Novel insights into the treatment of SARS-CoV-2 infection : An overview of current clinical trials

The emergence of the global pandemic caused by the novel SARS-CoV-2 virus has motivated scientists to find a definitive treatment or a vaccine against it in the shortest possible time. Current efforts towards this goal remain fruitless without a full understanding of the behavior of the virus and its adaptor proteins. This review provides an overview of the biological properties, functional mechanisms, and molecular components of SARS-CoV-2, along with investigational therapeutic and preventive approaches for this virus. Since the proteolytic cleavage of the S protein is critical for virus penetration into cells, a set of drugs, such as chloroquine, hydroxychloroquine, camostat mesylate have been tested in clinical trials to suppress this event. In addition to angiotensin-converting enzyme 2, the role of CD147 in the viral entrance has also been proposed. Mepolizumab has shown to be effective in blocking the virus's cellular entrance. Antiviral drugs, such as remdesivir, ritonavir, oseltamivir, darunavir, lopinavir, zanamivir, peramivir, and oseltamivir, have also been tested as treatments for COVID-19. Regarding preventive vaccines, the whole virus, vectors, nucleic acids, and structural subunits have been suggested for vaccine development. Mesenchymal stem cells and natural killer cells could also be used against SARS-CoV-2. All the above-mentioned strategies, as well as the role of nanomedicine for the diagnosis and treatment of SARS-CoV-2 infection, have been discussed in this review. (C) 2020 Elsevier B.V. All rights reserved.Peer reviewe

Human papillomavirus E5 protein, the undercover culprit of tumorigenesis

Abstract Human papillomavirus (HPV) is the most common viral infection of the reproductive tract worldwide. It has been well documented that the HPV oncoproteins E6 and E7 play important roles in cancer progression and maintenance. However, the high risk HPV E5 protein is also demonstrated to affect some cellular pathway and signaling in human cell lines. In this letter we argue for the need of further investigation and suggest that the HPV E5 protein should be acknowledged as an oncoprotein of HPV

Effect of equine herpesvirus type 1 (EHV-1) infection of nasal mucosa epithelial cells on integrin alpha 6 and on different components of the basement membrane

The respiratory mucosa is the common port of entry of equine herpesvirus type 1 (EHV-1) and several other alphaherpesviruses. An important prerequisite for successful host invasion of the virus is to cross the epithelial cell layer and the underlying basement membrane barrier. In the present study, an analysis was performed to see if an EHV-1 infection of nasal mucosa epithelial cells leads to damage of the underlying extracellular matrix proteins. Nasal mucosa explants were inoculated with EHV-1 and collected at 0, 24 and 48 hours post-inoculation (hpi). Then, double immunofluorescence staining was performed to detect viral-antigen-positive cells on the one hand and integrin alpha 6, laminin, collagen IV and collagen VII on the other hand. The area of these extracellular matrix proteins was measured in regions of interest (ROIs) at a magnification of 200X by means of the software imaging system ImageJ. ROIs were defined beneath uninfected and infected regions. In uninfected regions, 22-28 % of the ROI was stained for integrin alpha 6, 18-37 % for laminin, 14-38 % for collagen IV and 18-26 % for collagen VII. In infected regions, the percentage positive for integrin alpha 6 was significantly decreased to 0.1-9 % and 0.1-6 % after 24 and 48 hours of inoculation, respectively. Infection did not alter the percentages for laminin and collagen IV. For collagen VII, an increase in the percentage (from 18-26 % to 28-39 %) could be observed underneath EHV-1-infected plaques at 48 hours of inoculation. In conclusion, the results revealed a substantial impact of EHV-1 infection on integrin alpha 6 and collagen VII, two important components of the extracellular matrix, which are associated with the basement membrane and may facilitate virus penetration via hijacked leukocytes to underlying tissues

CRISPR–Cas system to discover host-virus interactions in Flaviviridae

Abstract The Flaviviridae virus family members cause severe human diseases and are responsible for considerable mortality and morbidity worldwide. Therefore, researchers have conducted genetic screens to enhance insight into viral dependency and develop potential anti-viral strategies to treat and prevent these infections. The host factors identified by the clustered regularly interspaced short palindromic repeats (CRISPR) system can be potential targets for drug development. Meanwhile, CRISPR technology can be efficiently used to treat viral diseases as it targets both DNA and RNA. This paper discusses the host factors related to the life cycle of viruses of this family that were recently discovered using the CRISPR system. It also explores the role of immune factors and recent advances in gene editing in treating flavivirus-related diseases. The ever-increasing advancements of this technology may promise new therapeutic approaches with unique capabilities, surpassing the traditional methods of drug production and treatment

