Epidemic Viral Diseases Research Articles

Harnessing Antiviral Peptides as Means for SARS-CoV-2 Control

Several times during the past two decades, epidemic viral diseases created global challenges. Although many solutions have been proposed to deal with this tight spot, it is still believed that public vaccination represents the most effective strategy to handle it. So far, various kinds of vaccines including protein subunits, virus-like particles, inactivated, live attenuated, viral vectors, RNA, and DNA vaccines have been used in the prevention of COVID-19. Among the various categories of vaccines, peptide vaccines have created a new hope for quick and trustworthy access due to the development of proteomics equipment. This review specifically focuses on vaccines and peptide therapies in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). We consider here the efficacy and safety of subunit and synthetic peptides vaccine in clinical trial phases. Furthermore, monoclonal antibodies with the ability to suppress the development of SARS-CoV-2, those candidates that have entered into clinical trials until March 2023, were selected and evaluated.

Identifying cerebral microstructural changes in patients with COVID-19 using MRI: A systematic review.

Coronavirus disease 2019 (COVID-19) is an epidemic viral disease caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite the excessive number of neurological articles that have investigated the effect of COVID-19 on the brain from the neurological point of view, very few studies have investigated the impact of COVID-19 on the cerebral microstructure and function of the brain. The aim of this study was to summarize the results of the existing studies on cerebral microstructural changes in COVID-19 patients, specifically the use of quantitative volumetric analysis, blood oxygen level dependent (BOLD), and diffusion tensor imaging (DTI). We searched PubMed/MEDLINE, ScienceDirect, Semantic Scholar, and Google Scholar from December 2020 to April 2022. A well-constructed search strategy was used to identify the articles for review. Seven research articles have met this study's inclusion and exclusion criteria, which have applied neuroimaging tools such as quantitative volumetric analysis, BOLD, and DTI to investigate cerebral microstructure changes in COVID-19 patients. A significant effect of COVID-19 was found in the brain such as hypoperfusion of cerebral blood flow, increased gray matter (GM) volume, and reduced cortical thickness. The insula and thalamic radiation were the most frequent GM region and white matter tract, respectively, that are involved in SARS-CoV-2. COVID-19 was found to be associated with changes in cerebral microstructures. These abnormalities in brain areas might lead to be associated with behaviors, mental and neurological alterations that need to be considered carefully in future studies.

Ethnopharmacological Potential of Phytochemicals and Phytogenic Products against Human RNA Viral Diseases as Preventive Therapeutics.

RNA viruses have been the most destructive due to their transmissibility and lack of control measures. Developments of vaccines for RNA viruses are very tough or almost impossible as viruses are highly mutable. For the last few decades, most of the epidemic and pandemic viral diseases have wreaked huge devastation with innumerable fatalities. To combat this threat to mankind, plant-derived novel antiviral products may contribute as reliable alternatives. They are assumed to be nontoxic, less hazardous, and safe compounds that have been in uses in the beginning of human civilization. In this growing COVID-19 pandemic, the present review amalgamates and depicts the role of various plant products in curing viral diseases in humans.

Personalized approach to selecting probiotics in the post-COVID period

Summarizing the data from the follow-up of patients who underwent COVID-19 indicated that, unlike in case of other epidemic viral diseases, pathological symptoms and complaints associated with respiratory dysfunction after COVID-19 persist for a long time, for several weeks and months after the end of treatment. Recently, an important role in maintaining the homeostasis of the respiratory tract has been assigned to the intestinal microbiota, so the use of probiotics is a promising direction in the framework of complex rehabilitation measures in the post-COVID period. The purpose of the study: to identify probiotics with a proven effect on the correction of respiratory symptoms in order to develop a personalized approach to the selection of an optimal probiotic in the post-COVID period.

