A regulatory gap analysis of midwifery to deliver essential reproductive, maternal, newborn, child and adolescent health services in Lao People's Democratic Republic.

Background: In Lao Peoples Democratic Republic, midwives are the main providers of primary reproductive, maternal, newborn, child and adolescent (RMNCAH) services. We analyzed to what extent practice regulations allow midwives to provide nationally defined essential RMNCAH services. Methods: Stakeholder consultations and document reviews were conducted to identify the essential RMNCAH interventions and care tasks midwives are expected to provide without physicians. These were defined in: 1) the Essential Health Service Package (EHSP) and 2) 18 national standards and guidelines. We then mapped whether midwifery regulations, which provide the legal framework for clinical service provision, supported delivery of these standards to identify regulatory gaps. Data were used to update regulations. Findings: Midwives were expected to provide 39 RMNCAH interventions without physicians, representing 1100 care tasks. Midwifery practice regulations allowed eight of 39 interventions (20.5%) and 705 of 1100 care tasks (64.1%) at baseline. Of the 31 interventions not allowed for provision by midwives, 83.9% (26) required prescribing and giving medicines, 51.6% (16) ordering and conducting diagnostics, 38.7% (12) making a clinical diagnosis, and 22.6% (7) use of non-pharmacological interventions. The Ministry of Health convened a multi-stakeholder group to revise the midwifery practice regulations, which increased the legally supported interventions and care tasks to 37 (94.9%) and 1081 (98.3%), respectively. Interpretation: This novel methodology enabled systematic identification and quantification of regulatory gaps in midwifery practice and data-driven revisions. Consequently, regulatory support for delivery of primary RMNCAH interventions vastly improved. The approach can be applied to other clinical cadres, service areas and countries. Funding: Korea Foundation for International Health Care (KOFIH) supported research operation.

A gap analysis of midwifery competency, pre- and in-service education for reproductive, maternal, newborn, child and, adolescent health in Lao People's Democratic Republic.

Background: Ensuring midwives deliver quality essential services requires systematic and timely updates to midwifery education based on constantly evolving global evidence and local needs. However, midwifery curricula are often not updated to incorporate new evidence, consistent with national standards. This study supported the Ministry of Health of Lao People's Democratic Republic to identify gaps in the midwifery competency framework and training packages. Methods: Stakeholder consultations and a document review were conducted to define a core package of RMNCAH interventions and care tasks that midwives should provide based on the national Essential Health Service Package (EHSP). Nationally defined midwifery competencies, the higher diploma midwifery curriculum, and in-service training packages were mapped against required interventions and care tasks. Data were used to revise midwifery education standards. Findings: Midwives were expected to provide 47 RMNCAH interventions based on the EHSP. At baseline, 7 (14.9%), 11 (23.4%) and 35 (74.5%) of the 47 interventions were included in the midwifery competency, higher diploma in midwifery curriculum, and in-service training materials, respectively. After revision, the midwifery competency framework included 42 of 47 interventions (89.4%). The data are currently being used to review and update the national midwifery pre-service diploma curriculum. Interpretation: This analysis enabled the Ministry to identify RMNCAH content gaps in national midwifery education standards and align them with the EHSP. Regular use of a quantitative approach to review educational content is essential to ensure standards are consistent with changing evidence. The approach has potential application to other service areas, cadres, and countries. Funding: Korea Foundation for International Healthcare (KOFIH) supported research operation.

Bisphenol A (BPA) and Cardiovascular or Cardiometabolic Diseases.

Bisphenol A (BPA; 4,4'-isopropylidenediphenol) is a well-known endocrine disruptor. Most human exposure to BPA occurs through the consumption of BPA-contaminated foods. Cardiovascular or cardiometabolic diseases such as diabetes, obesity, hypertension, acute kidney disease, chronic kidney disease, and heart failure are the leading causes of death worldwide. Positive associations have been reported between blood or urinary BPA levels and cardiovascular or cardiometabolic diseases. BPA also induces disorders or dysfunctions in the tissues associated with these diseases through various cell signaling pathways. This review highlights the literature elucidating the relationship between BPA and various cardiovascular or cardiometabolic diseases and the potential mechanisms underlying BPA-mediated disorders or dysfunctions in tissues such as blood vessels, skeletal muscle, adipose tissue, liver, pancreas, kidney, and heart that are associated with these diseases.

