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Antiviral Research (v.85, #2)
A new tool linking human cytomegalovirus drug resistance mutations to resistance phenotypes by Meike Chevillotte; Jens von Einem; Benjamin M. Meier; Feng-Mao Lin; Hans A. Kestler; Thomas Mertens (pp. 318-327).
Drug resistant strains of human cytomegalovirus (HCMV) in patients at risk may increasingly develop into a problem in the clinical setting. Genotypic resistance testing is becoming the method of choice, but requires previous phenotypic characterisation of each newly found mutation. In order to facilitate the interpretation of the patient's CMV sequence data, a web-based search tool was generated that links the sequence to a database containing all published UL97 (protein kinase) and UL54 (DNA polymerase) mutations and corresponding antiviral drug susceptibility phenotypes. It is reasonable to assume that HCMV drug resistance testing will provide relevant data for an adjustment of therapy and on prognosis of clinical outcome. HCMV drug susceptibility testing will become even more important once new drugs will be available for therapy allowing a wider choice of antiviral agents to treat HCMV disease. These topics will also play a pivotal role for optimising antiviral therapy of HCMV- and other viral diseases.
Keywords: UL97; UL54; Genotype; Clinical outcome; HCMV; GCV; CDV; FOS
Present and future arboviral threats by Scott C. Weaver; William K. Reisen (pp. 328-345).
Arthropod-borne viruses (arboviruses) are important causes of human disease nearly worldwide. All arboviruses circulate among wild animals, and many cause disease after spillover transmission to humans and agriculturally important domestic animals that are incidental or dead-end hosts. Viruses such as dengue (DENV) and chikungunya (CHIKV) that have lost the requirement for enzootic amplification now produce extensive epidemics in tropical urban centers. Many arboviruses recently have increased in importance as human and veterinary pathogens using a variety of mechanisms.Beginning in 1999, West Nile virus (WNV) underwent a dramatic geographic expansion into the Americas. High amplification associated with avian virulence coupled with adaptation for replication at higher temperatures in mosquito vectors, has caused the largest epidemic of arboviral encephalitis ever reported in the Americas. Japanese encephalitis virus (JEV), the most frequent arboviral cause of encephalitis worldwide, has spread throughout most of Asia and as far south as Australia from its putative origin in Indonesia and Malaysia. JEV has caused major epidemics as it invaded new areas, often enabled by rice culture and amplification in domesticated swine. Rift Valley fever virus (RVFV), another arbovirus that infects humans after amplification in domesticated animals, undergoes epizootic transmission during wet years following droughts. Warming of the Indian Ocean, linked to the El Niño-Southern Oscillation in the Pacific, leads to heavy rainfall in east Africa inundating surface pools and vertically infected mosquito eggs laid during previous seasons. Like WNV, JEV and RVFV could become epizootic and epidemic in the Americas if introduced unintentionally via commerce or intentionally for nefarious purposes. Climate warming also could facilitate the expansion of the distributions of many arboviruses, as documented for bluetongue viruses (BTV), major pathogens of ruminants. BTV, especially BTV-8, invaded Europe after climate warming and enabled the major midge vector to expand is distribution northward into southern Europe, extending the transmission season and vectorial capacity of local midge species.Perhaps the greatest health risk of arboviral emergence comes from extensive tropical urbanization and the colonization of this expanding habitat by the highly anthropophilic (attracted to humans) mosquito, Aedes aegypti. These factors led to the emergence of permanent endemic cycles of urban DENV and CHIKV, as well as seasonal interhuman transmission of yellow fever virus. The recent invasion into the Americas, Europe and Africa by Aedes albopictus, an important CHIKV and secondary DENV vector, could enhance urban transmission of these viruses in tropical as well as temperate regions. The minimal requirements for sustained endemic arbovirus transmission, adequate human viremia and vector competence of Ae. aegypti and/or Ae. albopictus, may be met by two other viruses with the potential to become major human pathogens: Venezuelan equine encephalitis virus, already an important cause of neurological disease in humans and equids throughout the Americas, and Mayaro virus, a close relative of CHIKV that produces a comparably debilitating arthralgic disease in South America. Further research is needed to understand the potential of these and other arboviruses to emerge in the future, invade new geographic areas, and become important public and veterinary health problems.