Classical swine fever virus infection suppresses claudin-1 expression to facilitate its replication in PK-15 cells

Classical swine fever (CSF) is one of the most epidemic viral diseases in swine industry. The causative pathogen is CSF virus (CSFV), a small enveloped RNA virus of Flaviviridae family. Claudin-1 was reported to be involved in the infections of a number of viruses, including many from Flaviviridae family, but no studies have investigated the role of porcine claudin-1 during CSFV infection in PK-15 cells. In this study, on the one hand, we demonstrated that CSFV infection reduced the claudin-1 expression at both mRNA and protein levels; on the other hand, CSFV infection was enhanced after claudin-1 knockdown, but inhibited by claudin-1 overexpression in a dose-dependent manner. Furthermore, negative correlation was demonstrated between the claudin-1 expression and CSFV titer. In conclusion, claudin-1 might be a barrier for CSFV infection in PK-15 cells, while CSFV bypasses the barrier through lysosome mediated degradation of claudin-1, which could be repressed by bafilomycin A1. Although the elaborate mechanisms how claudin-1 plays its roles in CSFV infection require further investigations, this study may advance our understanding of the molecular host–pathogen interaction mechanisms underlying CSFV infection and suggests enhancement of porcine claudin-1 as a potential preventive or therapeutic strategy for CSF control.

Compelling Evidence for the Activity of Antiviral Peptides against SARS-CoV-2.

Multiple outbreaks of epidemic and pandemic viral diseases have occurred in the last 20 years, including those caused by Ebola virus, Zika virus, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The emergence or re-emergence of such diseases has revealed the deficiency in our pipeline for the discovery and development of antiviral drugs. One promising solution is the extensive library of antimicrobial peptides (AMPs) produced by all eukaryotic organisms. AMPs are widely known for their activity against bacteria, but many possess additional antifungal, antiparasitic, insecticidal, anticancer, or antiviral activities. AMPs could therefore be suitable as leads for the development of new peptide-based antiviral drugs. Sixty therapeutic peptides had been approved by the end of 2018, with at least another 150 in preclinical or clinical development. Peptides undergoing clinical trials include analogs, mimetics, and natural AMPs. The advantages of AMPs include novel mechanisms of action that hinder the evolution of resistance, low molecular weight, low toxicity toward human cells but high specificity and efficacy, the latter enhanced by the optimization of AMP sequences. In this opinion article, we summarize the evidence supporting the efficacy of antiviral AMPs and discuss their potential to treat emerging viral diseases including COVID-19.

COVID-19 coronavirus: pathogenesis, clinical features, diagnostics, epidemiology, prevention and control

Spreading of the diseases from country to country and from continent to another is one of the drawbacks of globalization. In December 2019, from Wuhan in China, COVID-19 was emerged as a new viral disease caused by a novel betacoronavirus which spread in more than 210 countries and 3 continents over 3 months. “SARS-CoV-2” is the name of the virus while “Coronavirus Disease 2019” (COVID-19) is the disease itself. Coronaviruses cause a variety of diseases in birds and mammals ranging from mild upper respiratory disease to severe acute respiratory distress which may lead to death. The aim of this review is to provide a brief introduction to coronaviruses, demonstrate and describe clinical features, epidemiological, transmission mode, treatment and vaccination trials of COVID-19 globally and in Egypt, and an attempt to review the rapid identification and diagnostic features of this virus as well as summarize history of pandemic and epidemic viral diseases. We hope our review will provide the global community and the literature with the wise steps for controlling and preventing the outbreak of this severe pathogenic virus.

Simultaneous and rapid detection method for measles and rubella using single-tube multiplex real-time quantitative RT-PCR

Patients with measles or rubella infections manifest acute onset fever accompanying systemic exanthema, which are clinically difficult to be distinguish. Rapid diagnosis and differentiation of such epidemic viral diseases is essential to prevent outbreaks. We developed a single-tube multiplex real-time PCR assay for these indistinguishable viruses. We used previously-reported primer settings, with a slight modification of reporter dye, and applied to multiplex Taqman real-time PCR by cobas z480 (Roche Molecular Systems, Inc.). Consequently, the assay could detect 10 copies/10 μl of measles and rubella with coefficient of variations of 11.2% and 21.8%, respectively. Strengths of our methodology include simplicity of operation, short measurement time (2 h), uses of internal control (confirming a run of PCR), and quantitative measurement with high sensitivity. Both measles and rubella currently cause social outbreaks in Japan. We hope that our single-tube multiplex assay contributes to an early diagnosis, leading to an appropriate infection control measure and prevention of epidemics.

