Anti-herpes Simplex Research Articles

Surface different charge ligands for modulating selenium nanoparticles formation and activating the interaction with proteins for effective anti-Herpes simplex virus l infection

Selenium-based nanoparticles exhibit antiviral activity by directly modulating immune function. Despite recent promising developments in utilizing selenium nanoparticles (Se NPs) against viral infections, the impact of surface ligand charge on the conformation and interaction with viral proteins, as well as the effectiveness of Se NPs in anti-Herpes simplex virus 1 (HSV-1) infection remains unexplored. In this study, three types of selenium nanoparticles (CTAB-Se, PVP-Se, SDS-Se) with distinct surface charges were synthesized by modifying the surface ligands. We found that apart from differences in surface charge, the size, morphology, and crystal structure of the three types of Se NPs were similar. Notably, although the lipophilicity and cellular uptake of SDS-Se with a negative charge were lower compared to positively charged CTAB-Se and neutrally charged PVP-Se, SDS-Se exhibited the strongest protein binding force during interaction with HSV-1. Consequently, SDS-Se demonstrated the most potent anti-HSV-1 activity and safeguarded normal cells from damage. The mechanistic investigation further revealed that SDS-Se NPs effectively inhibited the proliferation and assembly of HSV-1 by powerfully suppressing the key genes and proteins of HSV-1 at various stages of viral development. Hence, this study highlights the significant role of surface ligand engineering in the antiviral activity of Se NPs, presenting a viable approach for synthesizing Se NPs with tailored antiviral properties by modulating surface charge. This method holds promise for advancing research on the antiviral capabilities of Se NPs.

Clinicopathological Study of Herpes Simplex Esophagitis in a Tertiary Centre in India

Introduction and objectives: Herpes Simplex Virus (HSV) is a common viral pathogen, known to cause symptomatic disease in the immunocompromised hosts; however, it may occur in healthy individuals as well. Among the varied manifestations of the disease, involving skin, central nervous system and gastrointestinal systems, HSV esophagitis is a less studied entity from the Indian perspective. The aim of the study is to compare clinical, histologic and serologic data of HSV esophagitis patients. Materials and methods: 27 cases, proved to have HSV esophagitis on endoscopic biopsy were included, and the pertinent clinical and serologic characteristics were studied. Results: We found a male preponderance (p<0.01), which has been a well-established risk factor. Other risk factors are retroviral coinfection, Type 2 Diabetes Mellitus, immunosuppression, chemoradiation etc. among others. Eleven patients had retroviral coinfection, with CD4 counts of > 200/μL in all. Anti HSV 1 IgM antibody was most commonly detected on serology. HSV esophagitis affects immunocompromised patients more often than immunocompetent ones. Odynophagia and dysphagia are the most common symptoms. Histological evaluation for the characteristic inclusions helps in early diagnosis. The novelty of this study rests on the clinicopathological and serologic correlation, for a better understanding of the disease process, to prompt future large scale studies on the same. Conclusion: Herpes simplex esophagitis is most seen in immunocompromised patients. Apart from retroviral illness, other risk factors include diabetes mellitus, patients undergoing chemotherapy and other malignancy. CD4 counts in our series was >200/μL, in contrast to the cutoff of <200/μL described in literature.

Nuciferol C, a new sesquineolignan dimer from Cocos nucifera L.: bioactivity and theoretical investigation.

Nuciferol C (NC), an undescribed dimer of nuciferol B (NB), was isolated from the endocarp of Cocos nucifera L. The planar structure of NC was determined using 1D- and 2D-NMR spectroscopy as well as high resolution MS spectrometry. The absolute configuration was concluded based on analysis of NOESY spectra. NC showed cytotoxic activity against colon cancer cells (CaCo-2) with an IC50 value of 76 μM, and significantly decreased the expression of human epidermal growth factor receptor (EGFR) and tumor necrosis factor alpha (TNF-α) in CaCo-2 as compared with untreated cells by 39% and 33%, respectively (p < 0.05). In addition, NC exhibited anti-herpes simplex virus (HSV-I) activity with an IC50 value of 23 μM. In silico study of NC was implemented at three levels: density functional theory (DFT) was used to study its electronic properties, molecular mechanics was used to estimate the docking results, and finally, molecular dynamic simulation was used to study the behavior and stability of NC inside the active site of the target protein of HSV-1.

