N95 respirator hybrid decontamination method using Ultraviolet Germicidal Irradiation (UVGI) coupled with Microwave-Generated Steam (MGS).

The Coronavirus Disease 2019 (COVID-19) pandemic has induced a critical supply of personal protective equipment (PPE) especially N95 respirators. Utilizing respirator decontamination procedures to reduce the pathogen load of a contaminated N95 respirator can be a viable solution for reuse purposes. In this study, the efficiency of a novel hybrid respirator decontamination method of ultraviolet germicidal irradiation (UVGI) which utilizes ultraviolet-C (UV-C) rays coupled with microwave-generated steam (MGS) against feline coronavirus (FCoV) was evaluated. The contaminated 3M 1860 respirator pieces were treated with three treatments (UVGI-only, MGS-only, and Hybrid-UVGI + MGS) with variable time. The virucidal activity was evaluated using the TCID50 method. The comparison of decontamination efficiency of the treatments indicated that the hybrid method achieved at least a pathogen log reduction of 4 logs, faster than MGS and UVGI. These data recommend that the proposed hybrid decontamination system is more effective comparatively in achieving pathogen log reduction of 4 logs.

Seroprevalence of dengue and chikungunya viruses among urban refugees in Klang Valley, Malaysia.

BACKGROUND: Mosquito-borne diseases pose a significant global public health threat, with Malaysia's Klang Valley experiencing numerous outbreaks in densely populated urban areas. METHODS: This study aimed to estimate the seroprevalence of anti-dengue and anti-chikungunya antibodies among urban refugees in the Klang Valley, Malaysia, and identify associated risk factors. RESULTS: High seroprevalence of anti-dengue immunoglobulin G (IgG) and IgM (60.0% [confidence interval {CI} 55.39 to 64.48] and 9.2% [CI 6.77 to 12.25], respectively) were observed among refugees >18 years of age (χ22=11.720, p=0.003), Kachin ethnicity (χ28=72.253, p<0.001), without formal education (χ21=3.856, p=0.050), homes near waste disposal sites (χ21=10.378, p=0.001) and refugees who have experienced flooding (χ21=5.460, p=0.019). Meanwhile, the overall seroprevalence of anti-chikungunya IgG and IgM was 9.7% (CI 7.15 to 12.73) and 10.8% (CI 8.09 to 13.93), respectively, with ages 12-18 years (χ22=6.075, p=0.048), Rohingya ethnicity (χ28=31.631, p<0.001) and homes close to waste disposal sites (χ21=3.912, p=0.048) being significant risk factors. Results showed a link to poor environmental living conditions, with an increase in the vector population with higher availability of breeding sites and thus exposure to dengue and chikungunya virus. CONCLUSIONS: Health education among the community is the key to disease prevention, as there are no specific antiviral drugs for treatment and limited vaccine availability.

From defense to offense: Modulating toll-like receptors to combat arbovirus infections.

Arboviruses are a significant threat to global public health, with outbreaks occurring worldwide. Toll-like receptors (TLRs) play a crucial role in the innate immune response against these viruses by recognizing pathogen-associated molecular patterns and initiating an inflammatory response. Significantly, TLRs commonly implicated in the immune response against viral infections include TLR2, TLR4, TLR6, TLR3, TLR7, and TLR8; limiting or allowing them to replicate and spread within the host. Modulating TLRs has emerged as a promising approach to combat arbovirus infections. This review summarizes recent advances in TLR modulation as a therapeutic target in arbovirus infections. Studies have shown that the activation of TLRs can enhance the immune response against arbovirus infections, leading to increased viral clearance and protection against disease. Conversely, inhibition of TLRs can reduce the excessive inflammation and tissue damage associated with arbovirus infection. Modulating TLRs represents a potential therapeutic strategy to combat arbovirus infections.

Gene expression profiling of host lipid metabolism in SARS-CoV-2 infected patients: a systematic review and integrated bioinformatics analysis.