A Perspective on Rabies in the Middle East—Beyond Neglect

Rabies is a neglected but preventable viral zoonosis that poses a substantial threat to public health. In this regard, a global program has been initiated for the elimination of human rabies caused by rabid dogs through the mass vaccination of canine populations. Geographic areas vary greatly towards attainment of this objective. For example, while dog-mediated and wildlife rabies have been largely controlled in major parts of the Americas and Western Europe, the Middle East still grapples with human rabies transmitted by unvaccinated dogs and cats. Rabies prevention and control in the Middle East is quite difficult because the region is transcontinental, encompassing portions of Africa, Asia, and Europe, while consisting of politically, culturally, and economically diverse countries that are often subject to war and unrest. Consequently, one over-riding dilemma is the misinformation or complete lack of rabies surveillance data from this area. This communication is an attempt to provide an overview of rabies in the Middle East, as a cohesive approach for the honing of disease management in each area, based on data compiled from multiple sources. In addition, the related regional transboundary movement of rabies was investigated through phylogenetic studies of available viral gene sequences. Thereafter, the epidemiological status of rabies was assessed for the region. Finally, localities were classified first by the Stepwise Approach towards Rabies Elimination framework and then categorized into four different groups based on management theme: “rabies free”; owned dog and domestic animal vaccination; community dog vaccination; and wildlife vaccination. The classification system proposed herein may serve as a baseline for future efforts. This is especially important due to the severe lack of rabies information available for the Middle East as a whole and a need for a comprehensive program focusing on the entirety of the region in light of renewed international commitment towards canine rabies elimination

Isolation and characterization of equine nasal mucosal CD172a⁺ cells

The nasal mucosa surface is continuously confronted with a broad variety of environmental antigens, ranging from harmless agents to potentially harmful pathogens. This area is under rigorous control of professional antigen presenting cells (APCs), such asdendritic cells (DCs) and macrophages. Mucosal APCs play a crucial role in inducing primary immune responses and the establishment of an immunological memory. In the present study, a detailed characterization of CD172a(+) cells, containing the APCs residing in the equine nasal mucosa was performed for the first time. CD172a(+) cells were isolated from collagenase-treated equine nasal mucosa fragments by MACS. Expression of surface markers was determined by flow cytometry and functional analysis was done by measuring the uptake of FITC conjugated ovalbumin (FITC-OVA). Cell surface phenotype of the isolated cells was as follows: 90% CD172a(+), 30% CD1c(+), 46% CD83(+), 42% CD206(+) and 28% MHC II+. This clearly differs from the phenotype of blood-derived monocytes: 96% CD172a(+), 4% CD1c(+), 11% CD83(+), 9% CD206(+), 72% MHC II+ and blood monocyte derived DCs: 99% CD172a(+), 13% CD1c(+), 30% CD83(+), 51% CD206(+) and 93% MHC II+. The CD172a(+) nasal mucosal cells were functionally able to endocytose FITC-OVA but to a lesser degree than monocyte-derived DCs. Together, these results demonstrate that the isolated CD172a(+) nasal mucosal cells resemble immature DCs in the nasal area. (C) 2013 Elsevier B.V. All rights reserved

siRNA-E6 sensitizes HPV-16-related cervical cancer through Oxaliplatin: an in vitro study on anti-cancer combination therapy

Abstract Background Persistent infection with high-risk Human papillomaviruses (HPV), such as hr-HPV-16 and hr-HPV-18, lead to cervical cancer, the fourth most common cancer in the world. In the present study, we investigated the alteration of E6 oncogene expression by E6-specific short interfering RNA (siRNA) combined with Oxaliplatin. Methods The cervical cancer cell line, CaSki, was transfected with E6-siRNA, then treated with Oxaliplatin. The cellular genes, such as p53, MMP9, Nanog, and caspases expression, were assessed by quantitative real-time PCR. The cell death rate, cell cycle, and cell viability were assessed by Annexin V/PI staining, DAPI staining, and MTT test, respectively. Furthermore, colony formation assay and scratch test determined the stemness ability and cell metastasis, respectively. Results Combination therapy increased the re-expression of genes involved in the p53-dependent apoptosis pathway (increase in apoptosis to 44.2%), and reduced stemness and metastasis ability compared to either siRNA or Oxaliplatin monotherapy. Together, our results demonstrate that E6-siRNA and Oxaliplatin combination increased the cervical cancer cells’ sensitivity to Oxaliplatin and decreased the survival rate, proliferation, and metastasis, and consequently escalated apoptosis rate, induced cell cycle arrest in the sub-G1 stage, and reduced the chemotherapy drug dosage. Conclusion Inhibition of E6 oncogene expression and subsequent E6-siRNA with Oxaliplatin combination therapy could be a novel strategy for cervical cancer treatment. Graphical Abstrac