Search

Background: Considering the role of calcium in the replication and morphogenesis of rotaviruses, it is hypothesized that decreased cytosolic calcium levels by using calcium channel blockers can subsequently interfere with rotavirus replication. Objective: The present study investigated the effects of two calcium ion channel blockers, amlodipine and diltiazem, against human rotavirus infection. Method: Cytotoxic effects of the drugs on MA-104 cells were evaluated using the neutral red assay. The effects of amlodipine and diltiazem at non-toxic concentrations on human rotavirus were examined using cytopathic effect inhibition, TCID50, and real-time PCR assays. Results: The highest inhibitory effect was obtained at concentrations of 0.5 μg/ml of amlodipine and 3 μg/ml of diltiazem, leading to 4.6 and 5.5 logarithmic reductions in infectious rotavirus titer and four- and a five-fold increase in the Ct values compared to the virus control, respectively (p-value Conclusion: Our study suggests that in addition to cardiovascular diseases, calcium channel blockers at their optimal doses may also be used to treat gastroenteritis caused by rotavirus infection

SARS-CoV-2 genome surveillance projects provide a good measure of transmission and monitor the circulating SARS-CoV-2 variants at regional and global scales. Iran is one of the most affected countries still involved with the virus circulating in at least five significant disease waves, as of September 2021. Complete genome sequencing of 50 viral isolates in an early phase of outbreak in Iran, shed light on the origins and circulating lineages at that time. As part of a genomic surveillance program, we provided an additional 319 complete genomes from October 2020 onwards. The current study is the report of complete SARS-CoV-2 genome sequences of Iran in the March 2020-May 2021 time interval. We aimed to characterize the genetic diversity of SARS-CoV-2 in Iran over one year. Overall, 35 different lineages and 8 clades were detected. Temporal dynamics of the prominent SARS-CoV-2 clades/lineages circulating in Iran is comparable to the global perspective and introduces the 19A clade (B.4) dominating the first disease wave, followed by 20A (B.1.36), 20B (B.1.1.413), 20I (B.1.1.7) clades, dominating second, third and fourth disease waves, respectively. We observed a mixture of circulating 20A (B.1.36), 20B (B.1.1.413), 20I (B.1.1.7) clades in winter 2021, paralleled in a diminishing manner for 20A/20B and a growing rise for 20I, eventually prompting the 4th outbreak peak. Furthermore, our study provides evidence on the entry of the Delta variant in April 2021, leading to the 5th disease wave in summer 2021. Three lineages are highlighted as hallmarks of SARS-CoV-2 outbreak in Iran; B4, dominating early periods of the epidemic, B.1.1.413 (specific B.1.1 lineage carrying a combination of [D138Y-S477N-D614G] spike mutations) in October 2020-February 2021, and the co-occurrence of [I100T-L699I] spike mutations in half of B.1.1.7 sequences mediating the fourth peak. Continuous monthly monitoring of SARS-CoV-2 genome mutations led to the detection of 1577 distinct nucleotide mutations, in which the top recurrent mutations were D614G, P323L, R203K/G204R, 3037C>T, and 241C>T; the renowned combination of mutations in G and GH clades. The most frequent spike mutation is D614G followed by 13 other frequent mutations based on the prominent circulating lineages; B.1.1.7 (H69_V70del, Y144del, N501Y, A570D, P681H, T716I, S982A, D1118H, I100T, and L699I), B.1.1.413 (D138Y, S477N) and B.1.36 (I210del). In brief, mutation surveillance in this study provided a real-time comprehensive picture of the SARS-CoV-2 mutation profile in Iran, which is beneficial for evaluating the magnitude of the epidemic and assessment of vaccine and therapeutic efficiency in this population.

Leishmaniosis, a vector-born disease that infects humans and other vertebrates, is the result of infection with Leishmania species belong to the family Trypanosomatidae. The present study was performed to determine the status of cutaneous leishmaniosis in Isfahan province. Samples were taken from the margin of skin ulcers of patients with suspected CL referred to the medical health centers in Isfahan province. Also, ear and snout samples were taken from the rodents. In total, 85 parasitologically positive samples were subjected to the PCR-RFLP method based on the nagt gene for identification of Leishmania species, also 11 samples were subjected to sequencing and phylogenetic analysis. For all positive samples, a 1450-1460 bp band of the nagt gene was amplified in PCR method. The digestion pattern of ACC1 enzyme in 79 of patients indicated L. major and in one sample was similar to L. tropica. Four rodent reservoirs distingue as L. major and one sample as L. turanica. Phylogenetic analysis confirmed the species identification and three haplotypes were reported. The results of the current study showed that L. major is the predominant species of Leishmania parasites in Isfahan province and the main reservoir of CL is Rhombomys opimus. Also, the nagt gene is a useful and practical marker for determining different species of Leishmania parasites as well as their phylogenetic analysis.

In this pandemic SARS-CoV-2 crisis, any attempt to contain and eliminate the virus will also stop its spread and consequently decrease the risk of severe illness and death. While ozone treatment has been suggested as an effective disinfection process, no precise mechanism of action has been previously reported. This study aimed to further investigate the effect of ozone treatment on SARS-CoV-2. Therefore, virus collected from nasopharyngeal and oropharyngeal swab and sputum samples from symptomatic patients was exposed to ozone for different exposure times. The virus morphology and structure were monitored and analyzed through Atomic Force Microscopy (AFM), Transmission Electron Microscopy (TEM), Atomic Absorption Spectroscopy (AAS), and ATR-FTIR. The obtained results showed that ozone treatment not only unsettles the virus morphology but also alters the virus proteins’ structure and conformation through amino acid disturbance and Zn ion release from the virus non-structural proteins. These results could provide a clearer pathway for virus elimination and therapeutics preparation.