BACKGROUND: The Coronavirus disease 2019 (COVID-19) pandemic occurred due to the dispersion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Severe symptoms can be observed in COVID-19 patients with lipid-related comorbidities such as obesity and diabetes. Yet, the extensive molecular mechanisms of how SARS-CoV-2 causes dysregulation of lipid metabolism remain unknown. METHODS: Here, an advanced search of articles was conducted using PubMed, Scopus, EBSCOhost, and Web of Science databases using terms from Medical Subject Heading (MeSH) like SARS-CoV-2, lipid metabolism and transcriptomic as the keywords. From 428 retrieved studies, only clinical studies using next-generation sequencing as a gene expression method in COVID-19 patients were accepted. Study design, study population, sample type, the method for gene expression and differentially expressed genes (DEGs) were extracted from the five included studies. The DEGs obtained from the studies were pooled and analyzed using the bioinformatics software package, DAVID, to determine the enriched pathways. The DEGs involved in lipid metabolic pathways were selected and further analyzed using STRING and Cytoscape through visualization by protein-protein interaction (PPI) network complex. RESULTS: The analysis identified nine remarkable clusters from the PPI complex, where cluster 1 showed the highest molecular interaction score. Three potential candidate genes (PPARG, IFITM3 and APOBEC3G) were pointed out from the integrated bioinformatics analysis in this systematic review and were chosen due to their significant role in regulating lipid metabolism. These candidate genes were significantly involved in enriched lipid metabolic pathways, mainly in regulating lipid homeostasis affecting the pathogenicity of SARS-CoV-2, specifically in mechanisms of viral entry and viral replication in COVID-19 patients. CONCLUSIONS: Taken together, our findings in this systematic review highlight the affected lipid-metabolic pathways along with the affected genes upon SARS-CoV-2 invasion, which could be a potential target for new therapeutic strategies study in the future.

Antiviral Activities of Streptomyces KSF 103 Methanolic Extracts against Dengue Virus Type-2.

Dengue has long been a serious health burden to the global community, especially for those living in the tropics. Despite the availability of vaccines, effective treatment for the infection is still needed and currently remains absent. In the present study, the antiviral properties of the Streptomyces sp. KSF 103 methanolic extract (Streptomyces KSF 103 ME), which consists of a number of potential antiviral compounds, were investigated against dengue virus serotype 2 (DENV-2). The effects of this extract against DENV-2 replication were determined using the quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Findings from the study suggested that the Streptomyces KSF 103 ME showed maximum inhibitory properties toward the virus during the virus entry stage at concentrations of more than 12.5 µg/mL. Minimal antiviral activities were observed at other virus replication stages; adsorption (42% reduction at 50 µg/mL), post-adsorption (67.6% reduction at 50 µg/mL), prophylactic treatment (68.4% and 87.7% reductions at 50 µg/mL and 25 µg/mL, respectively), and direct virucidal assay (48% and 56.8% reductions at 50 µg/mL and 25 µg/mL, respectively). The Streptomyces KSF 103 ME inhibited dengue virus replication with a 50% inhibitory concentration (IC50) value of 20.3 µg/mL and an International System of Units (SI) value of 38.9. The Streptomyces KSF 103 ME showed potent antiviral properties against dengue virus (DENV) during the entry stage. Further studies will be needed to deduce the antiviral mechanisms of the Streptomyces KSF 103 ME against DENV.

Protein Profiling of Aedes aegypti Treated with Streptomyces sp. KSF103 Ethyl Acetate Extract Reveals Potential Insecticidal Targets and Metabolic Pathways.

The insecticidal activity of Streptomyces sp. KSF103 ethyl acetate (EA) extract against mosquitoes is known; however, the underlying mechanism behind this activity remains elusive. In this study, liquid chromatography with tandem mass spectrometry (LC-MS/MS) was employed to investigate changes in the protein profile of Aedes aegypti larvae and adults treated with lethal concentrations of 50 (LC50) EA extract. By comparing the treated and untreated mosquitoes, this study aimed to identify proteins or pathways that exhibit alterations, potentially serving as targets for future insecticide development. Treatment with a lethal concentration of EA extract upregulated 15 proteins in larvae, while in adults, 16 proteins were upregulated, and two proteins were downregulated. These proteins were associated with metabolism, protein regulation/degradation, energy production, cellular organization and structure, enzyme activity, and catalysis, as well as calcium ion transport and homeostasis. Notably, ATP synthase, fructose-bisphosphate aldolase (FBA), and ATP citrate synthase were significantly expressed in both groups. Gene ontology analysis indicated a focus on energy metabolic processes. Molecular docking revealed a strong interaction between dodemorph, selagine (compounds from the EA extract), and FBA, suggesting FBA as a potential protein target for insecticide development. Further studies such as Western blot and transcriptomic analyses are warranted to validate the findings.

