Viral Lesions Research Articles

Controlling viral inflammatory lesions by inhibiting fatty acid metabolism

Herpes simplex virus infection is a major cause of vision loss in humans. Eye damaging consequences are often driven by inflammatory cells as a result of an immune response to the virus. In the present report, we have compared the effect of inhibiting energy metabolism with etomoxir (Etox), which acts on the fatty acid oxidation pathway and 2-Deoxy-d-glucose (2DG), which acts on glycolysis for their inhibitory effects on herpetic ocular lesions. Both drugs showed similar protective effects when therapy was started on the day of infection, but some 2DG recipients succumbed to encephalitis. In contrast, all Etox recipients remained healthy. Both drugs were compared for effects on inflammatory reactions in the trigeminal ganglion (TG), where virus replicates and then establishes latency. Results indicate that 2DG significantly reduced CD8 and CD4 Th1 T cells in the TG, whereas Etox had minimal or no effect on such cells, perhaps explaining why encephalitis occurred only in 2DG recipients. Unlike treatment with 2DG, Etox therapy was largely ineffective when started at the time of lesion expression. Reasons for the differential effects were discussed as was the relevance of combining metabolic reprogramming approaches to combat viral inflammatory lesions.

Codon Pair Deoptimization (CPD)-Attenuated PRRSV-1 Vaccination Exhibit Immunity to Virulent PRRSV Challenge in Pigs.

Commercially used porcine respiratory and reproductive syndrome (PRRS) modified live virus (MLV) vaccines provide limited protection with heterologous viruses, can revert back to a virulent form and they tend to recombine with circulating wild-type strains. Codon pair deoptimization (CPD) is an advanced method to attenuate a virus that overcomes the disadvantages of MLV vaccines and is effective in various virus vaccine models. The CPD vaccine against PRRSV-2 was successfully tested in our previous study. The co-existence of PRRSV-1 and -2 in the same herd demands protective immunity against both viruses. In this study, live attenuated PRRSV-1 was constructed by recoding 22 base pairs in the ORF7 gene of the E38 strain. The efficacy and safety of the CPD live attenuated vaccine E38-ORF7 CPD to protect against virulent PRRSV-1 were evaluated. Viral load, and respiratory and lung lesion scores were significantly reduced in animals vaccinated with E38-ORF7 CPD. Vaccinated animals were seropositive by 14 days post-vaccination with an increased level of interferon-γ secreting cells. In conclusion, the codon-pair-deoptimized vaccine was easily attenuated and displayed protective immunity against virulent heterologous PRRSV-1.

Photodynamic Therapy Used to Treat an HIV Patient with an Efflorescence of Viral Warts after HAART Therapy

Healing from viral warts lesions can be hard to achieve in immunocompromised subjects like HIV-positive patients. The therapeutic target in immunocompetent subjects can be reached using different methods, including topical ointments, cryotherapy, laser therapy, imiquimod, and photodynamic therapy (PDT). We present a case of a male HIV-positive patient who came to the Dermatology department with multifocal wart lesions on his face, auricular, and retro-auricular areas after treatment with highly active antiretroviral therapy (HAART). In our case, surprisingly, only one session of PDT proved to induce complete regression of lesions which, despite their thickness, had a much more robust response to treatment than we could have possibly expected. After a brief review of the literature, it is possible to state that PDT revealed itself to be a valid option in immunocompromised patients who have a major risk of relapse.

A Synthetic SARS-CoV-2-Derived T-Cell and B-Cell Peptide Cocktail Elicits Full Protection against Lethal Omicron BA.1 Infection in H11-K18-hACE2 Mice.

Emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developing the capacity for immune evasion and resistance to existing vaccines and drugs. To address this, development of vaccines against coronavirus disease 2019 (COVID-19) has focused on universality, strong T cell immunity, and rapid production. Synthetic peptide vaccines, which are inexpensive and quick to produce, show low toxicity, and can be selected from the conserved SARS-CoV-2 proteome, are promising candidates. In this study, we evaluated the effectiveness of a synthetic peptide cocktail containing three murine CD4+ T-cell epitopes from the SARS-CoV-2 nonspike proteome and one B-cell epitope from the Omicron BA.1 receptor-binding domain (RBD), along with aluminum phosphate (Al) adjuvant and 5' cytosine-phosphate-guanine 3' oligodeoxynucleotide (CpG-ODN) adjuvant in mice. The peptide cocktail induced good Th1-biased T-cell responses and effective neutralizing-antibody titers against the Omicron BA.1 variant. Additionally, H11-K18-hACE2 transgenic mice were fully protected against lethal challenge with the BA.1 strain, with a 100% survival rate and reduced pulmonary viral load and pathological lesions. Subcutaneous administration was found to be the superior route for synthetic peptide vaccine delivery. Our findings demonstrate the effectiveness of the peptide cocktail in mice, suggesting the feasibility of synthetic peptide vaccines for humans. IMPORTANCE Current vaccines based on production of neutralizing antibodies fail to prevent the infection and transmission of SARS-CoV-2 Omicron and its subvariants. Understanding the critical factors and avoiding the disadvantages of vaccine strategies are essential for developing a safe and effective COVID-19 vaccine, which would include a more effective and durable cellular response, minimal effects of viral mutations, rapid production against emerging variants, and good safety. Peptide-based vaccines are an excellent alternative because they are inexpensive, quick to produce, and very safe. In addition, human leukocyte antigen T-cell epitopes could be targeted at robust T-cell immunity and selected in the conserved region of the SARS-CoV-2 variants. Our study showed that a synthetic SARS-CoV-2-derived peptide cocktail induced full protection against lethal infection with Omicron BA.1 in H11-K18-hACE2 mice for the first time. This could have implications for the development of effective COVID-19 peptide vaccines for humans.

The Role of Ellagic Acid and Annona muricata in the Management of Human Papillomavirus (HPV)-Related Genital Lesions: A Systematic Review

Background: Several reports highlighted the role of nutraceutical compounds in the prevention and management of HPV-related genital lesions both in men and women, with interesting results. Here, we reviewed the effect of ellagic acid and Annona muricata for managing HPV-related genital lesions. Methods: Relevant databases were searched by using methods recommended by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The primary endpoint was the clinical cure, defined as the clinical and/or laboratory and/or histopatologically demonstrated absence of HPV-related lesions at the end of the treatment. Results: We enclosed two retrospective studies, two prospective studies and one randomized controlled trial. In men, ellagic acid and Annona muricata complex improves seminal parameters and HPV-DNA clearance. In women, it has a chemopreventive action in cervical cancer and increases the HPV viral clearance. No clinically significant adverse effects have been reported. Conclusions: In conclusion, the combination of ellagic acid and Annona muricata shows interesting and promising results in terms of HPV viral clearance and HPV related genital lesions. However, more data are necessary to confirm these results.

Painful facial, oral, and genital ulcers

Painful facial, oral, and genital ulcers

High Levels of Extracellular Potassium Can Delay Myxoma Virus Replication by Preventing Release of Virions from the Endosomes.

Potassium (K+) is one of the most abundant cations in the human body. Under normal conditions, the vast majority of K+ is found within cells, and the extracellular [K+] is tightly regulated to within 3.0 to 5.0 mM. However, it has recently been shown that high levels of localized necrosis can increase the extracellular concentration of K+ to above 50 mM. This raises the possibility that elevated extracellular K+ might influence a variety of biological processes that occur within regions of necrotic tissue. For example, K+ has been shown to play a central role in the replication cycles of numerous viral families, and in cases of lytic infection, localized regions containing large numbers of necrotic cells can be formed. Here, we show that the replication of the model poxvirus myxoma virus (MYXV) is delayed by elevated levels of extracellular K+. These increased K+ concentrations alter the cellular endocytic pathway, leading to increased phagocytosis but a loss of endosomal/lysosomal segregation. This slows the release of myxoma virus particles from the endosomes, resulting in delays in genome synthesis and infectious particle formation as well as reduced viral spread. Additionally, mathematical modeling predicts that the extracellular K+ concentrations required to impact myxoma virus replication can be reached in viral lesions under a variety of conditions. Taken together, these data suggest that the extracellular [K+] plays a role in determining the outcomes of myxoma infection and that this effect could be physiologically relevant during pathogenic infection. IMPORTANCE Intracellular K+ homeostasis has been shown to play a major role in the replication of numerous viral families. However, the potential impact of altered extracellular K+ concentrations is less well understood. Our work demonstrates that increased concentrations of extracellular K+ can delay the replication cycle of the model poxvirus MYXV by inhibiting virion release from the endosomes. Additionally, mathematical modeling predicts that the levels of extracellular K+ required to impact MYXV replication can likely be reached during pathogenic infection. These results suggest that localized viral infection can alter K+ homeostasis and that these alterations might directly affect viral pathogenesis.