Background: Detection of Leishmania RNA virus (LRV) in Old World Leishmania species and their possible role in the disease prognosis requires sensitive and specific methods, preferably independent of the viral genome. We aimed to develop an indirect immunofluorescence antibody (IFA) assay to detect LRV in the Old World Leishmania parasites. Methods: Clinical samples were collected from 86 cutaneous leishmaniasis (CL) patients in different endemic areas of CL in Iran, during 2017-2019. For antibody preparation, the viruses were obtained from sediment of an LRV-infected L. major culture-using freeze and thaw cycles followed by gradient cesium chloride centrifugation. The purified viruses were used to immunize a male 3-4 months rabbit. Various dilutions of the LRV-immunized rabbit's serum and a conjugated antibody were deployed to detect LRV in 48 isolates by IFA assay. Results: LRV virus was detected in four of the 48 CL cases using IFA method. Amplification of a partial fragment of RNA-dependent RNA polymerase (RdRp) gene from the isolates confirmed the IFA results. In phylogeny, the generated RdRp sequences from four isolates were grouped with the other Old World LRVs, but separate from L. aethiopica LRVs, which appeared as a highly supported distinct clade. Conclusion: Further optimization of this approach to detect the LRV directly in lesion scrapings can make it a more reliable tool for field studies and disclosing the virus's possible role in disseminating and unusual clinical features.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the pathogenesis is unclear. Host genetic background is one of the main factors influencing the patients' susceptibility to several viral infectious diseases. This study aimed to investigate the association between host genetic polymorphisms of two genes, including vitamin D receptor (VDR) and vitamin D binding protein (DBP), and susceptibility to COVID-19 in a sample of the Iranian population. This case-control study enrolled 188 hospitalized COVID-19 patients as the case group and 218 suspected COVID-19 patients with mild signs as the control group. The VDR (rs7975232, rs731236 and rs2228570) and DBP (rs7041) gene single nucleotide polymorphisms (SNPs) were genotyped by Polymerase Chain Reaction Restriction - Fragment Length Polymorphism (PCR-RFLP) method. A significant association between rs2228570 SNP in the VDR gene and the susceptibility of COVID-19 was found between case and control groups. The CT genotype (Heterozygous) of rs2228570 C T polymorphism showed significant association with a 3.088 fold increased odds of COVID-19 (p .0001; adjusted OR: 3.088; 95% CI: 1.902-5.012). In addition, a significant association between CC genotype of rs2228570 CT polymorphism and increased odds of COVID-19 in male and female groups (p = .001; adjusted OR: 3.125; 95% CI: 1.630-5.991 and p = .002; adjusted OR: 3.071; 95% CI: 1.485-6.354 respectively) were determined. Our results revealed no significant differences in the frequency of genotype and allele of VDR (rs7975232 and rs731236) and DBP (rs7041) between SARS-CoV-2-infected patients and controls (p .05). Our results showed that polymorphism of VDR (rs2228570) probably could influence individual susceptibility to COVID-19. The polymorphisms of VDR (rs7975232 and rs731236) and DBP (rs7041) were not associated with SARS-CoV-2 infection susceptibility.

Hepatitis B virus (HBV), along with Hepatitis C virus chronic infection, represents a major risk factor for hepatocellular carcinoma (HCC) development. However, molecular mechanisms involved in the development of HCC are not yet completely understood. Recent studies have indicated that mutations in CTNNB1 gene encoding for β-catenin protein lead to aberrant activation of the Wnt/ β-catenin pathway. The mutations in turn activate several downstream genes, including c-Myc, promoting the neoplastic process. The present study evaluated the mutational profile of the CTNNB1 gene and expression levels of CTNNB1 and c-Myc genes in HBV-related HCC, as well as in cirrhotic and control tissues. Mutational analysis of the β-catenin gene and HBV genotyping were conducted by direct sequencing. Expression of β-catenin and c-Myc genes was assessed using real-time PCR. Among the HCC cases, 18.1% showed missense point mutation in exon 3 of CTNNB1, more frequently in codons 32, 33, 38 and 45. The frequency of mutation in the hotspots of exon 3 was significantly higher in non-viral HCCs (29.4%) rather than HBV-related cases (12.7%, P = 0.021). The expression of β-catenin and c-Myc genes was found upregulated in cirrhotic tissues in association with HBV infection. Mutations at both phosphorylation and neighboring sites were associated with increased activity of the Wnt pathway. The results demonstrated that mutated β-catenin caused activation of the Wnt pathway, but the rate of CTNNB1 gene mutations was not related to HBV infection. HBV factors may deregulate the Wnt pathway by causing epigenetic alterations in the HBV-related HCC.

Background:The advent of resistance-associated mutations in HIV-1 is a barrier to the success of the ARTs.Objective:In this study, the abundance of HIV-1 infection in Iranian children, and also detection of the TDR in naïve HIV-1 infected pediatric (under 12 years old) were evaluated.Materials:From June 2014 to January 2019, a total of 544 consecutive treatment-naïve HIV-1- infected individuals enrolled in this study. After RNA extraction, amplification, and sequencing of the HIV-1 pol gene, the DRM and phylogenetic analysis were successfully performed on the plasma specimens of the ART-naïve HIV-1-infected-children under 12 years old. The DRMs were recognized using the Stanford HIV Drug Resistance Database.Results:Out of the 544 evaluated treatment-naïve HIV-1-infected individuals, 15 (2.8%) cases were children under 12 years old. The phylogenetic analyses of the amplified region of pol gene indicated that all of the 15 HIV-1-infected pediatric patients were infected by CRF35_AD, and a total of 13.3% (2/15) of these children were infected with HIV-1 variants with SDRMs (one child harbored two related SDRMs [D67N, V179F], and another child had three related SDRMs [M184V, T215F, and K103N]), according to the last algorithm of the WHO. No PIs-related SDRMs were observed in HIV-1-infected children.Conclusion:The current study demonstrated that a total of 13.3% of treatment-naïve HIV-1-infected Iranian pediatrics (under 12 years old) were infected with HIV-1 variants with SDRMs. Therefore, it seems that screening to recognize resistance-associated mutations before the initiation of ARTs among Iranian children is essential for favorable medication efficacy and dependable prognosis.

Background Human papilloma virus (HPV) causes the most common sexually-transmitted infection especially among sexually-active individuals. The aim of study was to characterize the molecular characterization of HPV genotypes between 5176 female and male patients. Methods HPV DNA was extracted from genital swabs of the study participants and amplified by Real Time Polymerase Chain Reaction (PCR). Genotyping was performed for 2525 cases using REALQUALITY RQ-Multi HPV Detection Kit for the identification of 14 high risk (HR) and 2 low risk (LR) HPV genotypes. Demographic figures were analyzed in correlation with virological data statistically. Results Out of 5176 cases from 7 laboratories, 2727 (53%) were positive for HPV, of which. 2372(87%) women and 355 (13%) men were HPV positive. However, in an intra-gender analysis, positive rate was higher in men (355/637, 55.7%) than in women (2372/4539, 52%; P value 0.007). HPV positive patients were younger than negative individuals. Positive rate was higher among age categories 20–40. Genotyping was performed for 2525 cases. Out of 1219 (48%) patients who contained single genotypes, 566 (22%) and 653 (26%) harboured HR and LR genotypes, respectively. In females and males, 1189 (54%) and 117 (37%) contained multiple genotypes. No substantial associations were found between different age categories and HR/LR and multiple genotypes distribution. Conclusion The prevalence of HPV infection in both genders was high. However, men had a higher rate of infection. These observations highlighted the necessity for a plan for targeted education to younger population in the society as well as application of infection control measures against HPV infection, especially in terms of general population mass HPV vaccination.