Antibody immune responses and causal relationships in four immune skin diseases: Evidence from Mendelian randomization and Bayesian Weighting (Antibody Responses in Skin Diseases: MR & Bayesian).

Recent studies increasingly suggest that microbial infections and the immune responses they elicit play significant roles in the pathogenesis of chronic inflammatory skin diseases. This study uses Mendelian randomization (MR) and Bayesian weighted Mendelian randomization (BWMR) to explore the causal relationships between immune antibody responses and four common skin diseases: psoriasis, atopic dermatitis (AD), rosacea, and vitiligo. We utilized summary statistics from genome-wide association studies (GWAS) for antibody responses to 13 infectious pathogens and four skin diseases. Single nucleotide polymorphisms (SNPs) were selected as instrumental variables (IVs) to assess causal relationships using multiple MR methods, including inverse variance weighted (IVW), MR Egger, and weighted median. BWMR was also employed to confirm findings and address potential pleiotropy. The IVW analysis identified significant associations between specific antibody responses and the skin diseases studied. Key findings include protective associations of anti-Epstein-Barr virus (EBV) IgG seropositivity and Helicobacter pylori UREA antibody levels with psoriasis and AD. anti-chlamydia trachomatis IgG seropositivity, anti-polyomavirus 2 IgG seropositivity, and varicella zoster virus glycoprotein E and I antibody levels were negatively associated with rosacea, while EBV Elevated levels of the early antigen (EA-D) antibody levels and HHV-6 IE1B antibody levels were positively associated with rosacea. H. pylori Catalase antibody levels were protectively associated with vitiligo, whereas anti-herpes simplex virus 2 (HSV-2) IgG seropositivity was positively associated with vitiligo. The BWMR analysis confirmed these associations. This study underscores the significant role of H. pylori and other pathogens in these skin diseases, suggesting both protective and exacerbating effects depending on the specific condition. Understanding these pathogen-immune interactions can lead to the development of more effective, personalized treatments and preventative strategies, ultimately improving patient outcomes and quality of life.

Anti-Herpes Simplex Virus and Anti-Inflammatory Activities of the Melittin Peptides Derived from Apis mellifera and Apis florea Venom.

Herpes simplex virus (HSV) is known to cause cold sores and various diseases in humans. Importantly, HSV infection can develop latent and recurrent infections, and it is also known to cause inflammation. These infections are difficult to control, and effective treatment of the disease remains a challenge. Thus, the search for new antiviral and anti-inflammatory agents is a necessity. Melittin is a major peptide that is present in the venom of the honeybee. It possesses a number of pharmacological properties. In this study, the effects of the melittin peptides from A. mellifera (MEL-AM) and A. florea (MEL-AF) against HSV-1 and HSV-2 were evaluated at different stages during the viral multiplication cycle in an attempt to define the mode of antiviral action using plaque reduction and virucidal assays. The results revealed a new finding that melittin at 5 µg/mL demonstrated the highest inhibitory effect on HSV through the direct inactivation of viral particles, and MEL-AF displayed a greater virucidal activity. Moreover, melittin was also observed to interfere with the process of HSV attachment to the host cells. MEL-AM exhibited anti-HSV-1 and anti-HSV-2 effects with EC50 values of 4.90 ± 0.15 and 4.39 ± 0.20 µg/mL, while MEL-AF demonstrated EC50 values of 4.47 ± 0.21 and 3.95 ± 0.61 µg/mL against HSV-1 and HSV-2, respectively. However, non-cytotoxic concentrations of both types of melittin produced only slight degrees of HSV-1 and HSV-2 inhibition after viral attachment, but melittin at 5 µg/mL was able to reduce the plaque size of HSV-2 when compared to the untreated group. In addition, MEL-AM and MEL-AF also exhibited anti-inflammatory activity via the inhibition of nitric oxide production in LPS-stimulated RAW 264.7 macrophage cells, and they were also found to down-regulate the expressions of the iNOS, COX-2 and IL-6 genes. The highest inhibition of IL-6 mRNA expression was found after treatment with 10 µg/mL of MEL-AM and MEL-AF. Therefore, melittin peptides have displayed strong potential to be used as an alternative treatment for HSV infection and inflammatory diseases in the future.