Цитоморфологическая диагностика инфекционных заболеваний женской половой сферы с позиции персонализированной медицины

To date, the course of urogenital infections is characterized by asymptomatic or erased forms, but sexually transmitted infections (STIs) do not become less dangerous and can cause severe complications such as infertility, ectopic pregnancy, chronic diseases, intrauterine fetal damage, congenital pathology and diseases in newborn children. Taking into account the extreme urgency of the problem of timely diagnosis and adequate correction of endocervix pathology, the lack of clear cytomorphological parallels with clinical data, a very significant practical and scientific interest is the comparison of the results of cytomorphological research with diagnostic data using polymerase chain reaction. This will expand the possibilities of interpreting the cytological method as a primary study for further diagnosis and treatment. Аim: to analyze the results of cytomorphological studies of the urogenital tract of women with sexually transmitted infections of various etiologies and to assess their significance for a personal approach to treatment. Design: Prospective cohort study. Materials and methods. For a comprehensive cytomorphological study, data on 335 female patients (mean age 31.6 ± 8.2 years) with uncomplicated urogenital chlamydia (n = 18), papillomavirus (n = 97), herpetic (n = 26), mycotic (n = 41) infections, trichomoniasis (n = 12) and mixed forms were analyzed infectious lesion (n = 141). Results. If there is a history of STIs, it becomes necessary to identify concomitant genital infections and vaginal dysbiosis. It is difficult to determine which pathogen caused the "launch" of inflammatory reactions, and which one joined a second time and aggravated the course of the disease. A combination of candidiasis and chlamydial infection, candidiasis and viral lesions, chlamydial infection and viral lesions is possible, therefore, in addition to molecular genetic and serological diagnostics, cytomorphological methods are necessary for the diagnosis of STIs. Conclusion. The modern cytomorphological methods used for the diagnosis of infections of the female genital sphere allow us to quickly and reliably determine the type of pathogen and the nature of the process, which could help clinicians to choose the appropriate therapy correctly, to prevent the transition of the disease to the chronic stage, to avoid complications and the development of neoplastic processes. Keywords: cytomorphological diagnostics, sexually transmitted infections, traditional cytology, liquid cytology, personalized medicine.

Сочетание инфекционных осложнений у пациента с иммуносупрессией (клинический случай)

Against the background of high incidence of new coronavirus infection there is a widespread increase in the incidence of co-infections, in particular, with HIV infection. Difficulties of differential diagnosis of infectious diseases in such a situation are similar clinical picture, similar radiological changes in the lungs (primarily with pneumocystis pneumonia and viral lesions caused by SARS-CoV-2), reduced availability of medical diagnostic procedures in a pandemic. The presented clinical case demonstrates a rare combination of co-infection - COVID-19, pneumocystis pneumonia and tuberculosis - in a patient with human immunodeficiency virus; the course of these infectious complications is described. A patient with a low level of CD4+ -T - lymphocytes, a high viral load, concomitant renal and hepatic pathology had long-term persistence of SARS-CoV-2 (longcoid). The presence of a "trio" of infectious diseases made timely diagnosis of tuberculosis difficult. During the COVID-19 pandemic, surveillance of individuals living with HIV should include a spectrum of investigations to rule out tuberculosis and opportunistic infections, especially in individuals with low CD4 cell counts, high viral load, lack of antiretroviral therapy, and clinical improvement with standard COVID-19 therapy for timely therapy and reduced mortality in such patients.