Synthesis, Odour Characteristics, and Antimicrobial Activity of Optically Active (Z)-7-Decen-4-olide and Its Derivatives.

Six optically active (Z)-7-decen-4-olide derivatives (1a-1f) were synthesized in 99% enantiomeric excess using diastereomeric resolution. The odour properties of the racemic and optically active 1a-1f were evaluated in terms of their orthonasal aromas. All of the stereoisomers had different odour characteristics and thresholds. Decen-4-olides (1a-1c) had a strong fruity note, whereas undecen-4-olide (1d and 1e) and dodecen-4-olide (1f) had a strong green note. For 7-alken-4-olides (1a, 1d, and 1f), the (R)-enantiomer had a lower odour threshold than the (S)-enantiomer. In contrast, no difference in the odour threshold was observed for the enantiomers of the 8-alken-4-olides (1b and 1e). Furthermore, the antimicrobial activity against Escherichia coli (E. coli; ATCC 25922) and Staphylococcus aureus (S. aureus; ATCC 29213) were investigated. Although the no differences in the antimicrobial activity of the stereoisomers was observed, 1d and 1e showed slight antimicrobial activity against E. coli, whereas only 1f showed antimicrobial activity against S. aureus. No antimicrobial activity was exhibited by (R)-1f, whereas (S)-1f exhibited strong antimicrobial activity.

Time-course changes in mental distress and their predictors in response to the coronavirus disease 2019 (COVID-19) pandemic: A longitudinal multi-site study of hospital staff.

The coronavirus disease 2019 (COVID-19) pandemic provides a unique opportunity studying individual differences in the trajectory of mental distress to relatively homogeneous stressors by longitudinally examining time-course changes between pandemic waves. For 21 months, we tested the effects of COVID-19 waves on mental health among 545 staffs at 18 hospitals treating COVID-19 patients in Shizuoka Prefecture, Japan. Contrary to increasing new infected cases as waves progressed, initially elevated psychological distress (K6) and fear of COVID-19 (FCV-19S) were decreased among waves (K6: B = -.02, 95% confidence interval [CI] = -.03 to -.01; FCV-19S: B = -.10, 95% CI = -.16 to -.04). This initial increase and subsequent decrease in K6 and FCV-19S were more prominent in individuals with high trait anxiety (K6: B = 1.55, 95% CI = 1.18 to 1.91; FCV-19S: B = 4.27, 95% CI = 2.50 to 6.04) and in occupations other than physicians or nurses. The current study revealed time-course changes in psychological distress and fear regarding COVID-19 in each pandemic wave and across waves, and indicated the usefulness of trait anxiety and occupation as predictors of mental health outcomes.

Quality of routine health data at the onset of the COVID-19 pandemic in Ethiopia, Haiti, Laos, Nepal, and South Africa.

BACKGROUND: During the COVID-19 pandemic, governments and researchers have used routine health data to estimate potential declines in the delivery and uptake of essential health services. This research relies on the data being high quality and, crucially, on the data quality not changing because of the pandemic. In this paper, we investigated those assumptions and assessed data quality before and during COVID-19. METHODS: We obtained routine health data from the DHIS2 platforms in Ethiopia, Haiti, Lao People's Democratic Republic, Nepal, and South Africa (KwaZulu-Natal province) for a range of 40 indicators on essential health services and institutional deaths. We extracted data over 24 months (January 2019-December 2020) including pre-pandemic data and the first 9 months of the pandemic. We assessed four dimensions of data quality: reporting completeness, presence of outliers, internal consistency, and external consistency. RESULTS: We found high reporting completeness across countries and services and few declines in reporting at the onset of the pandemic. Positive outliers represented fewer than 1% of facility-month observations across services. Assessment of internal consistency across vaccine indicators found similar reporting of vaccines in all countries. Comparing cesarean section rates in the HMIS to those from population-representative surveys, we found high external consistency in all countries analyzed. CONCLUSIONS: While efforts remain to improve the quality of these data, our results show that several indicators in the HMIS can be reliably used to monitor service provision over time in these five countries.

