Evaluating the therapeutic efficacy of triptolide and (S)-10-hydroxycamptothecin on cutaneous and ocular Herpes Simplex Virus type-1 infections in mice.

Objective: The emergence of Acyclovir-Resistant Herpes Simplex Virus type-1, which is the result of clinical over usage calls for the urgent need of a novel anti-HSV agent. Hence, the activity of Triptolide (TP) and (S)-10-Hydroxycamptothecin (10-HCPT) were investigated as natural products in two infection models of HSV-1. Methods: The antiviral efficacy of TP and 10-HCPT was evaluated in mice ocular and cutaneous infection models of HSV. Groups of 10 mice were infected with HSV-1. Both compounds were administered topically on corneal and skin. The disease severity, viral titer (plaque reduction assay), and histopathology were evaluated in the ocular and cutaneous models of HSV-1 infection on days 3, 5, 7, 9, and 12 post infection, as well as genome loads on days 3 and 12. Results: Topical treatment of corneal with TP, 10-HCPT, and ACV was effective in reducing stromal disease (after day 3, P = 0.001), plus TP and ACV on vascularization (after day 7, P = 0.001). The virus titer decreased significantly in the infected treated groups after day 3 (P < 0.05). Also, on day 12 post-infection, the virus genome volume in the TP and ACV groups was significantly reduced. With respect to virus titers and the DNA yield, significant difference was observed, merely in the ACV group in comparison to the control (P = 0.013). Immunohistochemistry analysis showed that corneal epithelium healing was partially visible in the 10-HCPT group, which gradually increased in TP, and was the highest in the ACV group. The skin epithelium healing was only observed in TP and ACV groups, and was superior in the ACV group. Conclusions: This study revealed the virologic and clinical potential of TP in-vivo to treat ocular mouse model.

Antiviral activity of triptolide on herpes simplex virus in vitro.

BACKGROUND: Herpes simplex virus-type 1 (HSV-1) can cause diseases, especially amongst neonates and immunocompromised hosts. Hence, developing a novel anti-HSV-1 drug with low-level toxicity is vital. Triptolide (TP), a diterpenoid triepoxide is a natural product with range of bioactivity qualities. METHODS: In this study, viral infection was assessed in different phases of the HSV-1 replication cycle on A549 cells, using various assays, such as adsorption inhibition assay, penetration inhibition assay, time-of-addition assay, and quantitative polymerase chain reaction (qPCR). RESULTS: The results indicate that TP can effectively inhibit HSV-1 infection in the lowest range of concentration. TP exhibited significant inhibitory effect on HSV-1 plaque formation, with 50% effective concentration (EC50) of 0.05 µM. Furthermore, the time-of-addition assay suggests that TP has viral inhibitory effects when it was added less than 8 h postinfection (h.p.i.). This result is further confirmed by decline in the expression viral immediate-early genes (ICP4, ICP22, and ICP27) in 6 h.p.i in the TP-treated group compared to the control group, evaluated by real-time qPCR. The Western blotting result was also consistent with the previous findings, which confirms that TP can positively affect ICP4 during HSV-1 infection. CONCLUSIONS: The TP also showed antiviral activity against HSV-1. This dose-dependent activity is an indication of a particular cellular component, rather than cytotoxicity that has mediated its function. Finally, the result suggest a new approach for an effective treatment option of the HSV-1 infections.

Hepatitis C virus genotypes in patients with chronic hepatitis C infection in southern Iran from 2016 to 2019.

Hepatitis C is a liver disease caused by the hepatitis C virus (HCV). The treatment of HCV infection has become more complicated due to various genotypes and subtypes of HCV. The treatment of HCV has made significant advances with direct-acting antivirals. However, for the choice of medicine or the combination of drugs for hepatitis C, it is imperative to detect and discriminate the crucial HCV genotypes. The main objective of this study was to determine the pattern of circulating HCV genotypes in southern Iran, from 2016 until 2019. The other aim of the study was to determine possible associations of patients' risk factors with HCV genotypes. A total of 803 serum samples were collected in 4 years (2016-2019) from patients with HCV antibody positive results. A total of 728 serum samples were HCV-RNA positive. The prevalence of HCV genotypes was detected using the genotype-specific RT-PCR test for serum samples obtained from 615 patients. The HCV genotype 1 (G1) was the most prevalent (48.8%) genotype in the area, with G1a, G1b, and mixed G1a/b representing 38.4%, 10.1%, and 0.3%, respectively. Genotype 3a was the next most prevalent (47.2%). Mixed genotypes 1a/3a were detected in 22 (3.6%) and finally G4 was found in 3 (0.5%) patients. The other HCV genotypes were not detected in any patient. Genotype 1 (1a and 1b alone, 1a/1b and 1a/3a coinfections) is the most prevalent HCV genotype in southern Iran. HCV G1 shows a significantly higher rate in people under 40 years old.