COVID-19 Therapeutic Potential of Natural Products.

Despite the fact that coronavirus disease 2019 (COVID-19) treatment and management are now considerably regulated, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still one of the leading causes of death in 2022. The availability of COVID-19 vaccines, FDA-approved antivirals, and monoclonal antibodies in low-income countries still poses an issue to be addressed. Natural products, particularly traditional Chinese medicines (TCMs) and medicinal plant extracts (or their active component), have challenged the dominance of drug repurposing and synthetic compound libraries in COVID-19 therapeutics. Their abundant resources and excellent antiviral performance make natural products a relatively cheap and readily available alternative for COVID-19 therapeutics. Here, we deliberately review the anti-SARS-CoV-2 mechanisms of the natural products, their potency (pharmacological profiles), and application strategies for COVID-19 intervention. In light of their advantages, this review is intended to acknowledge the potential of natural products as COVID-19 therapeutic candidates.

Avian Influenza Virus Tropism in Humans.

An influenza pandemic happens when a novel influenza A virus is able to infect and transmit efficiently to a new, distinct host species. Although the exact timing of pandemics is uncertain, it is known that both viral and host factors play a role in their emergence. Species-specific interactions between the virus and the host cell determine the virus tropism, including binding and entering cells, replicating the viral RNA genome within the host cell nucleus, assembling, maturing and releasing the virus to neighboring cells, tissues or organs before transmitting it between individuals. The influenza A virus has a vast and antigenically varied reservoir. In wild aquatic birds, the infection is typically asymptomatic. Avian influenza virus (AIV) can cross into new species, and occasionally it can acquire the ability to transmit from human to human. A pandemic might occur if a new influenza virus acquires enough adaptive mutations to maintain transmission between people. This review highlights the key determinants AIV must achieve to initiate a human pandemic and describes how AIV mutates to establish tropism and stable human adaptation. Understanding the tropism of AIV may be crucial in preventing virus transmission in humans and may help the design of vaccines, antivirals and therapeutic agents against the virus.

Insecticidal activities of Streptomyces sp. KSF103 ethyl acetate extract against medically important mosquitoes and non-target organisms.

A potentially novel actinobacterium isolated from forest soil, Streptomyces sp. KSF103 was evaluated for its insecticidal effect against several mosquito species namely Aedes aegypti, Aedes albopictus, Anopheles cracens and Culex quinquefasciatus. Mosquito larvae and adults were exposed to various concentrations of the ethyl acetate (EA) extract for 24 h. Considerable mortality was evident after the EA extract treatment for all four important vector mosquitoes. Larvicidal activity of the EA extract resulted in LC50 at 0.045 mg/mL and LC90 at 0.080 mg/mL for Ae. aegypti; LC50 at 0.060 mg/mL and LC90 at 0.247 mg/mL for Ae. albopictus; LC50 at 2.141 mg/mL and LC90 at 6.345 mg/mL for An. cracens; and LC50 at 0.272 mg/mL and LC90 at 0.980 mg/mL for Cx. quinquefasciatus. In adulticidal tests, the EA extract was the most toxic to Ae. albopictus adults (LD50 = 2.445 mg/mL; LD90 = 20.004 mg/mL), followed by An. cracens (LD50 = 5.121 mg/mL; LD90 = 147.854 mg/mL) and then Ae. aegypti (LD50 = 28.873 mg/mL; LD90 = 274.823 mg/mL). Additionally, the EA extract exhibited ovicidal activity against Ae. aegypti (LC50 = 0.715 mg/mL; LC90 = 6.956 mg/mL), Ae. albopictus (LC50 = 0.715 mg/mL; LC90 = 6.956 mg/mL), and An. cracens (LC50 = 0.715 mg/mL; LC90 = 6.956 mg/mL), evaluated up to 168 h post-treatment. It displayed no toxicity on the freshwater microalga Chlorella sp. Beijerinck UMACC 313, marine microalga Chlorella sp. Beijerinck UMACC 258 and the ant Odontoponera denticulata. In conclusion, the EA extract showed promising larvicidal, adulticidal and ovicidal activity against Ae. aegypti, Ae. albopictus, An. cracens, and Cx. quinquefasciatus (larvae only). The results suggest that the EA extract of Streptomyces sp. KSF103 has the potential to be used as an environmental-friendly approach in mosquito control. The current study would serve as an initial step toward complementing microbe-based bioinsecticides for synthetic insecticides against medically important mosquitoes.