Keywords: Arbovirus; Emergence; Epidemic; Flavivirus; Alphavirus; Climate change
Antiviral effect of diammonium glycyrrhizinate and lithium chloride on cell infection by pseudorabies herpesvirus by Xiuwen Sui; Jiechao Yin; Xiaofeng Ren (pp. 346-353).
Diammonium glycyrrhizin (DG), a salt from glycyrrhizinate (GL) that is a major active component of licorice root extract with various pharmacological activities was investigated for its inhibitory effect on pseudorabies virus (PrV) infection. In parallel, lithium chloride (LiCl), a chemical reagent with potential antiviral activity was compared with DG for their inhibitory ability against PrV infection in vitro. Virus plaque-reduction assays, PCR and RT-PCR analysis indicated that both drugs inhibited cell infection by PrV. Moreover, addition of the drugs resulted in fewer apoptotic cells during PrV infection.
Keywords: Diammonium glycyrrhizinate; Lithium chloride; Pseudorabies virus (PrV); Apoptosis
Detection of antiviral resistance and genetic lineage markers in influenza B virus neuraminidase using pyrosequencing by Tiffany G. Sheu; Varough M. Deyde; Rebecca J. Garten; Alexander I. Klimov; Larisa V. Gubareva (pp. 354-360).
We report here the design of a pyrosequencing approach for the detection of molecular markers of resistance to the neuraminidase inhibitors zanamivir and oseltamivir in influenza viruses of type B. Primers were designed to analyze the sequences at eight amino acid positions E119, R152, D198, I222, S250, H274, R371, and G402 (universal A/N2 numbering) in the neuraminidase (NA) which have been previously found to be associated with resistance or reduced susceptibility to oseltamivir and/or zanamivir in the NA inhibition assay. In addition, the designed primers could be utilized to the distinguish between the NAs of influenza B viruses from the two major lineages (Victoria and Yamagata) that have co-circulated globally in recent years, thus providing a valuable tool for virus strain surveillance.
Keywords: Influenza B; Neuraminidase; Resistance; Genetic analysis; Evolution
Long-term efficacy of interferon alpha therapy on hepatitis B viral replication in patients with chronic hepatitis B: A meta-analysis by Yong-Feng Yang; Wei Zhao; Hai-Ming Xia; Yan-Dan Zhong; Ping Huang; Jian Wen (pp. 361-365).
Interferon (IFN) alpha has been used in the treatment of chronic hepatitis B for decades. Beneficial effects including hepatitis B e antigen (HBeAg)/HBV DNA seroclearance have been documented. However, it remains unclear whether interferon has long-term efficacy on inhibiting hepatitis B viral replication. So we conducted a meta-analysis of available literature to assess the evidence obtained on the efficacy of IFN treatment in chronic HBV infection.Seven clinical controlled trials, including 1550 patients and comparing IFN to no treatment, were selected. Data on the incidence of HBV DNA seroclearance, HBeAg seroclearance, and HBsAg seroclearance in IFN treated and untreated patients were extracted from each study. The evaluation of effectiveness was performed with an intention-to-treat (ITT) method. We used the relative risk (RR) and 95% confidence interval (CI) of the main outcomes as the measure of efficacy. Meta-analysis was performed using fixed-effect or random-effect methods, depending on absence or presence of significant heterogeneity. Analyses were performed with STATA version 9.0 and Review Manager Version 4.2.Four studies including the data of HBeAg seroclearance with significant heterogeneity were analyzed by random-effect method; six studies including the data of HBsAg seroclearance without significant heterogeneity were analyzed by fixed-effect method. A different incidence of HBeAg seroclearance and HBsAg seroclearance was observed between treated and untreated patients. The RR of HBeAg seroclearance and HBsAg seroclearance was 0.66 (95% CI: 0.44, 0.99) and 0.28 (95% CI: 0.17, 0.46), respectively.In conclusion, the results of this meta-analysis indicate that IFN increases the incidence of HBeAg seroclearance and HBsAg seroclearance after long-term follow-up of three to seven years.
Keywords: Interferon; Hepatitis B virus; Long-term efficacy; Meta-analysis
Avoiding drug-resistance development by novel approach of combining anti-enteroviral substances against coxsackievirus B1 infection in mice by Ralitsa Vassileva-Pencheva; Angel S. Galabov (pp. 366-372).