Seroprevalence of viral hepatitis A, B, C, D and E viruses in the Hormozgan province southern Iran.

BACKGROUND: Viral hepatitis is a global public health problem affecting millions of people worldwide, causing thousands of deaths due to acute and persistent infection, cirrhosis, and liver cancer. Providing updated serologic data can improve both surveillance and disease control programs. This study is aimed to determine the seroprevalence of markers for viral hepatitis (A, B, C, D and E) and the epidemiology of such infections in the general population of southern Iran's Hormozgan province. METHODS: Between 2016 and 2017, a total of 562 individuals with ages ranging from 1 to 86 years, who visited governmental public laboratories for routine check-ups, were tested for the presence of serological markers to hepatitis virus types A to E using enzyme-linked immunosorbent assays. RESULTS: The overall anti-hepatitis A virus (HAV) antibody seroprevalence was 93.2% (524/562). The prevalence of anti-hepatitis E virus (HEV) antibodies was 15.8% (89/562) among which 1.6% (9/562) of the seropositive individuals also had evidence of recent exposure to the virus (IgM positivity). Two and a half percent (14/562) were positive for hepatitis B surface (HBs) antigen, whereas 11.6% (65/562) tested positive for anti-hepatitis B core (HBc) antibodies. Among anti-HBc positive patients, 11% (7/65) had HBs Ag and 5% (3/65) were positive for anti-hepatitis D virus (HDV) antibodies. The prevalence of anti-hepatitis C virus (HCV) antibodies was 0.7% (4/562). The seroprevalence of anti-HAV, HEV IgG, anti-HBc antibodies, and HBs Ag increased with age. CONCLUSION: The present study confirms a high seroprevalence of HAV infection among the examined population and reveals high levels of endemicity for HEV in the region. Planned vaccination policies against HAV should be considered in all parts of Iran. In addition, improvements on public sanitation and hygiene management of drinking water sources for the studied area are recommended.

Widespread circulation of West Nile virus, but not Zika virus in southern Iran.

West Nile virus (WNV) and Zika virus (ZIKV) are mosquito-borne viral infections. Over the past few decades, WNV has been associated with several outbreaks involving high numbers of neuroinvasive diseases among humans. The recent re-emergence of ZIKV has been associated with congenital malformation and also with Guillain-Barre syndrome in adults. The geographic range of arthropod-borne viruses has been rapidly increasing in recent years. The objectives of this study were to determine the presence of IgG specific antibodies and the genome of WNV and ZIKV in human samples, as well as WNV and ZIKV genomes in wild-caught mosquitoes in urban and rural areas of the Hormozgan province, in southern Iran. A total of 494 serum samples were tested for the presence of WNV and ZIKV IgG antibodies using ELISA assays. One hundred and two (20.6%) samples were reactive for WNV IgG antibodies. All serum samples were negative for ZIKV IgG antibodies. Using the multivariable logistic analysis, age (45+ vs. 1-25; OR = 3.4, 95% C.I.: 1.8-6.3), occupation (mostly outdoor vs. mostly indoor; OR = 2.4, 95% C.I.: 1.1-5.2), and skin type(type I/II vs. type III/IV and type V/VI; OR = 4.3, 95% C.I.: 1.7-10.8 and OR = 2.7, 95% C.I.: 1.3-5.5 respectively, skin types based on Fitzpatrick scale) showed significant association with WNV seroreactivity. We collected 2,015 mosquitoes in 136 pools belonging to 5 genera and 14 species. Three pools of Culex pipiens complex were positive for WNV RNA using real-time reverse transcription polymerase chain reaction (rtRT-PCR). ZIKV RNA was not detected in any of the pools. All WNV ELISA reactive serum samples were negative for WNV RNA. In conclusion, we provided evidence of the establishment of WNV in southern Iran and no proof of ZIKV in serum samples or in mosquito vectors. The establishment of an organized arbovirus surveillance system and active case finding strategies seems to be necessary.