Integration of network pharmacology with experimental validation to reveal the mechanism of action of Longdan Xiegan Decoction against HSV2 infection and determine its effective components

Ethnopharmacological relevanceTraditional Chinese Medicine (TCM) has made enormous strides recently in the discovery of anti-herpes simplex virus (HSV) drugs under the guidance of TCM theory. Longdan Xiegan Decoction (LXD), a formulation recorded in the Pharmacopoeia of the People's Republic of China, has proved to be effective against HSV infection. However, its effective components and action mechanism remain unclear. Aim of the studyTo investigate the effective components and mechanisms of LXD in treating HSV infection based on network pharmacology and experimental validation. Materials and methodsThe anti-HSV activities of key compounds predicted by network analysis were detected by antiviral tests. High-performance liquid chromatography (HPLC) was applied to identify the main components of the LXD aqueous extract. Time-of-addition assay and infectivity inhibition reversibility assay were conducted to identify the potential antiviral mechanisms of licochalcone B (LCB). Additionally, we assessed the antiviral effect of LCB in vivo by use of body weight, viral load, histological analysis, and scoring of genital lesions in an HSV2-infected mouse model. ResultsOur data demonstrated that some components exhibited significant anti-HSV1/2 activity in vitro, including quercetin, kaempferol, wogonin, formononetin, naringenin, baicalein, isorhamnetin, glabridin, licochalcone A, echinatin, oroxylin A, isoliquiritigenin, pinocembrin, LCB and acacetin. HPLC analysis showed that LCB was the main component of LXD aqueous extract. In vitro experiments revealed that LCB not only inactivated HSV2 particles, but also inhibited HSV2 multiplication through the inhibition of the phosphorylation of Akt and its downstream targets. In vivo experiments confirmed that LCB could significantly reduce viral titer, delay weight loss, and alleviate pathological changes in vaginal tissue in vaginal infection mouse models. ConclusionLCB acted as the main component of LXD, with significant anti-HSV2 infection effects both in vivo and in vitro. This study provides additional evidence of the healing efficacy of LXD against HSV infection and presents an efficient analytical method for further investigation of the mechanisms of TCM in prevention and treatment of various diseases.

Anti-herpes simplex virus activities and mechanisms of marine derived compounds.

Herpes simplex virus (HSV) is the most widely prevalent herpes virus worldwide, and the herpetic encephalitis and genital herpes caused by HSV infection have caused serious harm to human health all over the world. Although many anti-HSV drugs such as nucleoside analogues have been ap-proved for clinical use during the past few decades, important issues, such as drug resistance, toxicity, and high cost of drugs, remain unresolved. Recently, the studies on the anti-HSV activities of marine natural products, such as marine polysaccharides, marine peptides and microbial secondary metabolites are attracting more and more attention all over the world. This review discusses the recent progress in research on the anti-HSV activities of these natural compounds obtained from marine organisms, relating to their structural features and the structure-activity relationships. In addition, the recent findings on the different anti-HSV mechanisms and molecular targets of marine compounds and their potential for therapeutic application will also be summarized in detail.

Flavonoids with Anti-Herpes Simplex Virus Properties: Deciphering Their Mechanisms in Disrupting the Viral Life Cycle.

The herpes simplex virus (HSV) is a double-stranded DNA human virus that causes persistent infections with recurrent outbreaks. HSV exists in two forms: HSV-1, responsible for oral herpes, and HSV-2, primarily causing genital herpes. Both types can lead to significant complications, including neurological issues. Conventional treatment, involving acyclovir and its derivatives, faces challenges due to drug resistance. This underscores the imperative for continual research and development of new drugs, with a particular emphasis on exploring the potential of natural antivirals. Flavonoids have demonstrated promise in combating various viruses, including those within the herpesvirus family. This review, delving into recent studies, reveals the intricate mechanisms by which flavonoids decode their antiviral capabilities against HSV. By disrupting key stages of the viral life cycle, such as attachment to host cells, entry, DNA replication, latency, and reactivation, flavonoids emerge as formidable contenders in the ongoing battle against HSV infections.

