anca Butiuc-Keul ◽  
Anca Farkas ◽  
Rahela Carpa ◽  
Dumitrana Iordache

Being frequently exposed to foreign nucleic acids, bacteria and archaea have developed an ingenious adaptive defense system, called CRISPR-Cas. The system is composed of the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) array, together with CRISPR (<i>cas</i>)-associated genes. This system consists of a complex machinery that integrates fragments of foreign nucleic acids from viruses and mobile genetic elements (MGEs), into CRISPR arrays. The inserted segments (spacers) are transcribed and then used by cas proteins as guide RNAs for recognition and inactivation of the targets. Different types and families of CRISPR-Cas systems consist of distinct adaptation and effector modules with evolutionary trajectories, partially independent. The origin of the effector modules and the mechanism of spacer integration/deletion is far less clear. A review of the most recent data regarding the structure, ecology, and evolution of CRISPR-Cas systems and their role in the modulation of accessory genomes in prokaryotes is proposed in this article. The CRISPR-Cas system&apos;s impact on the physiology and ecology of prokaryotes, modulation of horizontal gene transfer events, is also discussed here. This system gained popularity after it was proposed as a tool for plant and animal embryo editing, in cancer therapy, as antimicrobial against pathogenic bacteria, and even for combating the novel coronavirus – SARS-CoV-2; thus, the newest and promising applications are reviewed as well.

2021 ◽  
Vol 22 (1) ◽  
pp. 91-107
Author(s):  
F. S. Lobato ◽  
G. M. Platt ◽  
G. B. Libotte ◽  
A. J. Silva Neto

Different types of mathematical models have been used to predict the dynamic behavior of the novel coronavirus (COVID-19). Many of them involve the formulation and solution of inverse problems. This kind of problem is generally carried out by considering the model, the vector of design variables, and system parameters as deterministic values. In this contribution, a methodology based on a double loop iteration process and devoted to evaluate the influence of uncertainties on inverse problem is evaluated. The inner optimization loop is used to find the solution associated with the highest probability value, and the outer loop is the regular optimization loop used to determine the vector of design variables. For this task, we use an inverse reliability approach and Differential Evolution algorithm. For illustration purposes, the proposed methodology is applied to estimate the parameters of SIRD (Susceptible-Infectious-Recovery-Dead) model associated with dynamic behavior of COVID-19 pandemic considering real data from China's epidemic and uncertainties in the basic reproduction number (R0). The obtained results demonstrate, as expected, that the increase of reliability implies the increase of the objective function value.


2018 ◽  
Vol 6 (3) ◽  
pp. 438-451 ◽  
Author(s):  
Yuwei Zhu ◽  
Zhiwei Huang

Abstract Clustered regularly interspaced short palindromic repeats (CRISPR) and accompanying CRISPR-associated (Cas) proteins provide RNA-guided adaptive immunity for prokaryotes to defend themselves against viruses. The CRISPR-Cas systems have attracted much attention in recent years for their power in aiding the development of genome editing tools. Based on the composition of the CRISPR RNA-effector complex, the CRISPR-Cas systems can be divided into two classes and six types. In this review, we summarize recent advances in the structural biology of the CRISPR-Cas-mediated genome editing tools, which helps us to understand the mechanism of how the guide RNAs assemble with diverse Cas proteins to cleave target nucleic acids.


2021 ◽  
Vol 8 ◽  
Author(s):  
Setare Kheyrandish ◽  
Amirhossein Rastgar ◽  
Morteza Arab-Zozani ◽  
Gholamreza Anani Sarab

Background and Objective: Infection by the novel coronavirus disease 2019 (COVID-19) has been associated with different types of thrombotic complications same as portal vein thrombosis (PVT). However, by emerging vaccines of COVID, the thrombosis did not seem to be concerning anymore. Until new findings showed that, the vaccine of COVID itself can cause PVT.Method: We performed an electronic search in PubMed, Scopus, and Web of Sciences to evaluate the possibility of occurring PVT due to infection and vaccination of COVID-19. The results were reported in a narrative method and categorized into tables.Result: Overall, 40 cases of PVT from 34 studies were reviewed in this article. The prevalence of PVT following COVID-19 was more remarkable in males. However, it was more common in females after vaccinations of COVID-19 in the reviewed cases. Regardless of etiology, 20 of PVT cases reviewed in this article had at least one comorbidity. The most common clinical presentation was abdominal pain (AP). After anticoagulant therapies, most of the patients improved or discharged.Conclusion: As long as the laboratory findings are not appropriate enough to predict PVT, the diagnosis of this complication with whatever underlying reason is challengeable, while rapid diagnosis and treatment of that are vital. Therefore, by providing available data in an organized way, we aimed to prepare the information of infected patients for better and easier future diagnosis of PVT in new cases.