Detection ofClinical samples were collected from 86 cutaneous leishmaniasis (CL) patients in different endemic areas of CL in Iran, during 2017-2019. For antibody preparation, the viruses were obtained from sediment of an LRV-infectedLRV virus was detected in four of the 48 CL cases using IFA method. Amplification of a partial fragment of RNA-dependent RNA polymerase (Further optimization of this approach to detect the LRV directly in lesion scrapings can make it a more reliable tool for field studies and disclosing the virus's possible role in disseminating and unusual clinical features.

Background: Limited sources of fresh water necessitate the application of health policies for treatment and decontamination of human sewage for further use. A wide variety of infectious agents, including bacteria, fungi, parasites, and viruses, can be found in sewage. Enteric viruses such as hepatitis A virus (HAV) can survive the current treatments and infect susceptible hosts. Objectives: This study aimed to evaluate HAV contamination in human sewage before and after treatment in the wastewater treatment plant of Ekbatan town in Tehran, Iran, and analyze the phylogenetic properties of the identified viruses. Methods: Over a 12-month period, we collected the wastewater samples including influent, before chlorination, and effluent, from the wastewater treatment plant of Ekbatan town in Tehran, Iran. Ribonucleic acid (RNA) extraction, complementary deoxyribonucleic acid (cDNA) synthesis, and semi-nested polymerase chain reaction (PCR) were performed to identify HAV contamination. Phylogenetic analysis was performed to investigate subgenotypes of the virus. Results: HAV was detected in all influents and samples before chlorination, while the virus was detected in 50% of the effluent samples. All detected viruses belonged to subgenotype IB. Conclusions: Investigating the presence of HAV in sewage provides a general picture of the virus spread in the population of interest. HAV was detected in all influent samples, indicating that the infection is endemic in this area all year round. This also indicates the inability of the current treatment protocols in virus removal, which can be a threat to the public health.

A quantitative model on exposure to pathogenic viruses in air of recreational area and their corresponding health effects is necessary to provide mitigation actions in content of emergency response plans (ERP). Here, the health risk associated with exposure to two pathogenic viruses of concern: Rotavirus (RoV) and Norovirus (NoV) in air of water spray park were estimated using a quantitative microbial risk assessment (QMRA) model. To this end, real-time Reverse Transcriptase polymerase chain reaction (real-time RT-PCR) was employed to measure the concentration levels of RoV and NoV over a twelve-month period. The probability of infection, illness and diseases burden of gastrointestinal illness (GI) caused by RoV and NoV for both workers and visitors were estimated using QMRA and Monto-Carlo simulation technique. The annual mean concentration for RoV and NoV in sampling air of water spray park were 20and 1754, respectively. The %95 confidence interval (CI) calculated annual DALY indicator for RoV (Workers: 2.62 × 10

Background Rotavirus is the most prevalent cause of severe gastroenteritis, hospitalizations, and deaths among infants and young children, globally. No specific antiviral drug is available against rotavirus infection. Objective The current study aimed to assess the antiviral effect of human cathelicidin antimicrobial peptide LL-37 on rotavirus infection in vitro. Methods This study was conducted in the laboratory conditions of Iran University of Medical Sciences, in Tehran City, Iran. The neutral red assay was performed to assess the cytotoxicity of different concentrations of the peptide on the MA-104 cell line, and its antiviral activity was determined by TCID50 (50% tissue culture infective dose) assay. Findings According to the cytotoxicity results, viability maintained more than 90% up to the concentration of 50 μg/mL of LL-37 peptide. The antiviral assays results revealed that the concentration of 50 μg/mL LL-37 peptide could significantly reduce (3.36 log10 TCID50) the production of rotavirus progeny when administered before virus exposure (P= 0.0001). However, no inhibitory effect was detected after cell exposure to virus. Conclusion The obtained data suggested that LL-37 can be considered as a new antiviral agent for protecting infants and young children against gastroenteritis caused by rotaviruses. However, further in vivo investigations are required to confirm this finding.

LL-37 is a 37 amino acid long cationic peptide belonging to the cathelicidin family of antimicrobial peptides. Limited investigations have shown the antimicrobial potency of LL-37 against different viral infections. We aimed to investigate the effect of the human cathelicidin peptide LL-37 on rotavirus infection, as a causative agent of severe gastroenteritis in children. After evaluation of LL-37 toxicity using methyl thiazolyl tetrazolium and neutral red uptake assays on the MA-104 cells, antiviral activity was assessed both by tissue culture infectious dose 50 (TCID50) and quantitative Real-Time PCR assays. Indirect immunofluorescence assay (IFA) and hematoxylin and eosin (H&E) staining were also performed to further confirm the inhibitory effects of the LL-37 on rotavirus. The viability maintained more than 90% up to the concentration of 50 μg/mL of peptide. LL-37 exerted its antiviral effect only when cells were pre-treated with peptide prior to rotavirus infection. 50 μg/mL of LL-37 could result in 3.36 log10 TCID50 reduction in virus titer (p = 0.0001), and an inhibition rate of 82.2% in copy number of rotavirus genomic RNA was obtained. IFA showed that the expression of rotavirus antigens in cells pre-treated with 50 μg/mL LL-37 is noticeably lower than the virus control. H&E assay also showed that the size and formation of inclusion bodies are decreased in rotavirus-infected cells pre-treated with 50 μg/mL LL-37 as compared to the virus control. Our findings suggested that the LL-37 peptide may interfere with viral attachment or act as an immune regulator, promoting innate immune responses.

Background: Early diagnosis of immunodeficiency virus-1 infection in children and access to treatment for this infection is critical in decreasing infant mortality. Objectives: The aim of the current survey was to determine the presence of HIV-1 genomic RNA in plasma and proviral DNA in peripheral blood mononuclear cell (PBMC) specimens of neonates born to HIV-infected mothers. Methods: From March 2014 to February 2018, 73 neonates born to HIV-1-infected mothers covered by the prevention of mother-to-child transmission (PMTCT) program were enrolled in this study to compare two different diagnostic methods. After the extraction of viral RNA of plasma and genomic DNA of PBMC specimens, HIV-1 RNA and proviral DNA was tested by amplification of the long terminal repeat (LTR) region of HIV-1 using real-time PCR. Results: Out of 73 evaluated infants, 41 infants (56.2%) were male. The average age of the mothers with HIV-1 infection was 30.7 ± 5.2 (range: 19–47) years. The results revealed that none of the infants were infected with HIV-1, and also all were negative for HIV-1 genomic RNA in plasma specimen and proviral DNA of HIV-1 in PMBC samples. During the present study, 20 infants born to HIV-1 positive mothers who were not included in the PMTCT project were accidentally identified. Four infants (20%) out of these 20 infants were infected with HIV, all were infected with CRF35-AD of HIV, and none carried variants with surveillance drug-resistant mutations. Conclusions: The results of the present study showed that two molecular methods of detecting HIV infection (presence of genomic RNA of HIV-1 in plasma and proviral DNA of HIV-1 in PBMC specimens) are completely in agreement with each other, and the PMTCT program is possibly an effective program.