Integrating multi-index determination coupled with hierarchical cluster analysis to evaluate the quality consistency of PVE30, an anti-HSV "glycoprotein" macromolecule of Prunellae Spica.

Prunellae Spica (PS), derived from the dried fruit spikes of Prunella vulgaris L., is a traditional Chinese medicinal herb. Our previous studies found that PVE30, a water-extracting ethanol-precipitating "glycoprotein" macromolecule of PS, was a potential anti-herpes simplex virus (HSV) candidate. However, due to the complex structure and diverse bioactivity of the "glycoprotein", ensuring its quality consistency across different batches of PVE30 becomes particularly challenging. This poses a significant hurdle for new drug development based on PVE30. Our study aimed to integrate multi-index determination coupled with hierarchical cluster analysis (HCA) to holistically profile the quality consistency of "glycoprotein" in PVE30. High-performance gel permeation chromatography with refractive index detector (HPGPC-RID) was used to characterise the molecular weight (Mw) distribution, HPLC-PDA was used to quantitatively analyse the composed monosaccharides and amino acids, and UV-VIS was used to quantify the contents of polysaccharides and proteins. Qualitative and quantitative consistency was analysed for each single index in 16 batches of PVE30, and a 16 × 38 data matrix, coupled with HCA, was used to evaluate the holistic quality consistency of PVE30. The newly developed and validated methods were exclusive, linear, precise, accurate, and stable enough to quantify multi-indexes in PVE30. Single-index analysis revealed that 16 batches of PVE30 were qualitatively consistent in Mw distribution, polysaccharides and proteins, and the composition of composed monosaccharides and amino acids but quantitatively inconsistent in the relative contents of some "glycoprotein" macromolecules, as well as the composed monosaccharides/amino acids. HCA showed that the holistic quality of PVE30 was inconsistent, the inconsistency was uncorrelated with the regions where PS was commercially collected, and the contents of 17 amino acids and 2 monosaccharides contributed most to the holistic quality inconsistency. Multi-index determination coupled with HCA was successful in evaluating the quality consistency of PVE30, and the significant difference in quantitative indices was not caused by the origin of PS. The cultivating basis should be confirmed for PVE30-based new drug development.

Anti-Herpes Simplex Virus Type 1 Activity Evaluation of Natural Derived Phloroglucinol Derivatives and Their Molecular Mechanisms Study.

HSV-1 is a common infection that can cause cold sores. In this study, the anti-HSV-1 virus activity of three series compounds A1-A9, B1-B12, C1-C22 was screened by MTT assay, qRT-PCR assay, Western blot assay and viruses' plaque assays. The results of MTT assay disclosed that phloroglucinol derivatives C2 and C3 effectively inhibited the death of HSV-1 infected vero cells with the CC50 values of C2 and C3 were 72.64 μmol/L and 32.62 μmol/L in HaCaT cells, 137.6 μmol/L and 48.55 μmol/L in Hela cells. The IC50 values of C3 in vero cells and Hela cells were 19.26 μmol/L and 22.98 μmol/L, respectively. In the qRT-PCR experiments, it showed that C2 and C3 effectively reduced the synthesis of HSV-1 early viral gene VP16 and late viral gene gD. The Western blot results showed that both C2 and C3 inhibited the expression of HSV-1 gD protein in a concentration-dependent manner. Lastly, viruses' plaque assay results showed that C2 and C3 inhibited the production of HSV-1 progeny virus in Hela cells and HaCaT cells in a concentration-dependent manner. Taken together, these results suggest that C2 and C3 are promising candidate that warrants further attention in the development of anti-HSV-1 drugs.