Knowledge of SARS-CoV-2 Epitopes and Population HLA Types Is Important in the Design of COVID-19 Vaccines.

The COVID-19 pandemic has caused extensive loss of lives and economic hardship. In response, infectious disease experts and vaccine developers promptly responded by bringing forth candidate vaccines, some of which have been listed in the World Health Organization's Emergency Use Listing. Notwithstanding the diverse worldwide population genetics, the vaccines thus far developed are generic in nature for use worldwide. Differences in the human leukocyte antigen (HLA) in different populations, variation of the T cell epitopes, and the propensity of SARS-CoV-2 genetic mutations left room for improvement of the vaccines. Here, we discussed the implications of COVID-19 vaccination and SARS-CoV-2 infection by taking into consideration SARS-CoV-2 mutations, T cell epitopes, risk factors, and current platforms of candidate vaccines based on the HLA types that are commonly present in Peninsular Malaysia Chinese, Indian, and Malay populations. The HLA types associated with protection against and susceptibility to severe SARS-CoV-2 infection were identified based on reported case-control and cohort studies. The relevance of including the non-spike SARS-CoV-2 proteins in the future COVID-19 vaccines is also highlighted. This review is meant to trigger researchers to acknowledge the importance of investigating the possible relationships between the HLA haplotype and the SARS-CoV-2 strains circulating in different populations.

Chitosan and its derivatives as polymeric anti-viral therapeutics and potential anti-SARS-CoV-2 nanomedicine.

The coronavirus pandemic, COVID-19 has a global impact on the lives and livelihoods of people. It is characterized by a widespread infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), where infected patients may develop serious medical complications or even face death. Development of therapeutic is essential to reduce the morbidity and mortality of infected patients. Chitosan is a versatile biomaterial in nanomedicine and exhibits anti-microbial, anti-cancer and immunomodulatory properties. This review highlights the progress in chitosan design and application pertaining to the anti-viral effects of chitosan and chitosan derivatives (hydroxypropyl trimethylammonium, sulfate, carboxymethyl, bromine, sialylglycopolymer, peptide and phosphonium conjugates) as a function of molecular weight, degree of deacetylation, type of substituents and their degree and site of substitution. The physicochemical attributes of these polymeric therapeutics are identified against the possibility of processing them into nanomedicine which can confer a higher level of anti-viral efficacy. The designs of chitosan for the purpose of targeting SARS-CoV-2, as well as the ever-evolving strains of viruses with a broad spectrum anti-viral activity to meet pandemic preparedness at the early stages of outbreak are discussed.

Intracellular translocation of HMGB1 is important for Zika virus replication in Huh7 cells.