Current study presents a novel scheme for combined application of anti-enteroviral substances in coxsackievirus B1 neuroinfection in newborn mice. It consists of a consecutive alternating, not simultaneous, administration of the substances in combination. A triple combination showing good efficacy was selected as a result of a screening of double, triple and quadruple combinations of enteroviral inhibitors. Its effectiveness is expressed in lengthening of the mean survival time and about 50% reduction of mortality rate in infected newborns as compared both to the placebo group, individual compounds used alone every day, and to the same combination applied simultaneously every day. Chronology of alternation of the individual drug administration plays a key role in the efficacy of the combination. Studies of the drug sensitivity of viral brain isolates from mice, treated with the drug combination indicate that virus isolates from the group treated with the alternating combination not only preserve, but even increase their sensitivity to the drugs. MIC50 values of virus isolates from groups treated with monotherapies of the compounds manifested development of drug resistance. Obviously, the consecutive alternating administration of anti-enteroviral substances hinders the occurrence of drug resistance in the course of experimental coxsackievirus B1 infection in mice.
Keywords: Coxsackievirus B1; Combinations; Mice; Resistance; Drug sensitivity
Modulation of cytokine production by 7-hydroxycoumarin in vitro and its efficacy against influenza infection in mice by Masahiko Kurokawa; Wataru Watanabe; Tomomi Shimizu; Rie Sawamura; Kimiyasu Shiraki (pp. 373-380).
We previously demonstrated that 7-hydroxycoumarin (7HC) was effective in reducing proinflammatory cytokine production in lipopolysaccharide-exposed macrophage-like P388D1 cells and fever production by suppressing the increase in interleukin (IL)-1α production in an influenza virus-intranasal infection model in mice. In this study, we assessed the effects of modulation of cytokine production by 7HC on influenza virus infection in relation to its efficacy in influenza virus-infected mice. 7HC was confirmed to suppress proinflammatory cytokine levels in P388D1 cells due to influenza virus infection. In the murine infection model, oral administration of 7HC (30mg/kg) was significantly effective in reducing the weight loss of infected mice and virus titers in the bronchoalveolar lavage fluid (BALF) of lungs and in prolonging survival times without toxicity. The rise of proinflammatory and Th1 cytokine (IL-12 and interferon-γ) production in the BALF from infected mice was significantly suppressed by 7HC at two and four days post-infection, respectively. This suppression correlated with the reduction of virus titers and diminution of lung consolidation. Because 7HC did not exhibit direct anti-influenza virus activity in vitro, 7HC was suggested to suppress pneumonia in influenza virus-infected mice through suppression of the cytokine production induced by infection.
Keywords: Influenza infection; 7-Hydroxycoumarin; Cytokines; Lung; Mouse
Host cell selection of influenza neuraminidase variants: Implications for drug resistance monitoring in A(H1N1) viruses by Margaret Okomo-Adhiambo; Ha T. Nguyen; Katrina Sleeman; Tiffany G. Sheu; Varough M. Deyde; Rebecca J. Garten; Xiyan Xu; Michael W. Shaw; Alexander I. Klimov; Larisa V. Gubareva (pp. 381-388).
The neuraminidase inhibitors (NAIs), oseltamivir and zanamivir, are essential for treatment and prevention of influenza A and B infections. Oseltamivir resistance among influenza A (H1N1) viruses rapidly emerged and spread globally during the 2007–2008 and 2008–2009 influenza seasons. Approximately 20% and 90% of viruses tested for NAI susceptibility at CDC during these seasons, respectively, were resistant to oseltamivir (IC50 ∼100–3000 time>those of sensitive viruses), based on the chemiluminescent NA inhibition assay. Pyrosequencing analysis confirmed H274Y mutation (H275Y in N1 numbering) in the neuraminidase (NA) gene of oseltamivir-resistant viruses. Full NA sequence analysis of a subset of oseltamivir-resistant and sensitive virus isolates from both seasons ( n=725) showed that 53 (7.3%) had mutations at residue D151 (D→E/G/N), while 9 (1.2%) had mutations at Q136 (Q→K) and 2 (0.3%) had mutations at both residues. Viruses with very high IC50 for oseltamivir and peramivir, and elevated IC50 for zanamivir, had H274Y in addition to mutations at D151 and/or Q136, residues which can potentially confer NAI resistance based on recent N1 NA crystal structure data. Mutations at D151 without H274Y, did not elevate IC50 for any tested NAI, however, Q136K alone significantly reduced susceptibility to zanamivir (36-fold), peramivir (80-fold) and A-315675 (114-fold) but not oseltamivir. Mutations at D151 and Q136 were present only in MDCK grown viruses but not in matching original clinical specimens ( n=33) which were available for testing, suggesting that these variants were the result of cell culture selection or they were present in very low proportions. Our findings provide evidence that propagation of influenza virus outside its natural host may lead to selection of virus variants with mutations in the NA that affect sensitivity to NAIs and thus poses implications for drug resistance monitoring and diagnostics.
