The effects of killer cell immunoglobulin-like receptor (KIR) genes on susceptibility to severe COVID-19 in the Iranian population.

BACKGROUND: Variations in the innate and adaptive immune response systems are linked to variations in the severity of COVID-19. Natural killer cell (NK) function is regulated by sophisticated receptor system including Killer-cell immunoglobulin-like receptor (KIR) family. We aimed to investigate the impact of possessing certain KIR genes and genotypes on COVID19 severity in Iranians. KIR genotyping was performed on 394 age/sex matched Iranians with no underlying conditions who developed mild and severe COVID- 19. The presence and/or absence of 11 KIR genes were determined using the PCR with sequence specific primers (PCR-SSP). RESULTS: Patients with mild symptoms had higher frequency ofKIR2DS1 (p = 0.004) and KIR2DS2 (p = 0.017) genes compared to those with severe disease. While KIR3DL3 and deleted variant of KIR2DS4 occurred more frequently in patients who developed a severe form of the disease. In this study, a significant increase of and B haplotype was observed in the Mild group compared to the Severe group (respectively, p = 0.002 and p = 0.02). Also, the prevalence of haplotype A was significantly higher in the Severe group than in the Mild group (p = 0.02). CONCLUSIONS: These results suggest that the KIR2DS1, KIR2DS, and B haplotype maybe have a protective effect against COVID-19 severity. The results also suggest the inhibitory gene KIR2DL3 and haplotype A are risk factors for the severity of COVID-19.

Targeting host calcium channels and viroporins: a promising strategy for SARS-CoV-2 therapy.

Despite passing the pandemic phase of the COVID-19, researchers are still investigating various drugs. Previous evidence suggests that blocking the calcium channels may be a suitable treatment option. Ca2+ is required to enhance the fusion process of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Also, some important inflammatory factors during SARS-CoV-2 infection are dependent on Ca2+ level. On the other hand, viroporins have emerged as attractive targets for antiviral therapy due to their essential role in viral replication and pathogenesis. By inhibiting the host calcium channels and viroporins, it is possible to limit the spread of infection. Therefore, calcium channel blockers (CCBs) and drugs targeting Viroporins can be considered an effective option in the fight against SARS-CoV-2.

The role of SARS-CoV-2 accessory proteins in immune evasion.

Many questions on the SARS-CoV-2 pathogenesis remain to answer. The SARS-CoV-2 genome encodes some accessory proteins that are essential for infection. Notably, accessory proteins of SARS-CoV-2 play significant roles in affecting immune escape and viral pathogenesis. Therefore SARS-CoV-2 accessory proteins could be considered putative drug targets. IFN-I and IFN-III responses are the primary mechanisms of innate antiviral immunity in infection clearance. Previous research has shown that SARS-CoV-2 suppresses IFN-ß by infecting host cells via ORF3a, ORF3b, ORF6, ORF7a, ORF7b, ORF8, and ORF9b. Furthermore, ORF3a, ORF7a, and ORF7b have a role in blocking IFNα signaling, and ORF8 represses IFNß signaling. The ORF3a, ORF7a, and ORF7b disrupt the STAT1/2 phosphorylation. ORF3a, ORF6, ORF7a, and ORF7b could prevent the ISRE promoter activity. The main SARS-CoV-2 accessory proteins involved in immune evasion are discussed here for comprehensive learning on viral entry, replication, and transmission in vaccines and antiviral development.

CRISPR-Cas System: A Promising Diagnostic Tool for Covid-19.

More than a year has passed since the beginning of the 2019 novel coronavirus diseases (COVID-19) pandemic which has created massive problems globally affecting all aspects of people's life. Due to the emergence of new strains of the SARS-CoV-2, pandemic risk still remains, despite the start of vaccination. Therefore, rapid diagnostic tests are essential to control infection, improve clinical care and stop the spread of the disease. Recently CRISPR-based diagnostic tools have facilitated rapid diagnostic. Here, we review the diagnostic applications of CRISPR-Cas system in COVID-19.

Target genes used for biosensor development in COVID-19 diagnosis.

In a published review entitled "COVID-19 diagnosis -A review of current methods", the authors considered hemagglutinin esterase as one of the structural proteins of SARS-CoV-2 and also they did not represent ORF3b, ORF9b, and ORF9c in SARS-CoV-2 genome structure. However, according to the scientific evidence, among coronaviruses only some betacoronaviruses (Embecovirus subgenera) contain HE, and the genome of most of the coronaviruses such as SARS-CoV-2, SARS-CoV, and MERS-CoV lack the HE gene. In addition, the genome of SARS-CoV-2 contains several accessory proteins ORFs including ORF3a, ORF3b, ORF6, ORF7a, ORF7b, ORF8, ORF9b, ORF9c, and ORF10.

Comparison between various biosensor methods for human T-lymphotropic virus-1 (HTLV-1) detection.