Vaccination strategy for epidemic viral diseases in healthcare workers: Cut-off for optimal immunization.

Healthcare workers (HCWs) are at an increased risk of being exposed to epidemic viral diseases (EVDs), such as measles, rubella, mumps, and varicella-zoster. Currently, in case of the absence of written records on previous immunizations, the Japanese Society for Infection Prevention and Control guidelines require HCWs to have antibody titers higher than laboratory thresholds, possibly leading to over-immunization. We report our vaccination strategy and the consequent incidences of EVDs at the Osaka University Hospital between 2000 and 2016. In 2001, we initiated an annual serology check of antibody titers against EVDs and immunization for newly employed HCWs. As an additional vaccination program, all HCWs with low antibody titers were vaccinated in 2005 and 2010. Antibody titers were determined by an enzyme immunoassay (EIA), with a positive range of >2.0 cut-off index. After implementing the vaccination strategy to keep the laboratory threshold, there were only sporadic cases of EVDs among HCWs. More than 99% of individuals who had positive titers in 2005 remained the positive antibody titers in 2010, indicating that a minimum interval of 5 years is enough to measure immunity. Unprotected workers can, even silently, transmit the contagious viruses to patients and coworkers, possibly resulting in a nosocomial outbreak. However, over-vaccination may yield adverse effects and financial burdens. Our observational data indicate that the laboratory cut-off index of >2.0 by EIA may provide a sufficient herd immunity to prevent EVDs among HCWs.

MULTIFACETED CHIKUNGUNYA INFECTION IN INFANTS - A CASE SERIES

Chikungunya is an epidemic viral disease. It is known to cause explosive outbreaks after disappearing for several years. The clinical manifestations among infants are entirely different as compared to adults and older children. It can go undiagnosed in the garb of sepsis unless strong clinical suspicion is present. We report a series of infants presenting with neurological, circulatory, and cutaneous manifestations. Key words: Chikungunya, Infants, Meningoencephalitis, Transaminitis

T-bet-mediated Tim-3 expression dampens monocyte function during chronic hepatitis C virus infection.

Hepatitis C virus (HCV) induces a high rate of chronic infection via dysregulation of host immunity. We have previously shown that T-cell immunoglobulin and mucin domain protein-3 (Tim-3) is up-regulated on monocyte/macrophages (M/Mφ) during chronic HCV infection; little is known, however, about the transcription factor that controls its expression in these cells. In this study, we investigated the role of transcription factor, T-box expressed in T cells (T-bet), in Tim-3 expression in M/Mφ in the setting of HCV infection. We demonstrate that T-bet is constitutively expressed in resting CD14+ M/Mφ in the peripheral blood. M/Mφ from chronically HCV-infected individuals exhibit a significant increase in T-bet expression that positively correlates with an increased level of Tim-3 expression. Up-regulation of T-bet is also observed in CD14+ M/Mφ incubated with HCV+ Huh7.5 cells, as well as in primary M/Mφ or monocytic THP-1 cells exposed to HCV core protein invitro, which is reversible by blocking HCV core/gC1qR interactions. Moreover, the HCV core-induced up-regulation of T-bet and Tim-3 expression in M/Mφ can be abrogated by incubating the cells with SP600125-an inhibitor for the c-Jun N-terminal kinase (JNK) signalling pathway. Importantly, silencing T-bet gene expression decreases Tim-3 expression and enhances interleukin-12 secretion as well as signal transducer and activator of transcription 1 phosphorylation. These data suggest that T-bet, induced by the HCV core/gC1qR interaction, enhances Tim-3 expression via the JNK pathway, leading to dampened M/Mφ function during HCV infection. These findings reveal a novel mechanism for Tim-3 regulation via T-bet during HCV infection, providing new targets to combat this global epidemic viral disease.