Эндотелиальная дисфункция как явление краткосрочных и долгосрочных патологических эффектов при вирусном поражении SARS-CoV-2

Despite the relatively low mortality rate, SARS-CoV-2 infection is characterized by the presence of a number of complications that significantly affect the life of recovered patients. Thorough analysis of coronavirus infection mechanisms shows that endothelial dysfunction plays a key role in the development of the disease and long-term symptoms. Endothelial damage is associated with the occurrence of a number of long-term symptoms affecting various organ systems in infected patients. Also the existing polymorbidity (hypertension, obesity, diabetes mellitus, oncological and chronic respiratory diseases) in a patient with a new coronavirus infection are risk factors for a severe course of the disease development. The mutual burden of various pathologies in the potentiation of the development of new abnormalities makes it relevant to further study of endothelial dysfunction in SARS-CoV-2. The purpose of this research is to analyze current scientific data within the framework of understanding the causes of short-term and long-term pathologies associated with vascular endothelial dysfunction in SARS-CoV-2 viral lesion. Materials and methods of research: we analyze international modern scientific publications on endothelial damage in COVID-19 and its complications. Conclusion: a scientific research based on modern literature data allows to propose promising treatment strategies that can save patients from long-term complications.

КОВІД-19-АСОЦІЙОВАНІ ЗМІНИ ІМУНИТЕТУ ТА УРАЖЕННЯ ЛЕГЕНЬ

The review of the literature presents basic data on the mechanisms of pathogenesis of a new viral COVID-19 infection: viral damage, immune dysfunction, endothelial lesions. The features of immunological changes in the COVID-19-associated conditions of different severity and genesis of pulmonary lesions have been described. The results of studies on the features of pulmonary pathology in viral lung lesions, acute respiratory distress syndrome, chronic obstructive lung disease, interstitial pulmonary fibrosis, bronchial asthma, active and latent pulmonary tuberculosis have been presented. Additionally, some pathological mechanisms leading to the formation of long-term disease and persistent changes in the lungs after COVID-19 (fibrosis, bronchiectasis, obstructive bronchiolitis, pulmonary thromboembolism) have been outlined. The autoimmune complications due to this viral infection and vaccination against COVID-19, the features of vaccine-induced immunity and the role of crossimmunological reactivity have been reviewed. Key words: COVID-19, SARS-CoV-2 virus, pathogenesis, immunity, lung damage.

Некоторые особенности возбудителей гепатитов Е

The priority of discovering the causative agent of hepatitis E in humans belongs to our compatriot M.S.Balayan, who proved the role of the virus in the occurrence of so-called hepatitis of unknown etiology in experiments with self-infection with fecal filtrate from these patients. After more than three decades, the problem of viral hepatitis of unknown etiology remains relevant, including due to the poor awareness of doctors of all specialties about the course of acute and chronic hepatitis E, its spread, as well as the possibilities of laboratory diagnosis of this disease. Hepatitis E virus can exit in two forms: quasi-enveloped (eHEV) in serum and nonenveloped (neHEV) in bile, feces and environment. HEV is geterogenic and it is divided into 8 genotypes, which determine causative agent, rout of transmission, severity of disease, risk group and geographical location. The study of the genetic and cultural characteristics of various genotypes and subtypes of the causative agent of hepatitis E and its distribution requires further development, which is impossible without the vigilance of doctors when examining patients with viral hepatitis of unclear etiology and using available laboratory methods to confirm the etiology of viral liver lesions. Key words: hepatitis E virus, eHEV, neHEV, 8 genotypes, risk groups, geographical location