BACKGROUND Hepatocellular carcinoma (HCC) is the most common type of liver cancer around the world. Since this cancer is highly resistant to the existing treatments, we used a novel method, which selectively targets HCC cancer cells to improve the treatment process. As normal cells are resistant to reovirus replication, we used oncolytic reoviruses, which can infect, replicate in, and destroy cancer cells. In this study, the effects of oncolytic human reoviruses on cancer cells, derived from HCC biopsies, were investigated. METHODS First, reoviruses were purified. Then a plaque assay was performed to estimate the number of viruses and determine the multiplicity of infection (MOI). To evaluate the effects of reoviruses on cancer cells derived from HCC biopsies, replication of reovirus RNA, viral protein production, cytopathic effects (CPE), and cancer cell viability were assessed at different intervals post-infection. RESULTS Replication of reovirus RNA and viral protein production were detected in cancer cells. Also, different levels of viral protein production, CPE, cytotoxicity, and cancer cell viability were observed at different intervals post-infection with human reoviruses. In contrast, normal human fibroblasts, which were used as negative control, remained unchanged. CONCLUSIONS For the first time, the effects of human reoviruses on HCC biopsies were investigated. The results showed that human reoviruses could replicate in and destroy cancer cells derived from HCC biopsies. Overall, human reoviruses can be potentially used for the treatment of HCC.

Leishmania RNA virus (LRV) is a double-strand RNA virus that was first detected in members of the Leishmania viannia in the New World. The present study aimed to investigate the presence of LRV in the Leishmania species isolated from cutaneous leishmaniasis (CL) patients and rodents as reservoirs in Isfahan province an old zoonotic CL focus, center of Iran. Totally, 85 samples were collected from CL patients (n = 80) and rodent reservoirs (n = 5) from different regions of Isfahan province. Species identification was determined using the PCR-RFLP method. Viral dsRNA was extracted and for observation of 5.3 kb dsRNA on an agarose gel. The presence of LRV was surveyed using the Semi-nested PCR method. For phylogenetic analyzes, 6 samples of 13 isolates were sequenced and a phylogenetic tree was drawn by MEGA7 version 7.0.26. Of 80 Leishmania isolates recovered from the patients with CL, 79 and only one were identified as L. major and L. tropica, respectively. Also, the PCR assays detected four L. major and one L. turanica in five assessed Rhombomys opimus as the rodent reservoirs. LRV was detected only in Leishmania species isolated from 13 species of 85 (15.3%) CL including (L. major, n = 12) and (L. tropica, n = 1). Phylogenetic analysis showed that they were belonged to LRV2 and had the highest similarity with Iranian reference LRV2 in GenBank. Our results showed that the LRV2 was present in cutaneous Leishmania species in Isfahan province is the most historical and touristic province of Iran. In the study LRV was not reported from rodent reservoirs, it may be due to the small sample size. Phylogenetic analysis of current sequences demonstrated that these isolates belong to the registered LRV2 of the Old World.

Objective LeishmaniaRNA virus (LRV) is a double-stranded RNA (dsRNA) virus that circulates within many species of the Leishmania parasite. In this study, we aimed to investigate the presence of LRV2 circulating in Leishmania isolates in an old focus of ZCL located in northeastern of Iran. Methods Leishmania isolates were collected from 85 patients that confirmed to have cutaneous leishmaniasis (CL) based on parasitological examination. To identify the Leishmania isolates, species-specific primer sets were applied for molecular identification. The presence of LRV2 was performed by RdRp-semi nested-PCR. The genetic diversity were calculated using MEGA and DnaSP. To assess haplotype diversity, 31 LRV2 strains in different regions were surveyed using analysis a 292-bp section of the RdRp sequences. Results Out of 85 patients, 83 (97.6 %) were diagnosed withL. major and 2 (2.4 %) with L. tropica. LRV2 virus was detected in 59 (69.4%) of the CL cases. For the first time, LRV2 was reported in one L. tropica strain in Iran. The current LRV2 sequences indicated the highest similarities to an Old World LRV2. Moreover, 10 unique haplotypes were identified based on the analyzed sequences of the RdRp gene. Conclusions Our results indicated the highest occurrence ofLeishmania/LRV2 co-circulation in this known ZCL focus from northeastern Iran. Phylogenetic analyses of LRV2 sequences confirmed that these isolates belong to the order of LRV2 from the Old World. This study offered an insight into LRV2 haplotype, that the issue informative and can be used for genetic research of LRV2 in other regions.

Background: The emergence of drug-resistant strains of herpes simplex virus type 1 (HSV-1) has been increasingly reported. Therefore, attempts to discover new antiviral agents in particular from natural compounds are required. In this study, we evaluated the possible inhibitory effects of hydroalcoholic extract of Sambucus ebulus (S. ebulus ) against HSV-1. Methods: S. ebulus extract was produced by maceration method. MTT assay was used to evaluate the cytotoxicity effects of the S. ebulus extract; also, antiviral effects were measured both by test TCID50 and quantitative real-time PCR methods. To study the inhibitory impact of S. ebulus extract on the expression of HSV-1 antigens, indirect immunofluorescence assay (IFA) was also performed. All analyses were performed using the GraphPad Prism software v. 7.0. Results: In the postexposure assay of HSV-1 with S. ebulus extract at the highest nontoxic concentration (75 μg/mL), S. ebulus extract led to 2.6 log10 TCID50 reduction in infectious virus titer. At the highest nontoxic concentration, the S. ebulus extract led to inhibition rates of 91.2%, based on the quantitative real-time PCR assay results (p

Additional file 1: Figure S1. The electrophoresis of RNAs on agarose gel. Figure S2. PCR products of β-catenin exons 3–5 on agarose gel. Figure S3. Unknown point mutations observed in exons 3–5 in the β-catenin among HCC samples. Table S1. List of mutations observed in this study.