2021 ◽  
Vol 18 (6) ◽  
pp. 8683-8726
Author(s):  
Sumati Kumari Panda ◽  
◽  
Abdon Atangana ◽  
Juan J. Nieto ◽  
◽  
...  

<abstract><p>Extended orthogonal spaces are introduced and proved pertinent fixed point results. Thereafter, we present an analysis of the existence and unique solutions of the novel coronavirus 2019-nCoV/SARS-CoV-2 model via fractional derivatives. To strengthen our paper, we apply an efficient numerical scheme to solve the coronavirus 2019-nCoV/SARS-CoV-2 model with different types of differential operators.</p></abstract>


2020 ◽  
Vol 7 (3) ◽  
pp. 309-324
Author(s):  
Susana Del Toro-Arreola ◽  
Fabiola Solorzano-Ibarra ◽  
Martha C. Téllez-Bañuelos ◽  
Jesse Haramati

The outbreak of the novel coronavirus SARS-CoV-2 and the attendant physiological symptoms associated with the COVID-19 disease have led to an explosion of interest studying different aspects of the immune response. As of yet, the particular roles of natural killer cells are not well understood in this disease. NK cells are critical first-response cytotoxic cells of the innate immune system. NK cells are traditionally considered important for their roles in innate immunity against tumors and viral infected cells, as well as their ability to produce cytokines, particularly interferon-?, and participate in antibody dependent cell cytotoxicity (ADCC). Here, we describe the role of NK cells in peripheral blood and in the lungs with respect to the pathology caused by SARS-CoV-2 and discuss the implications of proposed different types of therapies on NK cells. Evidence is accumulating that NK cells play an important role in initial surveillance as part of innate immunity. With the progression of the disease and rising inflammation, these cells, when in circulation, appear to become exhausted and ineffective. In the COVID lung, however, a complex interplay between inflammatory cells, chemokines, cytokines and aberrantly activated migratory NK cells occurs, potentiating local inflammation and the critical situation in the lungs.


Author(s):  
Jan Fuhrmann ◽  
Maria Vittoria Barbarossa

In attempting to predict the further course of the novel coronavirus (COVID-19) pandemic caused by SARS-CoV-2, mathematical models of different types are frequently employed and calibrated to reported case numbers. Among the major challenges in interpreting these data is the uncertainty about the amount of undetected infections, or conversely: the detection ratio. As a result, some models include assumptions about the percentage of detected cases among total infections while others completely neglect undetected cases. Here, we illustrate how model projections about case and fatality numbers vary significantly under varying assumptions on the detection ratio. Uncertainties in model predictions can be significantly reduced by representative testing, both for antibodies and active virus RNA, to uncover past and current infections that have gone undetected thus far.


2011 ◽  
Vol 392 (4) ◽  
Author(s):  
Sinan Al-Attar ◽  
Edze R. Westra ◽  
John van der Oost ◽  
Stan J.J. Brouns

AbstractMany prokaryotes contain the recently discovered defense system against mobile genetic elements. This defense system contains a unique type of repetitive DNA stretches, termed Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs). CRISPRs consist of identical repeated DNA sequences (repeats), interspaced by highly variable sequences referred to as spacers. The spacers originate from either phages or plasmids and comprise the prokaryotes' ‘immunological memory’. CRISPR-associated (cas) genes encode conserved proteins that together with CRISPRs make-up the CRISPR/Cas system, responsible for defending the prokaryotic cell against invaders. CRISPR-mediated resistance has been proposed to involve three stages: (i) CRISPR-Adaptation, the invader DNA is encountered by the CRISPR/Cas machinery and an invader-derived short DNA fragment is incorporated in the CRISPR array. (ii) CRISPR-Expression, the CRISPR array is transcribed and the transcript is processed by Cas proteins. (iii) CRISPR-Interference, the invaders' nucleic acid is recognized by complementarity to the crRNA and neutralized. An application of the CRISPR/Cas system is the immunization of industry-relevant prokaryotes (or eukaryotes) against mobile-genetic invasion. In addition, the high variability of the CRISPR spacer content can be exploited for phylogenetic and evolutionary studies. Despite impressive progress during the last couple of years, the elucidation of several fundamental details will be a major challenge in future research.