Опыт использования синдромальных подходов к диагностике респираторных инфекций

Irrational or excessive use of antibiotics, the absence or insufficient use of rapid diagnostics tests at the point of care ("POC"), as well as insufficient infection control are key factors in the development of multi- and pan-resistance to antibiotics. The article presents the clinical experience of using the syndromic approach Patients and methods. The work was carried out on the basis of the Morozovskaya State children's hospital from February to June 2022 in accordance with the standards of medical care for patients with acute respiratory infections using multiplex PCR test (mPCR) – BioFire FilmArray respiratory panel (BioFire RP). The study included inpatient children (n = 40) with symptoms of acute respiratory infections and respiratory failure (DN) of different severity. Results. The analysis of the nosological structure showed that acute obstructive bronchitis/acute bronchitis (J20.9) was found in 47.5%, pneumonia (J18.9) in 20% of children, acute bronchiolitis (J21.9) at 7.5%, other viral lesions of the respiratory tract (J00-J06) – 25%. The standard PCR ARVI panel identified pathogens in 45% (n = 18), the BioFire RP panel in 55% (n = 22) of patients (p = 0.503). An important indicator is the speed of obtaining results. The median time from the moment of taking the smear to the moment of transmitting the result to the physician was 2.56 hours (CI: 1.91–3.62) when examined using the BioFire RP panel compared with 28.4 hours (CI: 9.64–33) when using standard PCR diagnostics for respiratory viruses (p < 0.001). Conclusion. Methods of rapid molecular diagnostics can reduce the time of hospitalization of patients. In the study, the duration of hospitalization is 1 day shorter compared to the analysis of retrospective indicators of hospitalization terms. This is due to the ability to quickly identify the agent of respiratory infection, which in turn affects the tactics of treatment, optimizes the appointment of antibiotics, which affects to the duration of hospitalization. Key words: respiratory infection, BioFire, PCR, virus, rapid diagnosis, etiotropic therapy

Mahuang Xixin Fuzi decoction protects the BALB/c-nude mice infected with influenza A virus by reducing inflammatory cytokines storm and weakly regulating SIgA immune response

Mahuang Xixin Fuzi Decoction (MXF), as a classical prescription of traditional Chinese medicine (TCM), has been used to treat the immunocompromised individuals infected with influenza A virus (IAV). The study aims to explore the regulatory of MXF on inflammation and secretory immunoglobulin A (SIgA) antibodies immune response in BALB/c-nude mice infected with IAV. The BALB/c-nude mice were infected with IAV, then different dosages of MXF were orally administrated to the mice. The weight, rectal temperature, spontaneous activity, spleen index, lung index, pathological changes of lung tissues, and the relative mRNA expression level of H1N1 M gene were measured for the purpose of valuing the antiviral effect of MXF. The expression levels of cytokines in lungs and immunoglobulin A (IgA) in serum of BALB/c-nude mice were determined with Cytometric Bead Array System (CBA). SIgA in bronchoalveolar lavage fluids (BALF) was detected with Enzyme-linked Immunosorbent Assay (ELISA). The mRNA and protein expression levels of B cell activating factor (BAFF), chemokine receptors 10 (CCR10), and polymeric immunoglobulin receptor (pIgR) in the lung tissues, which are related to the secretion of SIgA, were determined by using RT-PCR and Western blot. MXF could alleviate the clinical features and reduce the severity of viral lung lesions, including improving the body weight, rectal temperature and spontaneous activity of nude mice infected with IAV, increasing spleen index, decreasing lung index, alleviating pathological damage, and decreasing the relative expression level of H1N1 M gene. Levels of pro-inflammatory cytokines, including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), interleukin-12p70 (IL-12p70), and interleukin-17A (IL-17A) were also significantly decreased after treatment with MXF. Interferon-γ (IFN-γ), an antiviral cytokine, was significantly up-regulated in high dose MXF (3.12g/kg) group. Moreover, after MXF treatment, the expressions of SIgA in BALF and IgA in serum were both at relatively low levels. And the mRNA and protein expressions of BAFF, CCR10, and pIgR were significantly decreased after treatment with MXF. MXF has obviously protective effects on BALB/c-nude mice infected with IAV by inhibiting virus replication, calming inflammatory cytokine storm, and regulating SIgA immune response weakly.