Due to the drawback of traditional and current diagnostic methods including serological and molecular assays, the development of the rapid and free-PCR techniques can be an alternative technique for the human T-cell lymphotropic virus (HTLV-1) DNA detection sequences. On the other hand, early detection of HTLV-1 prevents two dangerous diseases including Adult T-cell leukemia/lymphoma and HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis. The biosensor-based methods are sensitive techniques that can provide new opportunities to detect infectious diseases, particularly in the early stage. This study provides a comparative view among recently designed biosensors for the detection of HTLV-1.

Severe acute respiratory syndrome coronavirus 2 and respiratory syncytial virus coinfection in children.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has infected many people around the world. Children are considered an important target group for SARS-CoV-2, as well as other viral infections such as respiratory syncytial virus infection. Both SARS-CoV-2 and respiratory syncytial virus can affect the respiratory tract. Coinfection of SARS-CoV-2 and respiratory syncytial virus can pose significant challenges in terms of diagnosis and treatment in children. This review compares the symptoms, diagnostic methods, and treatment of COVID-19 and respiratory syncytial virus infection in children.

Rapid and label-free electrochemical DNA biosensor based on a facile one-step electrochemical synthesis of rGO-PPy-(L-Cys)-AuNPs nanocomposite for the HTLV-1 oligonucleotide detection.

Human T cell leukemia virus type 1 (HTLV-1) as the first human retrovirus is currently a serious endemic health challenge. Despite the use of assorted molecular or serological assays for HTLV-1 detection, there are several limitations due to the lack of a confirmatory test that may affect the accuracy of the results. Herein, a novel label-free biosensor for the detection of HTLV-1 Tax gene has been reported. An electrochemical facile ecofriendly synthesis method has been demonstrated based on a synthesis of nanocomposite of reduced graphene oxide, polypyrrole, and gold nanoparticles (rGO-PPy-(l-Cys)-AuNPs) deposited on the surface of screen-printed carbon electrode. Electrochemical techniques were used to characterize and study the electrochemical behavior of the rGO-PPy-(l-Cys)-AuNPs, which exhibited a stable reference peak at 0.21 V associated with hybridization forms by applying the differential pulse voltammetry. The designed DNA biosensor presented a wide linear range from 0.1 fM to 100 µM and a low detection limit of 20 atto-molar. The proposed biosensor presented in this study provides outstanding selectivity, sensitivity, repeatability, and reproducibility.

Future developments in biosensors for field-ready SARS-CoV-2 virus diagnostics.

According to the evidence, the coronavirus disease 19 (COVID-19) is caused by a zoonotic pathogen named respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus can spread through personal contact, respiratory droplets, and also through airborne transmission. A rapid, low-cost, and effective biosensor platform is essential to diagnose patients with COVID-19 infection, predominantly the asymptomatic individuals, and prevent the spread of the SARS-CoV-2 via transmission routes. The objective of this review is to provide a comparative view among current diagnostic methods, focusing on recently suggested biosensors for the detection of SARS-CoV2 in clinical samples. A capable SARS-CoV-2 biosensor can be designed by the holistic insights of various biosensor studies.

A knockdown of the herpes simplex virus type-1 gene in all-in-one CRISPR vectors.

INTRODUCTION: Herpes simplex virus type 1 (HSV-1) is a virus that causes serious human disease and establishes a long-term latent infection. The latent form of this virus has shown to be resistant to antiviral drugs. Clustered Regularly Interspace Short Palindromic Repeats (CRISPR), is an important tool in genome engineering and composed of guide RNA (gRNA) and Cas9 nuclease that makes an RNA-protein complex to digest exclusive target sequences implementation of gRNA. Moreover, CRISPR-Cas9 system effectively suppresses HSV-1 infection by knockout of some viral genes. MATERIALS AND METHODS: To survey the efficacy of Cas9 system on HSV-1 genome destruction, we designed several guide RNAs (gRNAs) that all packaged in one vector. Additionally, we performed a one-step restriction using BamHI and Esp3I enzymes. RESULTS: CRISPR/Cas9 system targeted against the gD gene of HSV-1 was transfected into HEK-AD cells that showed a significant reduction of HSV-1 infection by plaque assay and real-time PCR. CONCLUSION: The pCas-Guide-EF1a-GFP CRISPR vector can create a fast and efficient method for gRNA cloning by restriction enzymes (Esp3I (BsmBI) and BamHI). Therefore, the CRISPR/Cas9 system may be utilized for the screening of genes critical for the HSV-1 infection and developing new strategies for targeted therapy of viral infections caused by HSV-1.

Correlation of human papillomavirus 16 and 18 with cervical cancer and their diagnosis methods in Iranian women: A systematic review and meta-analysis.