Keywords: Cell culture; Antiviral resistance; Tamiflu; Relenza; Peramivir; A-315675
Characterization of a thymidine kinase-deficient mutant of equine herpesvirus 4 and in vitro susceptibility of the virus to antiviral agents by Walid Azab; Koji Tsujimura; Kentaro Kato; Jun Arii; Tomomi Morimoto; Yasushi Kawaguchi; Yukinobu Tohya; Tomio Matsumura; Hiroomi Akashi (pp. 389-395).
Equine herpesvirus 4 (EHV-4) is an important equine pathogen that causes respiratory tract disease among horses worldwide. A thymidine kinase (TK)-deletion mutant has been generated by using bacterial artificial chromosome (BAC) technology to investigate the role of TK in pathogenesis. Deletion of TK had virtually no effect on the growth characteristics of WA79ΔTK in cell culture when compared to the parent virus. Also, virus titers and plaque formation were unaffected in the absence of the TK gene. The sensitivity of EHV-4 to inhibition by acyclovir (ACV) and ganciclovir (GCV) was studied by means of a plaque reduction assay. GCV proved to be more potent and showed a superior anti-EHV-4 activity. On the other hand, ACV showed very poor ability to inhibit EHV-4 replication. As predicted, WA79ΔTK was insensitive to GCV. Although EHV-4 is normally insensitive to ACV, it showed >20-fold increase in sensitivity when the equine herpesvirus-1 (EHV-1) TK was supplied in trans. Furthermore, both ACV and GCV resulted in a significant reduction of plaque size induced by EHV-4 and 1. Taken together, these data provided direct evidence that GCV is a potent selective inhibitor of EHV-4 and that the virus-encoded TK is an important determinant of the virus susceptibility to nucleoside analogues.
Keywords: EHV-4; TK; Antiviral drugs
Human leukocyte antigen alleles and the response to pegylated interferon/ribavirin therapy in chronic hepatitis C patients by Chia-Yen Dai; Wan-Long Chuang; Ming-Yen Hsieh; Jee-Fu Huang; Ya-Yun Lin; Pei-Yu Chu; Nai-Jen Hou; Zu-Yau Lin; Shinn-Cherng Chen; Ming-Yuh Hsieh; Liang-Yen Wang; Ming-Lung Yu (pp. 396-402).
Human leukocyte antigens (HLAs) may play a role in the clinical evolution of hepatitis C virus (HCV) infection. The present study was aimed at elucidating the association between the HLA loci and responses to combination therapy with pegylated interferon-alpha 2a (PEG-IFN) and ribavirin in Taiwanese. We enrolled a total of 208 treatment-naïve Taiwanese chronic hepatitis C (CHC) patients treated with combination therapy. Patients with sustained virological response (SVR) had a significantly higher frequency of genotype non-1b infection, lower pretreatment HCV RNA levels and a higher frequency of mild hepatic fibrosis (fibrosis score: F: 0–2). The HLA A24 and B40 alleles were significantly associated with SVR after adjusted for the other three confounding factors including HCV genotype, hepatic fibrosis and pretreatment serum HCV RNA levels. Haplotypes (B40-DRB1*3, B46- DRB1*9, Cw1- DQB1*3, and Cw1- DRB1*9) were significantly associated with SVR to combination therapy. For 167 patients with genotype 1b infection and viral load < or =5.6logIU/ml or genotype non-1b infection, the B46 was significantly associated with sustained response with OR (odds ratio) [95% CI (confidence interval) of 0.047 (0.168–0.988)]. Haplotypes B40-DRB1*3, B46- DRB1*9, Cw1- DQB1*3, Cw1- DRB1*9 and DQB1*3- DRB1*9 were found to be associated with SVR to PEG-IFN/ribavirin therapy with OR (95% CI) of 0.179 (0.032–0.989), 0.313 (0.107–0.918), 0.350 (0.145–0.845), 0.282 (0.105–0.759) and 0.412 (0.174–0.978), respectively. We concluded that the virological and the host immunogenetic factors may possibly predict the response to combination therapy in CHC patients.