2018 ◽  
Author(s):  
Craig Westover ◽  
Savlatjon Rahmatulloev ◽  
David Danko ◽  
Ebrahim Afshinnekoo ◽  
Niamh B. O’Hara ◽  
...  

AbstractPathogenic bacteria and viruses in medical environments can lead to treatment complications and hospital-acquired infections (HAIs), and current cleaning protocols do not address hard-to-access areas or that may be beyond line-of-sight treatment such as with ultraviolet radiation. At the time of writing, the ongoing pandemic of the novel coronavirus known as novel coronavirus (2019-nCoV) has claimed over 4 million cases worldwide and is expected to have multiple peaks, with possible resurgences throughout 2020. It is therefore imperative that disinfection methods in the meantime be employed to keep up with the supply of personal protective equipment (PPE) and sterilize a wide array of surfaces as quarantine lockdowns begin to be lifted.Here, we tested the efficacy of Sani Sport ozone devices as a means to treat hospital equipment and surfaces for killing bacteria, degrading synthetic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA, and RNA from non-replicative capsid enclosed SARS-CoV-2. We observed a rapid killing of medically-relevant and environmental bacteria (Escherichia coli, Enterococcus faecalis, Bacillus subtlis, and Deinococcus radiodurans) across four surfaces (blankets, catheter, remotes, and syringes) within 30 minutes, and up to a 99% reduction in viable bacteria at the end of 2-hour treatment cycles. Significant RNA degradation of synthetic SARS-CoV-2 RNA was seen an hour into the ozone treatment as compared to non-treated controls and a non-replicative form of the virus was shown to have significant RNA degradation at 30 minutes compared to a no treatment control and RNA degradation could be reliably detected at 10,000 and 1,000 copies of virus per sample. These results show the strong promise of ozone treatment for reducing risk of infection and HAIs.


2020 ◽  
Author(s):  
Micael Davi Lima de Oliveira ◽  
Kelson Mota Teixeira de Oliveira

According to the World Health Organisation, until 16 June, 2020, the number of confirmed and notified cases of COVID-19 has already exceeded 7.9 million with approximately 434 thousand deaths worldwide. This research aimed to find repurposing antagonists, that may inhibit the activity of the main protease (Mpro) of the SARS-CoV-2 virus, as well as partially modulate the ACE2 receptors largely found in lung cells, and reduce viral replication by inhibiting Nsp12 RNA polymerase. Docking molecular simulations were performed among a total of 60 structures, most of all, published in the literature against the novel coronavirus. The theoretical results indicated that, in comparative terms, paritaprevir, ivermectin, ledipasvir, and simeprevir, are among the most theoretical promising drugs in remission of symptoms from the disease. Furthermore, also corroborate indinavir to the high modulation in viral receptors. The second group of promising drugs includes remdesivir and azithromycin. The repurposing drugs HCQ and chloroquine were not effective in comparative terms to other drugs, as monotherapies, against SARS-CoV-2 infection.


2020 ◽  
Vol 11 (SPL1) ◽  
pp. 977-982
Author(s):  
Mohamed J. Saadh ◽  
Bashar Haj Rashid M ◽  
Roa’a Matar ◽  
Sajeda Riyad Aldibs ◽  
Hala Sbaih ◽  
...  

SARS-COV2 virus causes Coronavirus disease (COVID-19) and represents the causative agent of a potentially fatal disease that is of great global public health concern. The novel coronavirus (2019) was discovered in 2019 in Wuhan, the market of the wet animal, China with viral pneumonia cases and is life-threatening. Today, WHO announces COVID-19 outbreak as a pandemic. COVID-19 is likely to be zoonotic. It is transmitted from bats as intermediary animals to human. Also, the virus is transmitted from human to human who is in close contact with others. The computerized tomographic chest scan is usually abnormal even in those with no symptoms or mild disease. Treatment is nearly supportive; the role of antiviral agents is yet to be established. The SARS-COV2 virus spreads faster than its two ancestors, the SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), but has lower fatality. In this article, we aimed to summarize the transmission, symptoms, pathogenesis, diagnosis, treatment, and vaccine to control the spread of this fatal disease.


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