Superior anti-pulmonary viral potential of Natrialba sp. M6-producing surfactin and C50 carotenoid pigment with unveiling its action modes

BackgroundRespiratory viruses, particularly adenoviruses (ADV), influenza A virus (e.g., H1N1), and coronaviruses (e.g., HCoV-229E and SARS-CoV-2) pose a global public health problem. Therefore, developing natural wide-spectrum antiviral compounds for disrupting the viral life cycle with antioxidant activity provides an efficient treatment approach. Herein, biosurfactant (Sur) and C50 carotenoid pigment (Pig) of haloalkaliphilic archaeon Natrialba sp. M6 which exhibited potent efficacy against hepatitis and anti-herpes simplex viruses, were investigated against pulmonary viruses.MethodsThe cytotoxicity of the extracted Sur and Pig was examined on susceptible cell lines for ADV, HIN1, HCoV-229E, and SARS-CoV-2. Their potential against the cytopathic activity of these viruses was detected with investigating the action modes (including, virucidal, anti-adsorption, and anti-replication), unveiling the main mechanisms, and using molecular docking analysis. Radical scavenging activity was determined and HPLC analysis for potent extract (Sur) was performed.ResultsAll current investigations stated higher anti-pulmonary viruses of Sur than Pig via mainly virucidal and/or anti-replicative modes. Moreover, Sur had stronger ADV’s capsid protein binding, ADV’s DNA polymerase inhibition, suppressing hemagglutinin and neuraminidase of H1N1, and inhibiting chymotrypsin-like (3CL) protease of SARS-CoV-2, supporting with in-silico analysis, as well as radical scavenging activity than Pig. HPLC analysis of Sur confirmed the predominate presence of surfactin in it.ConclusionThis study declared the promising efficacy of Sur as an efficient pharmacological treatment option for these pulmonary viruses and considered as guide for further in vivo research.

Inhibition of herpes simplex virus by wedelolactone via targeting viral envelope and cellular TBK1/IRF3 and SOCS1/STAT3 pathways

Development of novel antiherpes simplex virus (HSV) agents with active mechanisms different from nucleoside analogues is of high importance. Herein, we investigated the anti-HSV activities and mechanisms of wedelolactone (WDL) both in vitro and in vivo. Cytopathic effect (CPE) inhibition assay, plaque assay, and western blot assay were used to evaluate the anti-HSV effects of WDL in vitro. The immunofluorescence assay, RT-PCR assay, plaque reduction assay, sandwich ELISA assay, syncytium formation assay, tanscriptome analysis and western blot assay were used to explore the anti-HSV mechanisms of WDL. The murine encephalitis and vaginal models of HSV infection were performed to evaluate the anti-HSV effects of WDL in vivo. WDL possessed inhibitory effects against both HSV-1 and HSV-2 in different cells with low toxicity, superior to the effects of acyclovir. WDL can directly inactivate the HSV particle via destruction of viral envelope and block HSV replication process after virus adsorption, different from the mechanisms of acyclovir. WDL may influence the host genes and signaling pathways related to HSV infection and immune responses. WDL can mainly interfere with the TBK1/IRF3 and SOCS1/STAT3 pathways to reduce HSV infection and inflammatory responses. Importantly, WDL treatment markedly improved mice survival, attenuated inflammatory symptoms, and reduced the virus titres in both HSV-1 and HSV-2 infected mice. Thus, the natural compound WDL has the potential to be developed into a novel anti-HSV agent targeting both viral envelope and cellular TBK1/IRF3 and SOCS1/STAT3 pathways.

Acute liver failure due to herpes simplex viral hepatitis diagnosed by skin lesions and blood tests: a case report

BackgroundThe incidence of acute liver failure from herpes simplex virus is rare.Case presentationA 71-year-old Japanese man was diagnosed with acute liver failure and was transferred to our hospital. Steroid therapy, plasma exchange, and hemodiafiltration were started for liver failure, and antimicrobial therapy was initiated for pneumonia. Staphylococcus epidermidis was detected in blood culture. Skin rash appeared; a positive anti-herpes simplex virus result led to the diagnosis of acute liver failure from herpes simplex virus. Hence, acyclovir was started. After blood tests improved, treatments for acute liver failure were discontinued. Antimicrobial therapy was continued; however, he died. In this case, persistent bacteremia and drug-induced liver damage due to acyclovir may have contributed to his death.ConclusionsAcute liver failure can lead to complications and death. Thus, careful observation is crucial, even if the patient has shown some improvements.