Keywords: Hepatitis C virus; Human leukocyte antigen; Pegylated interferon; Ribavirin; Sustained virological response
Similar antiviral efficacy and tolerability between efavirenz and lopinavir/ritonavir, administered with abacavir/lamivudine (Kivexa®), in antiretroviral-naïve patients: A 48-week, multicentre, randomized study (Lake Study) by P. Echeverría; E. Negredo; G. Carosi; J. Gálvez; J.L. Gómez; A. Ocampo; J. Portilla; A. Prieto; J.C. López; R. Rubio; A. Mariño; E. Pedrol; C. Viladés; A. del Arco; A. Moreno; I. Bravo; R. López-Blazquez; N. Pérez-Alvarez; B. Clotet (pp. 403-408).
Although efavirenz and lopinavir/ritonavir(r) are both recommended antiretroviral agents in antiretroviral-naïve HIV-infected patients, there are few randomized comparisons of their efficacy and tolerability.A multicenter and randomized study was performed including 126 antiretroviral-naïve patients, randomly assigned to efavirenz+Kivexa® ( n=63) or lopinavir/r+Kivexa® ( n=63). Efficacy endpoints were the percentage of patients with HIV-RNA ≤50copies/mL at week 48 and CD4 recovery. Safety was assessed by comparing toxicity and discontinuations. Statistical analyses were performed on an intention-to-treat (ITT) basis (Missing=Failure).At week 48, 56.7% of patients in the efavirenz and 63.2% in the lopinavir/r groups showed HIV-1 RNA <50copies/mL ( P=0.770) (intention-to-treat analysis; Missing=Failure). Only 1 (1.53%) patient from each group experienced virological failure. CD4 values increased in both groups (298 cells in the efavirenz group, P=0.001; 249 cells in the lopinavir/r group, P=0.002; P=0.126 between groups). HDL-cholesterol only increased in the efavirenz group (from 39±12mg/dL to 49±11; P=0.001). Discontinuations were more frequent in the lopinavir/r group (36.5% versus 28.5%; P=0.193), but more patients with efavirenz interrupted due to toxicity (11.1% versus 6.3%); most of them were attributed to hypersensitivity reaction.Similar virological efficacy was observed for efavirenz and lopinavir/r, when administered with Kivexa® in antiretroviral-naïve patients, while immunological improvement was slightly superior for efavirenz. The higher rate of discontinuation due to toxicity in the efavirenz group was related to a higher incidence of hypersensitivity reaction. Nowadays, the use of the new formulation of lopinavir/r and the HLA-B*5701 genotype test before starting abacavir should improve the safety profiles of these regimens.
Keywords: Efavirenz; Lopinavir/ritonavir; Kivexa; ®; Randomized study; Efficacy; Tolerability
HIV-1 non-B subtypes: High transmitted NNRTI-resistance in Spain and impaired genotypic resistance interpretation due to variability by G. Yebra; M. de Mulder; J. del Romero; C. Rodríguez; A. Holguín (pp. 409-417).
Genotypic resistance algorithms interpret drug-resistance mutations, but are mainly developed for HIV-1 subtype B, meanwhile non-B subtypes cause 90% of worldwide infections. They include clade-specific amino acid at drug-resistance positions different than subtype B.This study explores: (i) the variability at resistance-related positions in 128 non-B and 226 B sequences from 354 treatment-naïve patients diagnosed in Spain (1999–2007); (ii) the discordances between five resistance interpretation algorithms (ANRS, Stanford, Rega, Geno2pheno, RIS); and (iii) the reliability of five subtyping tools (Stanford, Geno2pheno, Rega, NCBI, EuResist) for each HIV-1 variant.Primary drug-resistance prevalence was 13.6%, although higher in non-B vs. B subtypes (18.7% vs. 10.6%), due to a twofold higher NNRTI-resistance prevalence (15.7% vs. 7.6%). Most secondary PI-resistances, more frequent in non-B, were in fact clade-specific residues. Most sequences were interpreted as susceptible to all antiretrovirals by the five resistance algorithms, except for tipranavir by ANRS in non-B clades. Interalgorithm discordances were significantly higher in non-B variants for specific drugs. The agreement with phylogenetic analysis differed among subtyping tools testing non-B variants.We found a higher prevalence of NNRTI-resistance mutations in non-B subtypes. Certain algorithms overestimate the resistance in non-B subtypes due to natural patterns of mutations. Subtyping tools should be optimised for non-B variants.