The role of pre-existing cross-reactive antibodies in determining the efficacy of vaccination in humans: study protocol for a randomized controlled trial.

BackgroundEpidemic viral diseases have become more prevalent.. Among the various strategies to prevent such epidemics, vaccination is the most cost-effective. However, populations that are immunized are typically already exposed to multiple previous vaccinations or natural infections. Studies from this and other laboratories have revealed that pre-existing dengue antibodies can either inhibit or enhance subsequent dengue infection depending on the pre-existing antibody levels. While cross-reactive antibody is potentially pathogenic in dengue, how it impacts immune response to vaccination is unclear. Aggregated at the site of vaccination and the respective draining lymph nodes are antigen-presenting and immune regulatory cells that express Fc receptors and play pivotal roles in determining the magnitude and polarity of the immune response. Vaccine uptake by these antigen-presenting cells may thus be either inhibited or enhanced when vaccines are opsonized with cross-reactive antibodies.DesignIn view of the limited knowledge on how cross-reactive antibodies affect vaccination outcome, we propose a study that exploits the known cross reactivity between Japanese encephalitis (JE) virus antibody and yellow fever (YF) vaccine. We hypothesize that cross-reactive antibodies impact antibody response to YF at the point vaccination in a concentration-dependent manner by altering both vaccine uptake and the innate immune response by antigen presenting cells. We will structure an open-label clinical trial on sequential vaccination with JE and YF vaccines, with different time intervals between vaccinations. This would test immune response to YF vaccination in subjects with different titer of cross-reactive JE vaccine-derived antibodies. The clinical materials obtained in the trial will drive basic laboratory investigations directed at elucidating how heterologous antibody affect vaccination at the molecular level. YF neutralizing antibody titer will be measured using plaque reduction neutralization test against the vaccine strain YF17D. Innate immune response will be characterized genetically using either microarray or digital PCR (or both). The innate immune response will also be characterized at the protein and metabolite level using Luminex bead technology and lipidomic/metabolomic approaches.DiscussionThis proposed study represents one of the first to examine the role of cross-reactive antibodies in modulating immune responses to vaccines, the findings of which may re-shape vaccination strategy.Trial registrationClinical Trials.gov registration number: NCT01943305 (3 September 2013).

Production and evaluation of antimycotic and antihepatitis C virus potential of fusant MERV6270 derived from mangrove endophytic fungi using novel substrates of agroindustrial wastes.

Among forty endophytic fungal isolates derived from the mangrove plant Avicennia marina, thirty-seven isolates (92.5 %) shown vary antimycotic activity against clinical Trichophyton, Microsporum, and Epidermophyton isolates. The hyperactive wild antagonistic strains Acremonium sp. MERV1 and Chaetomium sp. MERV7 were subjected to intergeneric protoplast fusion technique, and out of 20 fusants obtained, the fusant MERV6270 showed the highest antimycotic activity with the broadest spectrum against all dermatophytes under study. Solid-state fermentation (SSF) showed its superiority for antimycotic/antiviral metabolite production using cost-effective agroindustrial residues. Low-cost novel fermentation medium containing inexpensive substrate mixture of molokhia stalk, lemon peel, pomegranate peel, peanut peel (2:1:1:1) moistened with potato, and meat processing wastewaters (2:1, at moisture content of 60 %) provided a high antimycotic metabolite yield, 33.25 mg/gds, by the fusant MERV6270. The optimal parameters for antimycotic productivity under SSF were incubation period (4 days), incubation temperature (27.5-30 °C), initial pH (6), initial moisture level (60 %), substrate particle size (1.0 mm), and inoculum size (2 × 10(6) spores/gds), which elucidated antimycotic activity to 44.19 mg/gds. Interestingly, wild mangrove Acremonium sp. MERV1 and Chaetomium sp. MERV7 strains and their fusant MERV6270 showed significant inhibition of hepatitis C virus with viral knockdown percent of -82.48, -82.44, and -97.37 %, respectively, compared to the control (100 %), which open a new era in combat epidemic viral diseases.