BACKGROUND: Human papillomavirus (HPV) is a sexually transmitted virus and related to the development of cervical cancer (CC). To determine the association between high-risk HPV types and CC, we undertook a systematic review and meta-analysis of recently reported prevalence of HPV16 and 18 in Iranian women identified with cervical infections. MATERIALS AND METHODS: Prevalence studies were identified between 2002 and 2018 using several databases including Medline, Web of Science, Embase, Google Scholar, Iranmedex, and Scientific Information Database. RESULTS: For patients with CC, 57% (95% confidence interval [95% CI] = 43.7%-70.4%) were HPV positive, 48.5% (95% CI = 31.8%-65.2%) were HPV16 and 12.5% (95% CI = 8.8%-16.2%) were HPV18 positive. CONCLUSION: The results from meta-analysis indicate a relatively high prevalence of high-risk HPV among women infected with CC.

Zinc Sulfate in Narrow Range as an In Vitro Anti-HSV-1 Assay.

This report explains the employing of a combination test of traditional cell culture with a quantitative real-time PCR for assessment of the antiviral effect of zinc sulfate (ZnSO4) on herpes simplex virus (HSV)-infected Vero cells. Our evidence showed that the treatment with 0.3 mM ZnSO4 strongly inhibited the replication of virus progeny (MOI 0.001) at least 68-fold less. On the other hand, the IC50 demonstrated that the highest activity of ZnSO4 was at the 0.23 mM concentration.

Current approaches for detection of human T-lymphotropic virus Type 1: A systematic review.

BACKGROUND: Human T-lymphotropic virus Type 1 (HTLV-1) is a retrovirus that is endemic in some regions of the world. It is known to cause several diseases like adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Serology and molecular methods have been used to detect this virus. Of these, enzyme-linked immunosorbent assay (ELISA) is used as a primary screening method and this is usually followed by western blotting (WB) and polymerase chain reaction (PCR) methods as confirmatory tests. We conducted a systematic review of the different techniques used in the diagnosis of HTLV-1 infection. MATERIALS AND METHODS: Our search was limited to original papers in the English language from 2010 to 2018 using several databases including Pubmed, Scopus, Google Scholar, Iranmedex, and Scientific Information Database. A manual search of references provided in the included papers was also performed. RESULTS: Of 101 electronically searched citations, 43 met the inclusion criteria. ELISA is commonly used for qualitative and screening detection, and WB and PCR techniques are used to confirm infection. CONCLUSION: Among all the reported methods for detection of HTLV-1, only serological and molecular tests are used as the most common technical assays for HTLV-1. The ELISA assay, without a confirmatory test, has several limitations and affect the accuracy of the results. Owing to the prevalence of HTLV-1 and limitations of the current detection methods, further evaluation of the accuracy of these methods is needed. There are new opportunities for applying novel technological advances in microfluidics, biosensors, and lab-on-a-chip systems to perform HTLV-1 diagnostics.

Early detection of cervical cancer based on high-risk HPV DNA-based genosensors: A systematic review.

Human papillomavirus type (HPV) is a common cause of sexually transmitted disease (STD) in humans. HPV types 16 and 18 as the highest risk types are related with gynecologic malignancy and cervical cancer (CC) among women worldwide. Recently, considerable development of genosensors, which allows dynamic monitoring of hybridization events for HPV-16 and 18, has been a topic of focus by many researchers. In this systematic review, we highlight the route of development of DNA-based genosensory detection methods for diagnosis of high risk of HPV precancer. Biosensor detection methods of HPV-16 and 18 was investigated from 1994 to 2018 using several databases including PubMed, Cochrane Library, Scopus, Google Scholar, SID, and Scientific Information Database. Manual search of references of retrieved articles were also performed. A total of 50 studies were reviewed. By analyzing the most recent developed electrochemical biosensors for the identification of HPV, we observed that the sensor platform fabricated by Wang et al. holds the lowest detection limit reported in the literature for the DNA of HPV-16. Up to this date, optical, electrochemical, and piezoelectric systems are the main transducers used in the development of biosensors. Among the most sensitive techniques available to study the biorecognition activity of the sensors, we highlight the biosensors based fluorescent, EIS, and QCM. The current systematic review focuses on the sensory diagnostic methods that are being used to detect HPV-16 and 18 worldwide. Special emphasis is given on the sensory techniques that can diagnosis the individuals with CC. © 2018 BioFactors, 45(2):101-117, 2019.

The Role of microRNAs in the Viral Infections.

MicroRNAs (miRNAs) are non-coding RNAs with 19 to 24 nucleotides which are evolutionally conserved. MicroRNAs play a regulatory role in many cellular functions such as immune mechanisms, apoptosis, and tumorigenesis. The main function of miRNAs is the post-transcriptional regulation of gene expression via mRNA degradation or inhibition of translation. In fact, many of them act as an oncogene or tumor suppressor. These molecular structures participate in many physiological and pathological processes of the cell. The virus can also produce them for developing its pathogenic processes. It was initially thought that viruses without nuclear replication cycle such as Poxviridae and RNA viruses can not code miRNA, but recently, it has been proven that RNA viruses can also produce miRNA. The aim of this articles is to describe viral miRNAs biogenesis and their effects on cellular and viral genes.