Background Some studies implicate rotavirus infection as a trigger for the development of type 1 diabetes mellitus (T1DM) in children, however findings are controversial. Objectives We investigated the link between rotavirus infection and autoantibodies against islet antigens and T1DM in children. Methods Serum samples from 80 new-onset diabetic and 80 nondiabetic children were screened for anti-rotavirus IgG, anti-GAD65 and anti-IA-2 autoantibodies using ELISA kits. Results Positivity percentages of anti-rotavirus IgG detection in diabetic and nondiabetic children were 51.3% and 35.0%, respectively (p = 0.03). The mean anti-GAD65 and anti-IA-2 antibody titers in anti-rotavirus IgG positive samples were statistically higher than that the anti-rotavirus IgG negative samples. A positive correlation was found between anti-rotavirus IgG and anti-GAD65 antibody levels (p = 0.004; r = 0.22). Conclusions Our findings support the hypothesis that rotovirus infection may induce T1DM in children.

Occult HCV infection (OCI) has been described as the presence of hepatitis C virus (HCV) genomic RNA in hepatocytes and/or peripheral blood mononuclear cell (PBMC) specimens and the lack of HCV genomic RNA and anti-HCV antibodies (Abs) in plasma samples. Injection drug users (IDUs) are the most important high-risk group for infection with blood-borne viruses, particularly HCV. The purpose of this study was to determine the presence of OCI in IDUs. A prospective cross-sectional study of 126 consecutive Iranian IDUs was performed from March 2017 to January 2018. PBMCs were separated from blood samples from the participants, and after extraction of the viral RNA from the plasma and PBMC specimens, HCV RNA was detected in the samples using RT-nested PCR by amplification of the 5'-NTR of HCV. HCV genotyping was carried out using restriction a fragment length polymorphism (RFLP) assay. The viral RNA was amplified using RT-nested PCR with specific primers for the NS5B gene, and the PCR products were sequenced to confirm the results obtained by HCV RNA detection and HCV genotyping. Out of the 126 IDUs studied, 105 (83.3%) were negative for anti-HCV Abs and HCV RNA in plasma samples, whereas HCV RNA was detected in the PBMC samples of six (5.7%) participants, indicating that these individuals had OCI. Moreover, HCV genomic RNA was detected in PBMC samples from five (23.8%) of the 21 IDUs studied who were positive for anti-HCV Abs and negative for HCV genomic RNA in plasma specimens. These IDUs also had OCI. The HCV genotypes in the PBMC samples from the subjects with OCI were determined. Six (54.5%) subjects were infected with HCV subtype 3a, and five (45.5%) were infected with HCV subtype 1a. This study showed that 8.7% of the Iranian IDUs had OCI, and therefore, a study focusing on the diagnosis of OCI in these individuals can be valuable and informative.

Aim: We aimed to determine the possible inhibitory effects of zinc oxide nanoparticles (ZnO–NPs) and polyethylene glycol (PEG)-coated ZnO–NPs (ZnO–PEG–NPs) on herpes simplex virus type 1 (HSV-1). Materials & methods: PEGylated ZnO–NPs were synthesized by the mechanical method. Antiviral activity was assessed by 50% tissue culture infectious dose (TCID50) and real-time PCR assays. To confirm the antiviral activity of ZnO–NPs on expression of HSV-1 antigens, indirect immunofluorescence assay was also conducted. Results: 200 μg/ml ZnO–PEG–NPs could result in 2.5 log10 TCID50 reduction in virus titer, with inhibition rate of approximately 92% in copy number of HSV-1 genomic DNA. Conclusion: ZnO–PEG–NPs could be proposed as a new agent for efficient HSV-1 inhibition. Our results indicated that PEGylation is effective in reducing cytotoxicity and increasing antiviral activity of nanoparticles.

Hepatitis B virus (HBV), along with Hepatitis C virus chronic infection, represents a major risk factor for hepatocellular carcinoma (HCC) development. However, molecular mechanisms involved in the development of HCC are not yet completely understood. Recent studies have indicated that mutations in CTNNB1 gene encoding for β-catenin protein lead to aberrant activation of the Wnt/ β-catenin pathway. The mutations in turn activate several downstream genes, including c-Myc, promoting the neoplastic process. The present study evaluated the mutational profile of the CTNNB1 gene and expression levels of CTNNB1 and c-Myc genes in HBV-related HCC, as well as in cirrhotic and control tissues. Mutational analysis of the β-catenin gene and HBV genotyping were conducted by direct sequencing. Expression of β-catenin and c-Myc genes was assessed using real-time PCR. Among the HCC cases, 18.1% showed missense point mutation in exon 3 of CTNNB1, more frequently in codons 32, 33, 38 and 45. The frequency of mutation in the hotspots of exon 3 was significantly higher in non-viral HCCs (29.4%) rather than HBV-related cases (12.7%, P = 0.021). The expression of β-catenin and c-Myc genes was found upregulated in cirrhotic tissues in association with HBV infection. Mutations at both phosphorylation and neighboring sites were associated with increased activity of the Wnt pathway. The results demonstrated that mutated β-catenin caused activation of the Wnt pathway, but the rate of CTNNB1 gene mutations was not related to HBV infection. HBV factors may deregulate the Wnt pathway by causing epigenetic alterations in the HBV-related HCC.

Background Epstein-Barr virus (EBV) is associated with different malignant diseases, such as Hodgkin lymphoma (HL) and lymphoproliferative disorders. Patients with hematologic malignancies by variable severity could be suspected for the infection with different types of this virus. This preliminary study reported the genotyping and related viral load of Epstein-Barr virus in Iranian patients with hematologic malignancies for estimation of possible factors affecting malignancy. Methods Peripheral blood mononuclear cells (PBMC) of HL (n=20), NHL (n=29), acute lymphocytic leukemia (ALL) (n=18) and chronic lymphocytic leukemia (CLL) (n=12) were obtained. After DNA extraction, a nested-PCR and a conventional-PCR targeting EBNA-2 and EBNA-3C genes were performed. A real-time PCR assay for viral load quantitation carried out. Standard curve analysis used for evaluation of amplification specificity. Results Of 79 included patients, 34 (43%) were EBV positive. There were 23.5% (8/34), 38.2% (13/34), 23.5% (8/34), 14.8% (5/34) in HL, NHL, ALL and CLL groups, respectively. Also, the main genotype was genotype I (91.2%) which it follows by 8.8% (3/34) genotype II. The real-time PCR assay showed the mean viral load ± std. deviation was 2.75×105 ± 1.202×106 copies/μg DNA and the higher viral load was seen in NHL patients. Conclusion This preliminary investigation in Iran shows that the main EBV genotype into our region probably is genotype I (91.2%) which it is similar to others. We could not find any statistically significant association between the virus infection and viral load with any specific disease and patients' demographic data. .