Associations between the stringency of COVID-19 containment policies and health service disruptions in 10 countries.

BACKGROUND: Disruptions in essential health services during the COVID-19 pandemic have been reported in several countries. Yet, patterns in health service disruption according to country responses remain unclear. In this paper, we investigate associations between the stringency of COVID-19 containment policies and disruptions in 31 health services in 10 low- middle- and high-income countries in 2020. METHODS: Using routine health information systems and administrative data from 10 countries (Chile, Ethiopia, Ghana, Haiti, Lao People's Democratic Republic, Mexico, Nepal, South Africa, South Korea, and Thailand) we estimated health service disruptions for the period of April to December 2020 by dividing monthly service provision at national levels by the average service provision in the 15 months pre-COVID (January 2019-March 2020). We used the Oxford COVID-19 Government Response Tracker (OxCGRT) index and multi-level linear regression analyses to assess associations between the stringency of restrictions and health service disruptions over nine months. We extended the analysis by examining associations between 11 individual containment or closure policies and health service disruptions. Models were adjusted for COVID caseload, health service category and country GDP and included robust standard errors. FINDINGS: Chronic disease care was among the most affected services. Regression analyses revealed that a 10% increase in the mean stringency index was associated with a 3.3 percentage-point (95% CI -3.9, -2.7) reduction in relative service volumes. Among individual policies, curfews, and the presence of a state of emergency, had the largest coefficients and were associated with 14.1 (95% CI -19.6, 8.7) and 10.7 (95% CI -12.7, -8.7) percentage-point lower relative service volumes, respectively. In contrast, number of COVID-19 cases in 2020 was not associated with health service disruptions in any model. CONCLUSIONS: Although containment policies were crucial in reducing COVID-19 mortality in many contexts, it is important to consider the indirect effects of these restrictions. Strategies to improve the resilience of health systems should be designed to ensure that populations can continue accessing essential health care despite the presence of containment policies during future infectious disease outbreaks.

Electrostatic interaction between sulfated polysaccharides and oligopeptides from viral envelope glycoproteins using surface plasmon resonance.

Biotinylated oligopeptides from the envelope glycoproteins of dengue fever virus, influenza A and B viruses, and human immunodeficiency virus (HIV) were synthesized and their interaction with curdlan and dextran sulfates was investigated using surface plasmon resonance to evaluate the antiviral mechanisms of sulfated polysaccharides. More than two clusters consisting of basic amino acids in the oligopeptides from dengue fever virus, strongly interacted with the sulfated polysaccharides elucidated by the association- and dissociation-rate constants. Interactions decreased with the decreasing molecular weights of the sulfated polysaccharides. Although oligopeptides from influenza A virus potently interacted with the sulfated polysaccharides, no interaction was detected on a B/Hong Kong virus oligopeptide bearing few basic amino acids. For the C terminus and V3 region short and long oligopeptides from HIV gp120, the interaction was enhanced by the number of clustered basic amino acids and was inhibited by acidic and bulky amino acids.

Linear π-conjugated polycyclic compounds consisting of four-, five-, and six-membered rings: benzo[1'',2'':3,4;4'',5'':3',4']bis(cyclobuta[1,2-c]thiophene).

Linear π-conjugated polycyclic compounds, BBCTs, containing linearly annulated 5-, 4-, 6-, 4-, and 5-membered rings were produced via copper-mediated double intramolecular coupling reactions. The absorption spectra and electrochemical results confirmed their moderate optical energy gaps and high HOMO energy levels, respectively. In a crystalline state, the BBCT molecules adopt a herringbone structure, while the methylated molecules form slipped one-dimensional columns. The local and global aromaticity of the new polycyclic compounds is discussed based on the experimental results and theoretical predictions. The present fundamental findings are useful for the further design and synthesis of novel π-conjugated polycyclic compounds containing four-membered rings with potential applications in electronic materials.

Tracking health system performance in times of crisis using routine health data: lessons learned from a multicountry consortium.