Neonatal microcephaly and adult Guillain-Barré syndrome are severe complications of Zika virus (ZIKV) infection. The robustly induced inflammatory cytokine expressions in ZIKV-infected patients may constitute a hallmark for severe disease. In the present study, the potential role of high mobility group box 1 protein (HMGB1) in ZIKV infection was investigated. HMGB1 protein expression was determined by the enzyme-linked immunosorbent assay (ELISA) and immunoblot assay. HMGB1's role in ZIKV infection was also explored using treatment with dexamethasone, an immunomodulatory drug, and HMGB1-knockdown (shHMGB1) Huh7 cells. Results showed that the Huh7 cells were highly susceptible to ZIKV infection. The infection was found to induce HMGB1 nuclear-to-cytoplasmic translocation, resulting in a > 99% increase in the cytosolic HMGB1 expression at 72-h post-infection (h.p.i). The extracellular HMGB1 level was elevated in a time- and multiplicity of infection (MOI)-dependent manner. Treatment of the ZIKV-infected cells with dexamethasone (150 µM) reduced HMGB1 extracellular release in a dose-dependent manner, with a maximum reduction of 71 ± 5.84% (P < 0.01). The treatment also reduced virus titers by over 83 ± 0.50% (P < 0.01). The antiviral effects, however, were not observed in the dexamethasone-treated shHMGB1 cells. These results suggest that translocation of HMGB1 occurred during ZIKV infection and inhibition of the translocation by dexamethasone coincided with a reduction in ZIKV replication. These findings highlight the potential of targeting the localization of HMGB1 in affecting ZIKV infection.

The effectiveness of various gargle formulations and salt water against SARS-CoV-2.

The COVID-19 is difficult to contain due to its high transmissibility rate and a long incubation period of 5 to 14 days. Moreover, more than half of the infected patients were young and asymptomatic. Virus transmission through asymptomatic patients is a major challenge to disease containment. Due to limited treatment options, preventive measures play major role in controlling the disease spread. Gargling with antiseptic formulation may have potential role in eliminating the virus in the throat. Four commercially available mouthwash/gargle formulations were tested for virucidal activity against SARS-CoV-2 in both clean (0.3 g/l BSA) and dirty (0.3 g/l BSA + 3 mL/L human erythrocytes) conditions at time points 30 and 60 s. The virus was isolated and propagated in Vero E6 cells. The cytotoxicity of the products to the Vero E6 was evaluated by kill time assay based on the European Standard EN14476:2013/FprA1:2015 protocol. Virus titres were calculated as 50% tissue culture infectious dose (TCID50/mL) using the Spearman-Karber method. A reduction in virus titer of 4 log10 corresponds to an inactivation of ≥ 99.99%. Formulations with cetylperidinium chloride, chlorhexidine and hexitidine achieved > 4 log10 reduction in viral titres when exposed within 30 s under both clean and dirty conditions. Thymol formulations achieved only 0.5 log10 reduction in viral titres. In addition, salt water was not proven effective. Gargle formulations with cetylperidinium chloride, chlorhexidine and hexetidine have great potential in reducing SAR-CoV-2 at the source of entry into the body, thus minimizing risk of transmission of COVID-19.

Antiviral activity of silymarin and baicalein against dengue virus.

Dengue is an arthropod-borne viral disease that has become endemic and a global threat in many countries with no effective antiviral drug available currently. This study showed that flavonoids: silymarin and baicalein could inhibit the dengue virus in vitro and were well tolerated in Vero cells with a half-maximum cytotoxic concentration (CC50) of 749.70 µg/mL and 271.03 µg/mL, respectively. Silymarin and baicalein exerted virucidal effects against DENV-3, with a selective index (SI) of 10.87 and 21.34, respectively. Baicalein showed a better inhibition of intracellular DENV-3 progeny with a SI of 7.82 compared to silymarin. Baicalein effectively blocked DENV-3 attachment (95.59%) to the Vero cells, while silymarin prevented the viral entry (72.46%) into the cells, thus reducing viral infectivity. Both flavonoids showed promising antiviral activity against all four dengue serotypes. The in silico molecular docking showed that silymarin could bind to the viral envelope (E) protein with a binding affinity of - 8.5 kcal/mol and form hydrogen bonds with the amino acids GLN120, TRP229, ASN89, and THR223 of the E protein. Overall, this study showed that silymarin and baicalein exhibited potential anti-DENV activity and could serve as promising antiviral agents for further development against dengue infection.

Baicalein and Baicalin Inhibit SARS-CoV-2 RNA-Dependent-RNA Polymerase.