COVID-19 and antimicrobial therapy

BACKGROUND: One of the problems with managing patients with a new coronavirus infection is the irrational use of antibiotics. Antibacterial drugs are not active against viral infection, including COVID-19. Unfortunately, in actual clinical practice, the level of antibiotic use remains extremely high, reaching 7080%. Unwanted antibacterial therapy leads to a number of undesirable phenomena that can significantly worsen the patients condition, and sometimes lead to life-threatening consequences. In this context, the most important question is the formulation of the diagnosis. In particular, the reference to the term pneumonia, in the case of COVID-19, is neither scientifically or clinically feasible. The most correct would be to call this process viral or virus-associated lung damage. This term will allow you to set priorities in the choice of tactics leading the patient. That is, viral lesion (not pneumonia!) will induce the practical doctor to analyze the situation requiring prescription in the presence of indications of anti-inflammatory (monoclonal antibodies, glucocorticosteroids) and anticoagulation therapy, and will avoid unnecessary in the overwhelming number of antimicrobial prescription situations.
 AIM: Formulate criteria for prescribing antibacterial therapy in patients with COVID-19.
 MATERIALS AND METHODS: The study is based on a review and analysis of the literature on new coronavirus infection, drawing conclusions and recommendations.
 RESULTS: In actual Russian practice, the level of use of antibiotics remains extremely high, reaching 7080%.
 CONCLUSION: The prescription of antibacterial therapy in patients with COVID-19 is justified only if there are convincing signs of bacterial infection the appearance of purulent sputum, increased procalcitonin of blood more than 0,250.5 ng/ml, an increase in blood white count of more than 10 thousand/mcl with an increase in the number band neutrophils more than 10%.

Intact Type I Interferon Receptor Signaling Prevents Hepatocellular Necrosis but Not Encephalitis in a Dose-Dependent Manner in Rift Valley Fever Virus Infected Mice.

Rift Valley fever (RVF) is a zoonotic and emerging disease, caused by the RVF virus (RVFV). In ruminants, it leads to “abortion storms” and enhanced mortality rates in young animals, whereas in humans it can cause symptoms like severe hemorrhagic fever or encephalitis. The role of the innate and adaptive immune response in disease initiation and progression is still poorly defined. The present study used the attenuated RVFV strain clone 13 to investigate viral spread, tissue tropism, and histopathological lesions after intranasal infection in C57BL/6 wild type (WT) and type I interferon (IFN-I) receptor I knockout (IFNAR−/−) mice. In WT mice, 104 PFU RVFV (high dose) resulted in a fatal encephalitis, but no hepatitis 7–11 days post infection (dpi), whereas 103 PFU RVFV (low dose) did not cause clinical disease or significant histopathological lesions in liver and the central nervous system (CNS). In contrast, IFNAR−/− mice infected with 103 PFU RVFV developed hepatocellular necrosis resulting in death at 2–5 dpi and lacked encephalitis. These results show that IFNAR signaling prevents systemic spread of the attenuated RVFV strain clone 13, but not the dissemination to the CNS and subsequent fatal disease. Consequently, neurotropic viruses may be able to evade antiviral IFN-I signaling pathways by using the transneuronal instead of the hematogenous route.

SARS-CoV-2 Variant-Specific Infectivity and Immune Profiles Are Detectable in a Humanized Lung Mouse Model.

Small animal models that accurately model pathogenesis of SARS-CoV-2 variants are required for ongoing research efforts. We modified our human immune system mouse model to support replication of SARS-CoV-2 by implantation of human lung tissue into the mice to create TKO-BLT-Lung (L) mice and compared infection with two different variants in a humanized lung model. Infection of TKO-BLT-L mice with SARS-CoV-2 recapitulated the higher infectivity of the B.1.1.7 variant with more animals becoming infected and higher sustained viral loads compared to mice challenged with an early B lineage (614D) virus. Viral lesions were observed in lung organoids but no differences were detected between the viral variants as expected. Partially overlapping but distinct immune profiles were also observed between the variants with a greater Th1 profile in VIDO-01 and greater Th2 profile in B.1.1.7 infection. Overall, the TKO-BLT-L mouse supported SARS-CoV-2 infection, recapitulated key known similarities and differences in infectivity and pathogenesis as well as revealing previously unreported differences in immune responses between the two viral variants. Thus, the TKO-BLT-L model may serve as a useful animal model to study the immunopathobiology of newly emerging variants in the context of genuine human lung tissue and immune cells.