Dengue virus serotype 2 and 3 causing high morbidity and mortality in Swat, Pakistan

Dengue, an alarmingly growing epidemic viral disease is a major health concern. Pakistan suffered several mini and major outbreaks of dengue over the past couple of years with high morbidity rates than those commonly reported from dengue epidemics globally. Hundreds of people died in the string of dengue epidemics in Pakistan since 2005. In July 2013, a major outbreak of dengue started in Swat district of Khyber Pakhtunkhwa (KPK) which has so far caused 57 deaths and thousands of morbidities. In this study, we screened 414 clinically diagnosed dengue patients for dengue specific antibodies, out of which 366 were found to be serologically positive by the Standard Diagnostics (SD) Dengue Duo test. All dengue virus (DENV) positive samples were then analyzed using a DENV serotype-specific reverse transcriptase polymerase chain reaction to identify the DENV serotypes present and to figure out active infections. In this study, 28.69% (105/366) of the serologically positive patients had active infection and DENV type 3 (DENV-3) was the most abundant serotype followed by DENV-2; similar to the outbreak in Punjab during 2010-11. The mortality rate from this epidemic to date has however been lower compared to the previous major DENV outbreak of 2010-11 in Lahore.

Advances in antiviral vaccine development.

Antiviral vaccines have been the most successful biomedical intervention for preventing epidemic viral disease. Vaccination for smallpox in humans and rinderpest in cattle was the basis for disease eradication, and recent progress in polio eradication is promising. Although early vaccines were developed empirically by passage in live animals or eggs, more recent vaccines have been developed because of the advent of new technologies, particularly cell culture and molecular biology. Recent technological advances in gene delivery and expression, nanoparticles, protein manufacturing, and adjuvants have created the potential for new vaccine platforms that may provide solutions for vaccines against viral pathogens for which no interventions currently exist. In addition, the technological convergence of human monoclonal antibody isolation, structural biology, and high-throughput sequencing is providing new opportunities for atomic-level immunogen design. Selection of human monoclonal antibodies can identify immunodominant antigenic sites associated with neutralization and provide reagents for stabilizing and solving the structure of viral surface proteins. Understanding the structural basis for neutralization can guide selection of vaccine targets. Deep sequencing of the antibody repertoire and defining the ontogeny of the desired antibody responses can reveal the junctional recombination and somatic mutation requirements for B-cell recognition and affinity maturation. Collectively, this information will provide new strategic approaches for selecting vaccine antigens, formulations, and regimens. Moreover, it creates the potential for rational vaccine design and establishing a catalogue of vaccine technology platforms that would be effective against any given family or class of viral pathogens and improve our readiness to address new emerging viral threats.

Epidemic viral diseases of wildlife ? sudden death in tammar wallabies, blind kangaroos, herpesviruses in pilchards ? what next?

In Australia the impact of European settlement on the indigenous human population and on flora and fauna is inevitably the subject of ongoing speculation. Major changes have occurred as a result of urban and rural developments and the introduction of agricultural practices which collectively impact on the environment and ecosystems especially through land clearing, water use and modification of water courses and water catchments. From both a human and animal health perspective, the changes as viewed by the general public are perhaps not always apparent but the impacts are no less significant. A range of microbial pathogens, parasites and other pests have been introduced to populations that often have not encountered these challenges before. Our indigenous wildlife populations have not been immune from these threats. And, if we include aquatic as well as terrestrial species of ?wildlife?, and venture to our immediate coastline, in recent years there has been profound evidence of the impact that follows the introduction of an exotic pathogen.