Background Currently available anti-influenza drugs are often associated with limitations such as toxicity and the appearance of drug-resistant strains. Therefore, there is a pressing need for the development of novel, safe and more efficient antiviral agents. In this study, we evaluated the antiviral activity of zinc oxide nanoparticles (ZnO-NPs) and PEGylated zinc oxide nanoparticles against H1N1 influenza virus. Methods The nanoparticles were characterized using the inductively coupled plasma mass spectrometry, x-ray diffraction analysis, and electron microscopy. MTT assay was applied to assess the cytotoxicity of the nanoparticles, and anti-influenza activity was determined by TCID50 and quantitative Real-Time PCR assays. To study the inhibitory impact of nanoparticles on the expression of viral antigens, an indirect immunofluorescence assay was also performed. Results Post-exposure of influenza virus with PEGylated ZnO-NPs and bare ZnO-NPs at the highest non-toxic concentrations could be led to 2.8 and 1.2 log10 TCID50 reduction in virus titer when compared to the virus control, respectively (P Conclusions Taken together, our study indicated that PEGylated ZnO-NPs could be a novel, effective, and promising antiviral agent against H1N1 influenza virus infection, and future studies can be designed to explore the exact antiviral mechanism of these nanoparticles.

The latest class of antiretrovirals (ARVs), including integrase strand transfer inhibitors (INSTIs), has been demonstrated to be effective for antiretroviral therapy (ART). Despite all the distinguishing characteristics of these drugs, including a high genetic barrier to resistance and lower toxicity than other ARVs, unfortunately, INSTI drug resistance mutations (DRMs) have occasionally been observed. The aim of this study was to investigate the presence of DRMs associated with INSTIs among treatment-experienced HIV-1-infected patients. From June 2012 to December 2018, a total of 655 treatment-experienced HIV-1-infected patients enrolled in this cross-sectional survey. Following amplification and sequencing of the HIV-1 integrase region of the pol gene, DRM and phylogenetic analysis were successfully carried out on the plasma samples of patients who had a viral load over 1,000 IU/ml after at least 6 months of ART. Out of the 655 patients evaluated, 62 (9.5%) had a viral load higher than 1,000 IU/ml after at least 6 months of ART. Phylogenetic analysis showed that all of the 62 HIV-1 patients experiencing treatment failure were infected with CRF35_AD, and one of these patients (1.6%) was infected with HIV-1 variants with DRMs. The DRMs that were identified belonged to the INSTI class, including E138K, G140A, S147G, and Q148R. This survey shows that DRMs belonging to the INSTI class were detected in an Iranian HIV patient who has experienced treatment failure. Therefore, regarding the presence of DRMs to INSTIs in ART-experienced patients, it seems better to perform drug resistance mutation testing in HIV patients experiencing treatment failure before changing the ART regimen and prescribing this class of medication.

From a health prospective, it is critical to provide a comprehensive model which integrates all the parameters involved in virus transmission and its consequences on human body. In order to estimate the health risks, for workers and residents, associated with an exposure airborne viruses emitted from a wastewater treatment (WWTP), the concentration levels of viruses in emitted bioaerosols over a twelve-month period were measured by real-time polymerase chain reaction (RT-PCR). A combined Gaussian plum dispersion model and quantitative microbial risk assessment (QMRA) with Monte-Carlo simulation served as suitable explanatory tools to estimate the risk of acquiring gastrointestinal illness (GI) due to exposure to air containing Rotavirus (RoV) and Norovirus (NoV) bioaerosols. Additionally, DALY metric was applied to quantify the disability and mortality for workers and residents. RoV and NoV were detected above aeration tank with annual mean concentration 27 and 3099 (Viruses/m3.h), respectively. The medium calculated DALY indicator based on viral loads in contaminant source (RoV:5.76 × 10−2 and NoV:1.23 × 10−1) and estimated in different distances away (300–1000 m) (RoV:2.87 × 10−2- 2.75 × 10−2 and NoV:1.14 × 10−1-1.13 × 10−1) were markedly higher than the threshold values recommended by US EPA (10−4 DALY pppy) and WHO (10−6 DALY pppy). The sensitivity analysis highlighted dose exposure and disease burden per case (DBPC) as two most influential factors for both workers and residents following exposure to two pathogens of concern. Due to high resistance and high concentration in the environment, the presence of RoV and NoV can intensify the consequences of diarrhea especially for children under five years of age; A comprehensible and transparent presentation of DALYs and QMRA can help decision makers and responsibilities to justify the priorities of exposure to wastewater in comparison with other risks of daily life.

Leishmania RNA virus (LRV) was first detected in members of the subgenus Leishmania (Viannia), and later, the virulence and metastasis of the New World species were attributed to this virus. The data on the presence of LRV in Old World species are confined to Leishmania major and a few Leishmania aethiopica isolates. The aim of this study was to survey the presence of LRV in various Iranian Leishmania species originating from patients and animal reservoir hosts. Genomic nucleic acids were extracted from 50 cultured isolates belonging to the species Leishmania major, Leishmania tropica, and Leishmania infantum. A partial sequence of the viral RNA-dependent RNA polymerase (RdRp) gene was amplified, sequenced and compared with appropriate sequences from the GenBank database. We detected the virus in two parasite specimens: an isolate of L. infantum derived from a visceral leishmaniasis (VL) patient who was unresponsive to meglumine antimoniate treatment, and an L. major isolate originating from a great gerbil, Rhombomys opimus. The Iranian LRV sequences showed the highest similarities to an Old World L. major LRV2 and were genetically distant from LRV1 isolates detected in New World Leishmania parasites. We could not attribute treatment failure in VL patient to the presence of LRV due to the limited number of specimens analyzed. Further studies with inclusion of more clinical samples are required to elucidate the potential role of LRVs in pathogenesis or treatment failure of Old World leishmaniasis.

ObjectivesThis study aimed to evaluate the specificity, sensitivity, cost, and turn-around time of three methods of gene polymorphism analysis and to study the relationship between IL28B rs12979860 and SVR rate to pegIFN-α/RVB therapy among patients with chronic hepatitis C.MethodsA total of 100 samples from chronic hepatitis C patients were analyzed in parallel using the three methods: direct sequencing, real-time polymerase chain reaction (PCR), amplification refractory mutation system (ARMS)-PCR.ResultsThe different profiles for IL28B rs12979860 alleles (CC, CT, and TT) obtained with PCR-RFLP, ARMS-PCR, and direct sequencing were consistent among the three methods. Prevalence of rs12979860 genotypes CC, CT and TT in HCV genotype 1a was 10(19.6%), 35(68.6%), and six (11.8%), respectively, and in HCV genotype 31, it was 13(26.5%), 31(63.3%), and five (10.2%), respectively. No significant difference was seen between rs12979860 genotype and HCV genotype (p = 0.710).ConclusionScreening by ARMS – PCR SNOP detection represents the most efficient and reliable method to determine HCV polymorphisms in routine clinical practice.