Coronavirus Disease 2019 (COVID-19) is a deadly emerging infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Because SARS-CoV-2 is easily transmitted through the air and has a relatively long incubation time, COVID-19 has rapidly developed into a global pandemic. As there are no antiviral agents for the prevention and treatment of this severe pathogen except for remdesivir, development of antiviral therapies to treat infected individuals remains highly urgent. Here, we showed that baicalein and baicalin exhibited significant antiviral activity against SARS-CoV-2, the causative agent of COVID-19 through in vitro studies. Our data through cell-based and biochemical studies showed that both compounds act as SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) inhibitors directly and inhibit the activity of the SARS-CoV-2 RdRp, but baicalein was more potent. We also showed specific binding of baicalein to the SARS-CoV-2 RdRp, making it a potential candidate for further studies towards therapeutic development for COVID-19 as a selective non-nucleoside polymerase inhibitor.

In vitro virucidal activity of povidone iodine gargle and mouthwash against SARS-CoV-2: implications for dental practice.

Introduction Virus particles in respiratory droplets and aerosols generated during medical/dental procedures are a potential source of SARS-CoV-2 cross infection. In the dental setting, oral decontamination could be an important adjunct to personal protective equipment and is recommended by a number of national COVID-19 guidance documents for dental settings.Aim To assess the in vitrovirucidal activity of an oral povidone iodine (PVP-I) product against SARS-CoV-2.Material and methods BETADINE gargle and mouthwash (1% PVP-I) was tested against SARS-CoV-2 virus under both clean and dirty conditions using a suspension assay based on EN14476 methodology. Virucidal activity of the product, undiluted and at 1:2 dilution, was tested at contact times of 15, 30 and 60 seconds. Viral titres were calculated using the Spearman-Kärber method and reported as median tissue culture infectious dose (TCID50/ml).Results The undiluted product achieved >5 log10 reduction in viral titres compared to the control at 15, 30 and 60 seconds under both clean and dirty conditions. At a twofold dilution (0.5% PVP-I), the test product demonstrated >4 log10 kill at 15 seconds and >5 log10 kill at 30 and 60 seconds in both clean and dirty conditions.Conclusion PVP-I gargle and mouthwash product, undiluted and at 1:2 dilution, demonstrated potent and rapid virucidal activity (≥4 log10 reduction of viral titre) in 15 seconds against SARS-CoV-2 in vitro. The PVP-I gargle and mouthwash product is widely available and could be readily integrated into infection control measures during dental treatment including pre-procedural oral decontamination.

Nucleoside Analogs with Selective Antiviral Activity against Dengue Fever and Japanese Encephalitis Viruses.

Dengue virus (DENV) and Japanese encephalitis virus (JEV) are important arthropod-borne viruses from the Flaviviridae family. DENV is a global public health problem with significant social and economic impacts, especially in tropical and subtropical areas. JEV is a neurotropic arbovirus endemic to east and southeast Asia. There are no U.S. FDA-approved antiviral drugs available to treat or to prevent DENV and JEV infections, leaving nearly one-third of the world's population at risk for infection. Therefore, it is crucial to discover potent antiviral agents against these viruses. Nucleoside analogs, as a class, are widely used for the treatment of viral infections. In this study, we discovered nucleoside analogs that possess potent and selective anti-JEV and anti-DENV activities across all serotypes in cell-based assay systems. Both viruses were susceptible to sugar-substituted 2'-C-methyl analogs with either cytosine or 7-deaza-7-fluoro-adenine nucleobases. Mouse studies confirmed the anti-DENV activity of these nucleoside analogs. Molecular models were assembled for DENV serotype 2 (DENV-2) and JEV RNA-dependent RNA polymerase replication complexes bound to nucleotide inhibitors. These models show similarities between JEV and DENV-2, which recognize the same nucleotide inhibitors. Collectively, our findings provide promising compounds and a structural rationale for the development of direct-acting antiviral agents with dual activity against JEV and DENV infections.

Corrigendum to "Acute Toxicity and Gastroprotective Role of M. pruriens in Ethanol-Induced Gastric Mucosal Injuries in Rats".

[This corrects the article DOI: 10.1155/2013/974185.].

Corrigendum to "Gastroprotective Activity of Polygonum chinense Aqueous Leaf Extract on Ethanol-Induced Hemorrhagic Mucosal Lesions in Rats".

[This corrects the article DOI: 10.1155/2012/404012.].