Plasma Concentration of Atrial Natriuretic Peptide in Different Phases of Korean Hemorrhagic Fever

Korean hemorrhagic fever (KHF) is an epidemic viral disease characterized by high fever, hemorrhagic tendency and renal failure, and by hemorrhages of right atrium and renal medulla as well as necrosis of anterior hypophysis. Plasma immunoreactive atrial natriuretic peptide (irANP) levels of 15 patients in the oliguric phase was 94.8 +/- 8.4 pg/ml (mean +/- SEM), 80% higher than of the normal control group (53.0 +/- 4.7 pg/ml; n = 28). In the diuretic phase it declined to 63.7 +/- 5.3 pg/ml (n = 26). Plasma renin activity (PRA) in the oliguric phase was 19.0 +/- 1.3 ng AI/ml/h, and in the diuretic phase 5.3 +/- 0.9 ng AI/ml/h, significantly higher than the control value (2.5 +/- 0.1 ng AI/ml/h). Elevations of irANP and PRA were not correlated in each group. Also systemic blood pressure as well as heart beats were significantly increased in the oliguric phase. These findings suggest that the increased irANP may have resulted from increased circulatory volume and that the ANP secretory process may not be affected by the disease.

Pathogenesis and transmission of AIDS

AIDS is a slow virus disease caused by a lentivirus. The silent incubation period following infection usually lasts many years, during which the infected person is potentially infectious to others. Pathological changes accumulate imperceptibly. When major symptomatic disease develops it is eventually fatal. The epidemic spread of the virus is new in Africa, as well as in North America and Europe. Twenty-five per cent of people infected with the virus die within seven years of infection. The ultimate mortality 20 years after infection cannot yet be known, but it may turn out to be close to 100 per cent. It is already apparent that AIDS is the most lethal epidemic viral disease of humans known to medical science. Flaws in the generally accepted hypothesis that AIDS is a sexually transmitted infection are exposed. It has been, characteristically, a blood-borne infection in the early years of the epidemic. However, the AIDS virus is exceptionally unstable genetically and it is probable that means of transmission more efficient than through blood have already developed.

Rift Valley Fever Caused the Fifth Plague of Egypt and That of 1977

To the Editor.— Gombert et al1suggested that the Fifth Plague of Egypt (Exodus 9:3-6) was caused by babesiosis. Subsequently, Jacoby2mentioned more likely candidates for the plague, namely, epidemic viral diseases such as foot and mouth disease and rinderpest. It should, however, be emphasized that the Bible mentions a wide spectrum of animal species that were severely affected and died due to the very grievous murrain, namely, cattle which is in the field, horses, asses, camels, oxen and sheep (Exodus 9:3). The two viral diseases suggested by Jacoby do not affect the complete range of the mentioned species. Both viruses are not pathogenic for horses and asses; rinderpest does not affect camels. More likely candidates are anthrax, as suggested by Shoshan,3and Rift Valley fever (RVF), as suggested by me.4There are some factors supporting the candidacy of RVF, an insect-borne zoonosis confined to the

The Fifth Plague of Egypt

To the Editor.— The article by Gombert et al (1982;248:3005) suggests that the Fifth Plague of Egypt (Exodus 9:3-6) was caused by babesiosis. The plague is described as "a great murrain... and all the cattle of Egypt died." Babesiosis is caused by an intraerythrocytic protozoan and is insect borne. It would, therefore, not occur as a sudden massive epidemic. The most likely candidates for causing the plague are epidemic viral diseases, foot and mouth disease, and rinderpest; the latter two may occur as explosive outbreaks with mortality rates of up to 50%. Foot and mouth disease occurs throughout the world. Rinderpest is believed to have originated in eastern Europe or Asia and reached Africa in the second half of the 19th century. However, a prior epidemic of rinderpest cannot be excluded. The fact that neither of these diseases affects man is another argument in their favor.