Introduction: Glycoprotein B (gB) is the major antigen for induction of humoral responses against human cytomegalovirus (HCMV) making it an attractive candidate for immune prophylaxis. In the present study, the humoral immune response of BALB/c mice to a truncated HCMV gB protein fused with GFP was evaluated. Methods: The truncated gB coding sequence was synthesized and cloned in pEGFPN1 eukaryotic expression vector and expressed in HEK 293T cell line. After optimization, expression of the recombinant truncated HCMV gB was verified using HRP-conjugated polyclonal antibody specific for HCMV gB.The level of humoral immune responses was assessed in mice using DNA/DNA, peptide/peptide, and DNA/ peptide (prime-boost) immunization strategies. Results: Cloning of the truncated gB coding sequence in the pEGFPN1 was verified by restriction enzyme analysis and sequencing. After optimizing the transfection procedure the number of the GFP positive cells reached 32%. Western blot analysis confirmed the in vitro expression of the truncated HCMV gB protein with an apparent molecular weight of approximately 70 kDa. In vivo prime-boost immunization using HCMV gB DNA/peptide regimen showed significantly higher humoral immune responses compared to the control groups. Conclusion: This study demonstrated that the pEGFPN1 eukaryotic expression vector could be used to optimize and evaluate the expression of this truncated protein.The results also showed that the DNA/peptide vaccination could induce a significant antibody response in animal model.

The presence of hepatitis B virus (HBV) DNA in the absence of traceable hepatitis B surface antigen (HBsAg) in the plasma specimen of patients is defined as occult HBV infection (OBI). This study aimed to detect HBV-DNA in the plasma and peripheral blood mononuclear cells (PBMCs) of Iranian HBsAg negative patients with human immunodeficiency virus (HIV) infection. This cross-sectional study was conducted on 172 patients with HIV infection from September 2015 to August 2017. The patients were tested for serological parameters (HBsAg, HBcAb, HBeAg and HBeAb) against HBV infection. Moreover, they were tested for HBV viral load (using COBAS TaqMan 48 Kit, Roche, USA) in plasma and the presence of the HBV genome in PBMC specimens using real-time PCR. The mean age of the patients was 35.4 ± 13.4 years. Of the 172 studied patients, 109 (63.4%) were male. In this study, 151 (87.8%) patients were negative for HBsAg, 111 (64.5%) patients were negative for all HBV infection serological markers, 9 (5.2%) patients were only positive for HBsAg and 29 (16.9%) patients were only positive for HBcAb. Moreover, five (3.3%) patients with HBsAg negative had OBI (in the plasma sample of four patients and PBMC specimens of all five patients, HBV-DNA was detected). The present study revealed that 3.3% of the patients with HIV infection had occult HBV infection. Presumably, designing prospective studies to identify this infection in patients with HIV infection is informative and valuable.

Background and Aims: Several studies have shown that there is greater number of viruses in deep periodontal pockets than in normal gingival sulcus. We also know that virus may have an important role in induction of Il-1β secretion by different human cells. In this study we intended to determine the capacity of Herpes simplex virus type 1 to stimulate Il-1β secretion in human gingival keratinocytes. Materials and Methods: primary gingival keratinocytes were obtained from samples extracted during crown lengthening surgical procedure. The cells were cultured in 24 well flasks and stimulated by one of these stimulants: LPS, HSV1, LPS+HSV1 and LPS+ATP. After incubation and collecting the supernatants, the amount of secreted Il-1β was measured by ELISA technique. Results: none of the stimulants were able to cause significant amount of Il-1β secretion in any of the incubation times. Conclusion: It seems that HSV1 does not have the capacity to induct IL-1β secretion as a single factor alone or in combination with bacterial LPS.

Aim of the study Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease, which can be lethal with chronic complications. Viral infections may be associated with IPF and other fibrotic lung diseases. In the present study, we investigate for the first time in Iran the related viral etiology of IPF in order to detect three respiratory viruses; human adenovirus, enterovirus and bocavirus. Materials and methods In this cross-sectional study which was supported by Iran University of Medical Sciences, Tehran, Iran. The diagnostic criteria for IPF were based on internationally accepted clinical and imaging criteria in accordance with the 2011 IPF guidelines. 30 nasopharyngeal (NP) swabs or broncho-alveolar lavage (BAL) samples were obtained from the lung of IPF patients that were diagnosed by a sophisticated practitioner from April 2015 to February 2016. Real-time (RT) polymerase chain reaction (PCR) method was performed to detect the three viruses. Fluorescence dye of a labeled probe recorded the results in order to create positive and negative controls. SPSS version 20 software was used to calculate basic descriptive and frequency features. Results Of 30 specimens, 13 (43.4%) were male and 17 (56.6%) were female with the total mean age ± standard deviation 68.2 ± 12.0. RT-PCR assay results illustrated there was no infection of human adenovirus, enterovirus, and bocavirus detected in these samples. Significant results between IPF incidence and variables were not significant ( p > 0.05). Conclusion The causes of IPF in Iranian patients need more research although, based on the results of this study, there was no association between human adenovirus, enterovirus, bocavirus, and IPF.

Background and Objectives: The viruses are the most common cause of eye infection. The most common viruses in conjunctivitis infection include Herpes simplex virus, Adeno virus and Entrovirus. It has been estimated that HSV1 causes 60-90% conjunctival infectionsin adults. Recurrent infection by HSV1 results in Herpes keratitis that is the most common cause for blindness in developing countries. Therefore, a prompt laboratory diagnosis is often very useful. Theaim of this study was to evaluate the prevalence of conjunctivitis infection by HSV-1 Hospital affiliated to Iran University of Medical Sciences (IUMS) in 2009.Methods: This descriptive cross-sectional study was doneon 100 tear film and eye swabs specimens from patient with symptoms of viral conjunctivitis. All samples werecollected in viral transport media (VTM) and inoculated in Vero cell line. Viral cytopatic effect was compared with control sample. HSV1 DNA wasdetected by polymerase chain reaction (PCR). Chi-square test was used to for data analysis (p

Objective: Viral interference has been demonstrated in different systems, such as the effect of enterovirus infection on live-attenuated oral polio vaccine. In this study, the effect of reovirus which could exist in the human intestinal tract on poliovirus vaccine strains was investigated and could be an important factor to consider in oral polio vaccination. Methods: Cells were infected with reovirus, then superinfected with poliovirus. The amount of viral yields was measured by the TCID50 and plaque assay methods. Polioviral RNA synthesis was studied by real-time RT-PCR and the viral RNA load was calculated. Viral protein synthesis was determined using the techniques of immunoflourescent staining and PAGE followed by the immunoblotting experiment. Results: Poliovirus superinfection of reovirus-infected cells resulted in inhibition of poliovirus replication. It was found that the inhibitory effect of reovirus was after establishment of its infection (2 h postinfection). There was no competition between the two viruses for cell attachment but poliovirus RNA and protein synthesis were inhibited. Conclusion: Infection of cells with reovirus could interfere with the growth of poliovirus upon superinfection. This phenomenon could be important to consider when using attenuated poliovirus vaccine.