Keywords: HIV-1 subtypes; Drug-resistance mutations; Genotypic resistance algorithms; Subtyping tools
Debio-025 inhibits HIV-1 by interfering with an early event in the replication cycle by Dirk Daelemans; Jean-Maurice Dumont; Brigitte Rosenwirth; Erik De Clercq; Christophe Pannecouque (pp. 418-421).
Cyclophilin A is a peptidyl-propyl isomerase that binds the capsid (p24) protein of HIV-1 and facilitates replication. We report a cyclophilin inhibitor, a non-immunosuppressive cyclosporine analogue, Debio-025, that is about 15-times more potent than cyclosporine A and less toxic resulting in a selectivity index of more than 300. It was equally active against virus strains that were resistant toward inhibitors of the viral entry, fusion, or reverse transcription while it was not inhibitory to HIV-2 or SIVMAC. Mechanism of action studies demonstrate that Debio-025 inhibits the HIV-1 replication by interfering with an early stage of the viral replication cycle. Indeed, addition of Debio-025 could be postponed for 2h before loosing its antiviral activity. The compound proved inactive against mutant viruses that are independent of cyclophilin A binding suggesting Debio-025 targets the cyclophilin A–capsid interaction.
Keywords: HIV; Cyclosporine; Cyclophilin; Debio-025; Time-of-addition
In vitro inhibition of the replication of classical swine fever virus by capsid-targeted virus inactivation by Yu-Fei Wang; Zhong-Hua Wang; Yan Li; Xing-Juan Zhang; Yuan Sun; Miao Li; Hua-Ji Qiu (pp. 422-424).
Classical swine fever virus (CSFV) is the causative agent of classical swine fever (CSF), a highly contagious fatal disease of swine. Few effective antiviral drugs are currently available against CSFV infections. To explore the feasibility of using capsid-targeted viral inactivation (CTVI) as an antiviral strategy against CSFV infections, we expressed the CSFV capsid protein (Cap) fused with the nuclease of Staphylococcus aureus (SN) in Escherichia coli and investigated its effects on the replication of CSFV in PK-15 cells. The results indicated that the fusion protein Cap-SN showed a strong Ca2+-dependent nuclease activity and inhibited the replication of CSFV in a dose-dependent manner, with complete inhibition at a concentration of 15μg/ml, whereas the Cap fused with an enzymatically inactive SN (Cap-SN*) showed no nuclease activity or antiviral effects. Thus, the CTVI approach might be applicable to CSFV inhibition as a novel antiviral strategy.
Keywords: Capsid-targeted viral inactivation (CTVI); Classical swine fever virus; Antiviral strategy; Protein transduction domain
Lignan, sesquilignans and dilignans, novel HIV-1 protease and cytopathic effect inhibitors purified from the rhizomes of Saururus chinensis by JiSuk Lee; Myoung Sook Huh; Young Choong Kim; Masao Hattori; Toru Otake (pp. 425-428).
Five lignans were isolated from the ethyl acetate extracts of Saururus chinensis rhizomes and evaluated for anti-HIV-1 activity. Their structures were elucidated as two dilignans, manassantin A (1), manassantin B (2), two sesquilignans, saucerneol B (3) and saucerneol C (4), and a new lignan, saururin B (5) by spectroscopic analysis. Of these components, manassantin A (1) and saururin B (5) showed dose-dependent inhibitory activities on HIV-1 protease with IC50 values of 38.9 and 5.6μM. In addition, manassantins A (1), B (2) and saucerneol B (3) inhibited HIV-1-induced cytopathic effects in a human T lymphoblastoid cell line with IC100 values of 1.0, 1.0 and 0.2μM, respectively. Of these active constituents, saucerneol B (3) showed the most potent and selective anti-HIV-1 activity (IC100 of 0.2μM, CC0 of >125.0μM, and SI of >520.8).
Keywords: Saururus chinensis; Saururin B; Lignan; Sesquilignan; Saucerneol B; Saucerneol C; Dilignan; Manassantins A and B; HIV-1 protease; HIV-1-induced cytopathic effect