1389 Local injection with anti-herpes simplex virus antibodies protects against development of herpes simplex virus–induced sweating disturbance

1389 Local injection with anti-herpes simplex virus antibodies protects against development of herpes simplex virus–induced sweating disturbance

Seroprevalence of Herpes Simplex Virus type-1antibodies (IgM,IgG) in smokers in Kirkuk city-Iraq

Herpes Simplex Virus type-1 (HSV-1) is classified in the α-herpes virus group of the Herpesviridae and HSV-1 infections are very common in the human population. The objective of this study is to determine the prevalence of anti-herpes simplex virus type-1 IgM and anti-herpes simplex virus type-1 IgG among smokers and nonsmokers. In the current study, A total of one hundred two serum samples from males were collected (70 smokers and 32 nonsmokers), there ages were ranged between 20- 50 year; this study which was done during the period between September 2014 to the January 2015. All obtained sera samples from all persons were tested using ELISA method for determine of Herpes simplex virus type-1 antibodies. Results in this study showed that the herpes simplex virus type-1 IgM seropositivity among smoker persons was 24 (34.3%). In addition, the result revealed that the percentage rate of the herpes simplex virus type-1 IgG among smokers was 61(87.1%). There was a significant effect of smoking on the seroprevalence of Herpes simplex virus type-1 antibodies (IgM , IgG).

Determination of anti-herpes simplex virus type 1 activity of the air filter coated with silver ions using a modified method of ISO 21702:2019

Determination of anti-herpes simplex virus type 1 activity of the air filter coated with silver ions using a modified method of ISO 21702:2019

Trends in anti-infective use during pregnancy in France between 2010 and 2019: a nationwide population-based study.

To describe the trends in anti-infective use during pregnancy between 2010 and 2019 and determine whether they were prescribed according to drug foetal safety international classification systems. We conducted a population-based, nationwide study using the French national health data system including all pregnancies ended between 2010 and 2019. Anti-infective agents were considered according to their pharmacological group and potential harmful risk using the Australian and Swedish classification systems. Prevalence rate was estimated annually and by trimester. Average annual percent change (AAPC) and 95% confidence intervals (CIs) were calculated using Joinpoint regression. Among 7 571 035 pregnancies, 3 027 031 (40.0%) received ≥1 antibacterial. This proportion decreased significantly from 41.5% in 2010 to 36.1% in 2019 (AAPC = -1.7%, [95%CI, -2.5 to -1.0%]). Conversely, use of antiviral agents increased during the 10-year study period for anti-herpes simplex virus agents (AAPC =4.4%, [3.7-5.2%]), influenza agents (AAPC = 25.4%, [6.2-48.1%]) and for HIV-antiretroviral agents (AAPC =1.3%, [0.6-2.0%]). Use of influenza vaccine increased from 0.2% in 2010 to 4.2% in 2019 (AAPC = 49.7%, [39.3-60.9%]). Among all pregnancies, 0.9% had been exposed to a potentially harmful anti-infective agent increasing from 0.7% in 2010 to 1.2% in 2019 (AAPC =6.4%, [4.4-8.5%]). Based on >7 million pregnancies identified from French nationwide data, this study showed that antibacterials are frequently prescribed during pregnancy although their use has decreased over the past 10 years. Our results suggest that anti-infective agents are generally prescribed in accordance with recommendations, although with a potential for improvement in influenza vaccination.

Anti-herpes simplex virus type Ⅰ of tectorigenin derivative and effect on Toll-like receptors in vitro