Background and Aims: Respiratory syncytial virus (RSV) infection is common in infants and young children. In infants younger than one year old it may cause bronchiolitis and pneumonia which requires hospitalization. Accurate and rapid diagnosis of the disease will help proper treatment of the disease and prevents further complications. Methods: Specimen taken from respiratory tract of sick children were processed and fixed for immunofluorescence staining. Monoclonal antibody conjugate specific for RSV was used and the specimens were examined by a UV microscope. Results: A total of 132 samples examined, 40.1% were positive for RSV. The disease was mostly in children less than 6 months old. It occurred mainly during the winter months and there were no significant differences between the male and female children. Conclusion: RSV infects many infants and children annually during the winter. The virus probably infects considerable number of children across Iran. Proper diagnosis of the disease will help in treatment and control of the disease.

Background and Aims: Inhibition of viral growth in coinfected cells with two different viruses has been described. This phenomenon known as viral interference can occur in several virus host systems such as interference of enterovirus infection on poliovirus vaccine strains. In this study we superinfected reovirus infected HeLa cells with poliovirus to determine if poliovirus can replicate in such cells and form mature virus particles. Methods: Cells were infected first with reovirus then were reinfected with poliovirus. The amounts of viral particles were measured by electron microscopy and plaque assay titration. The amount of viral yield was also measured using the technique of real time RT-PCR for measuring the viral load in infected cells. Results: In cells infected first with reovirus and then superinfected with polio virus, only reovirus particles were produced. Virus production was determined by assaying viral titer using the plaque assay technique and electron microscopy. There was no poliovirus particles observable in the superinfected cells. The amount of poliovirus load in reovirus infected cells was also drastically reduced. Conclusion: The growth of poliovirus was inhibited in reovirus infected cells and no infectious poliovirus particles could be observed. This observation could be important to consider in poliovirus vaccination program.

Background: Hepatitis B virus (HBV) has been classified into ten genotypes (A-J) based on genome sequence divergence, which is very important for etiological and clinical investigations. HBV genotypes have distinct geographical distributions worldwide. Objectives: The aim of this study was to investigate the distribution of HBV genotypes among Azerbaijani patients with chronic hepatitis B, came from the Republic of Azerbaijan country to Iran to receive medical care. Patients and Methods: One hundred and three patients with chronic HBV infection, referred to hospitals related to Iran University of Medical Sciences and Tehran Hepatitis Center from August 2011 to July 2014, were enrolled in this cross sectional study. About 3-milliliter of peripheral blood was taken from each patient. After viral DNA extraction, HBV genotypes were tested using the INNO-LiPA™ HBV kit (Innogenetics, Ghent, Belgium). HBV genotyping was confirmed using sequencing of hepatitis B surface antigen (HBsAg) and polymerase (pol) regions of HBV. Results: The mean age of patients was 35.9 ± 11.7 years (19-66). Of 103 patients, 72 (69.9%) were male. In the present study, the predominant HBV genotype was D (93.2%) followed by genotype A (5.8%) and concurrent infection with A and D genotypes (0.97%). Conclusions: The main and frequent HBV genotype among Azerbaijani patients with chronic hepatitis B virus infection was genotype D followed by genotype A.

Background: Wide distribution and low half-life of acyclovir has led to a high dose consumption of the drug. Recent studies have shown that encapsulation of acyclovir in nano-carriers can increase effectiveness and decrease its side effects. We investigated the inhibitory effect of acyclovir loaded nano-niosomes against herpes simplex virus type-1 (HSV-1) in cell culture. Methods: In-vitro cytotoxicity study of empty niosomes (E-N), acyclovir loaded niosomes (ACV-N) and ACV as a free drug against HeLa cell line was performed by MTT assay and the viral titers was tested by TCID50 assay. Results: The results indicated that a significant higher antiviral activity for acyclovir loaded nano-niosomes of about 3 times in comparison with free drug. Conclusion: The results of this study revealed ACV-N have a higher antiviral activity compared with free drug; it could be a suitable carrier for delivery of acyclovir in the treatment of HSV-1 infections.

Currently, there are about 37 million people worldwide living with human immunodeficiency virus (HIV) /AIDS, with an estimated two million new cases per year globally. According to estimates from the World Health Organization (WHO), only 75% of the population with HIV know their status. Initially, HIV infection was associated with significantly increased rates of mortality and morbidity. However, the rapid advances in treatment and the advent of different classes of antiretroviral drugs over time have led to change the face of HIV/AIDS from a deadly infection to chronic and manageable disease. There is strong evidence that HIV-infected patients undergoing antiretroviral therapy have longer lives and are less likely to transmit infection to their sexual partners. Since the introduction of zidovudine in 1987 as the first antiretroviral drug, significant strides have been made in antiretroviral therapy. The introduction of potent antiretroviral drugs for the treatment of HIV infection has been one of the significant events in the evolution of modern medicine. Antiretroviral therapy refers to the use of drugs in the treatment of HIV. Generally, these drugs are categorized based on the steps of the HIV life cycle suppressed by them. There are six main classes of antiretroviral agents including nucleoside/ nucleotide reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, fusion inhibitors, co-receptor inhibitors, and integrase inhibitors. Combination antiretroviral therapy should be considered for HIV patients to achieve the highest viral suppression rate, and to reduce the risk of resistance development and morbidity and mortality associated with AIDS. Achieving and maintaining HIV viral load suppression among treated patients has remarkably increased over the last years due to the development of potent and well-tolerated agents which can be co-formulated as a once-daily single-tablet or fixed-dose combination for simplification. However, there are some limitations preventing patients to benefit from this treatment. The main goals of HIV therapy in the future are to overcome the limitations of current treatment, including side effects. This review will provide an overview of advances in the current antiretroviral drugs by focusing on their pharmacokinetics, mechanism of action, dosing recommendations, and adverse events for each drug class.