HISTOPATHOLOGICAL STUDY OF NON-NEOPLASTIC LESIONS OF SKIN

Objectives: The objectives of the study were as follows: (1) To find the prevalence of various non-neoplastic skin lesions in our tertiary care hospital. (2) To study the age- and sex-wise distribution of non-neoplastic skin lesions. (3) To compare the results of the present study with other studies. Methods: The present study comprised total 200 punch biopsy specimens of diagnosed cases of non-neoplastic lesions of skin, detailed clinical data, age, sex, and sites of skin lesion of patients which were included in the study. Specimens received were fixed in 10% formalin. Biopsy bits were submitted as whole and processed in automated tissue processor for routine paraffin embedding. Results: A total of 200 lesions were analyzed. Maximum cases were in the age group of 21–30 years followed by 31–40 years age. Fifty-five (27.5%) cases were of non-infectious erythematous, papular, and squamous diseases followed by 54 (27%) cases of vesiculobullous and vesiculopustular diseases, 37 (18.5%) cases of bacterial diseases, 20 (10%) cases of fungal diseases, and 34 (17%) cases of vascular lesions, connective tissue disorders, non-infectious granulomas, perforating disorders, etc. Conclusion: Skin lesions were common in males than in females with male: female ratio of 1.38:1. Younger age group was more commonly affected. Non-infectious erythematous, papular, and squamous lesions were most common with psoriasis being the most common followed by non-infectious vesiculobullous and vesiculopustular lesions with pemphigus vulgaris being the most common, followed by infective lesions consisting of bacterial, fungal, and viral lesions. Other lesions consisted of vascular skin lesions, connective tissue disorders non-infectious granulomas, perforating disorders, etc.

RNA G-quadruplex formed in SARS-CoV-2 used for COVID-19 treatment in animal models

The ongoing COVID-19 pandemic has continued to affect millions of lives worldwide, leading to the urgent need for novel therapeutic strategies. G-quadruplexes (G4s) have been demonstrated to regulate life cycle of multiple viruses. Here, we identify several highly conservative and stable G4s in SARS-CoV-2 and clarify their dual-function of inhibition of the viral replication and translation processes. Furthermore, the cationic porphyrin compound 5,10,15,20-tetrakis-(N-methyl-4-pyridyl)porphine (TMPyP4) targeting SARS-CoV-2 G4s shows excellent antiviral activity, while its N-methyl-2-pyridyl positional isomer TMPyP2 with low affinity for G4 has no effects on SARS-CoV-2 infection, suggesting that the antiviral activity of TMPyP4 attributes to targeting SARS-CoV-2 G4s. In the Syrian hamster and transgenic mouse models of SARS-CoV-2 infection, administration of TMPyP4 at nontoxic doses significantly suppresses SARS-CoV-2 infection, resulting in reduced viral loads and lung lesions. Worth to note, the anti-COVID-19 activity of TMPyP4 is more potent than remdesivir evidenced by both in vitro and in vivo studies. Our findings highlight SARS-CoV-2 G4s as a novel druggable target and the compelling potential of TMPyP4 for COVID-19 therapy. Different from the existing anti-SARS-CoV-2 therapeutic strategies, our work provides another alternative therapeutic tactic for SARS-CoV-2 infection focusing on targeting the secondary structures within SARS-CoV-2 genome, and would open a new avenue for design and synthesis of drug candidates with high selectivity toward the new targets.

The study of antigen carrying and lesions observed in pigs that survived post African swine fever virus infection.

African swine fever (ASF) is a dangerous infectious disease of domestic pigs and wild boar caused by African swine fever virus (ASFV). In Vietnam, the ASF epidemic is gradually turning into an endemic status with several recovered pigs post infection, but there were not many studies evaluating the role of these pigs in the epidemiological context in Vietnam. The aim of this study was to evaluate the viral antigen distribution and lesions in recovered pigs post ASFV infection. Ten pigs recovered from ASF at 6 weeks of age were monitored and assessed for anti-ASFV antibodies and viremia until slaughter. The five major organs (lung, liver, spleen, kidney, and lymph nodes) of these pigs were evaluated for microscopic lesions and viral antigen distribution. Anti-ASFV antibody was consistently observed to be high (S/P% ≥ 80) until slaughter, while viremia levels were very high (7 log10 copies/mL) at 6 weeks of age and gradually decreased to undetectable levels at 12 weeks of age (6th week post-infection). At slaughter, the ASFV-associated lesions in the organs of these pigs were mild and nonspecific. Seven out of ten pigs recovering from ASF still carried the virus in surveyed organ tissues, although not in the serum. These findings suggest that ASF-recovered pigs may be potential carriers of the virus, contributing to the increased complexity in the current endemic status in Vietnam.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11250-022-03229-0.