The study investigated the inhibitory effect and mechanism of tectorigenin derivative(SGY) against herpes simplex virus type Ⅰ(HSV-1) by in vitro experiments. The cytotoxicity of SGY and positive drug acyclovir(ACV) on African green monkey kidney(Vero) cells and mouse microglia(BV-2) cells was detected by cell counting kit-8(CCK-8) method, and the maximum non-toxic concentration and median toxic concentration(TC_(50)) of the drugs were calculated. After Vero cells were infected with HSV-1, the virulence was determined by cytopathologic effects(CPE) to calculate viral titers. The inhibitory effect of the tested drugs on HSV-1-induced cytopathy in Vero cells was measured, and their modes of action were initially explored by virus adsorption, replication and inactivation. The effects of the drugs on viral load of BV-2 cells 24 h after HSV-1 infection and the Toll-like receptor(TLR) mRNA expression were detected by real-time fluorescence quantitative PCR(RT-qPCR). The maximum non-toxic concentrations of SGY against Vero and BV-2 cells were 382.804 μg·mL~(-1) and 251.78 μg·mL~(-1), respectively, and TC_(50) was 1 749.98 μg·mL~(-1) and 2 977.50 μg·mL~(-1), respectively. In Vero cell model, the half maximal inhibitory concentration(IC_(50)) of SGY against HSV-1 was 54.49 μg·mL~(-1), and the selection index(SI) was 32.12, with the mode of action of significantly inhibiting replication and directly inactivating HSV-1. RT-qPCR results showed that SGY markedly reduced the viral load in cells. The virus model group had significantly increased relative expression of TLR2, TLR3 and tumor necrosis factor receptor-associated factor 3(TRAF3) and reduced relative expression of TLR9 as compared with normal group, and after SGY intervention, the expression of TLR2, TLR3 and TRAF3 was decreased to different degrees and that of TLR9 was enhanced. The expression of inflammatory factors inducible nitric oxide synthase(iNOS), tumor necrosis factor-α(TNF-α), and interleukin-1β(IL-1β) was remarkably increased in virus model group as compared with that in normal group, and the levels of these inflammatory factors dropped after SGY intervention. In conclusion, SGY significantly inhibited and directly inactivated HSV-1 in vitro. In addition, it modulated the expression of TLR2, TLR3 and TLR9 related pathways, and suppressed the increase of inflammatory factor levels.

Microbial Natural Products with Antiviral Activities, Including Anti-SARS-CoV-2: A Review.

The SARS-CoV-2 virus, which caused the COVID-19 infection, was discovered two and a half years ago. It caused a global pandemic, resulting in millions of deaths and substantial damage to the worldwide economy. Currently, only a few vaccines and antiviral drugs are available to combat SARS-CoV-2. However, there has been an increase in virus-related research, including exploring new drugs and their repurposing. Since discovering penicillin, natural products, particularly those derived from microbes, have been viewed as an abundant source of lead compounds for drug discovery. These compounds treat bacterial, fungal, parasitic, and viral infections. This review incorporates evidence from the available research publications on isolated and identified natural products derived from microbes with anti-hepatitis, anti-herpes simplex, anti-HIV, anti-influenza, anti-respiratory syncytial virus, and anti-SARS-CoV-2 properties. About 131 compounds with in vitro antiviral activity and 1 compound with both in vitro and in vivo activity have been isolated from microorganisms, and the mechanism of action for some of these compounds has been described. Recent reports have shown that natural products produced by the microbes, such as aurasperone A, neochinulin A and B, and aspulvinone D, M, and R, have potent in vitro anti-SARS-CoV-2 activity, targeting the main protease (Mpro). In the near and distant future, these molecules could be used to develop antiviral drugs for treating infections and preventing the spread of disease.

In Vitro Study of the Biological Potential of Wastewater Obtained after the Distillation of Four Bulgarian Oil-Bearing Roses.

The wastewater after rose oil distillation is usually discharged into the drainage systems and it represents a serious environmental problem. While being rich in polyphenols, which have beneficial biological activity and application in the pharmaceutical industry, limited research has been carried out about the biological activity of the specific wastewaters per se. Wastewaters after distillation of the four Bulgarian oil-bearing roses Rosa damascena Mill., R. alba L., R. centifolia L., and R. gallica L. exerted significant antioxidant activity and good antiherpes simplex virus type-1 (HSV-1) activity while maintaining a good toxicological safety profile (low cytotoxic effect) towards normal cell lines. More precisely, the non-tumorigenic cells were a human (HEK-293 embryonic kidney cells) and a mouse cell line (CCL-1 fibroblasts, which are recommended as a standard for cytotoxicity evaluation in Annex C of ISO 10993-5). The concentrations that achieved antioxidant and radical scavenging effects (0.04–0.92% v/v) were much lower than most of the maximum tolerated concentrations for the tissue culture cells (0.2–3.4% v/v). The wastewaters had a weak antiproliferative effect against Staphylococcus aureus. None of the wastewaters had activity against Gram-negative bacteria or a bactericidal or antifungal effect. We can conclude that these four species, which are the most preferred species worldwide for producing high-quality rose oil, have the potential to be developed as promising antioxidant and antiherpesvirus nutraceuticals.