COVID-19 has prompted the use of readily available administrative data to track health system performance in times of crisis and to monitor disruptions in essential healthcare services. In this commentary we describe our experience working with these data and lessons learned across countries. Since April 2020, the Quality Evidence for Health System Transformation (QuEST) network has used administrative data and routine health information systems (RHIS) to assess health system performance during COVID-19 in Chile, Ethiopia, Ghana, Haiti, Lao People's Democratic Republic, Mexico, Nepal, South Africa, Republic of Korea and Thailand. We compiled a large set of indicators related to common health conditions for the purpose of multicountry comparisons. The study compiled 73 indicators. A total of 43% of the indicators compiled pertained to reproductive, maternal, newborn and child health (RMNCH). Only 12% of the indicators were related to hypertension, diabetes or cancer care. We also found few indicators related to mental health services and outcomes within these data systems. Moreover, 72% of the indicators compiled were related to volume of services delivered, 18% to health outcomes and only 10% to the quality of processes of care. While several datasets were complete or near-complete censuses of all health facilities in the country, others excluded some facility types or population groups. In some countries, RHIS did not capture services delivered through non-visit or nonconventional care during COVID-19, such as telemedicine. We propose the following recommendations to improve the analysis of administrative and RHIS data to track health system performance in times of crisis: ensure the scope of health conditions covered is aligned with the burden of disease, increase the number of indicators related to quality of care and health outcomes; incorporate data on nonconventional care such as telehealth; continue improving data quality and expand reporting from private sector facilities; move towards collecting patient-level data through electronic health records to facilitate quality-of-care assessment and equity analyses; implement more resilient and standardized health information technologies; reduce delays and loosen restrictions for researchers to access the data; complement routine data with patient-reported data; and employ mixed methods to better understand the underlying causes of service disruptions.

Importance of accessibility to the extracellular juxtamembrane stalk region of membrane protein for substrate recognition by viral ubiquitin ligase K5.

Kaposi's sarcoma-associated herpesvirus (KSHV) is a carcinogenic virus that latently infects B cells and causes malignant tumors in immunocompromised patients. KSHV utilizes two viral E3 ubiquitin ligases, K3 and K5, in KSHV-infected cells to mediate the polyubiquitination-dependent down-regulation of several host membrane proteins involved in the immune system. Although K3 and K5 are members of the same family and have similar structural topologies, K3 and K5 have different substrate specificities. Hence, K5 may have a different substrate recognition mode than K3; however, the molecular basis of substrate recognition remains unclear. Here, we investigated the reason why human CD8α, which is known not to be a substrate for both K3 and K5, is not recognized by them, to obtain an understanding for molecular basis of substrate specificity. CD8α forms a disulfide-linked homodimer under experimental conditions to evaluate the viral ligase-mediated down-regulation. It is known that two interchain disulfide linkages in the stalk region between each CD8α monomer (Cys164-Cys164 and Cys181-Cys181) mediate homodimerization. When the interchain disulfide linkage of Cys181-Cys181 was eliminated, CD8α was down-regulated by K5 with a functional RING variant (RINGv) domain via polyubiquitination at the cytoplasmic tail. Aspartic acid, located at the stalk/transmembrane interface of CD8α, was essential for K5-mediated down-regulation of the CD8α mutant without a Cys181-Cys181 linkage. These results suggest that disulfide linkage near the stalk/transmembrane interface critically inhibits substrate targeting by K5. Accessibility to the extracellular juxtamembrane stalk region of membrane proteins may be important for substrate recognition by the viral ubiquitin ligase K5.

COVID-19 and resilience of healthcare systems in ten countries.

Declines in health service use during the Coronavirus Disease 2019 (COVID-19) pandemic could have important effects on population health. In this study, we used an interrupted time series design to assess the immediate effect of the pandemic on 31 health services in two low-income (Ethiopia and Haiti), six middle-income (Ghana, Lao People's Democratic Republic, Mexico, Nepal, South Africa and Thailand) and high-income (Chile and South Korea) countries. Despite efforts to maintain health services, disruptions of varying magnitude and duration were found in every country, with no clear patterns by country income group or pandemic intensity. Disruptions in health services often preceded COVID-19 waves. Cancer screenings, TB screening and detection and HIV testing were most affected (26-96% declines). Total outpatient visits declined by 9-40% at national levels and remained lower than predicted by the end of 2020. Maternal health services were disrupted in approximately half of the countries, with declines ranging from 5% to 33%. Child vaccinations were disrupted for shorter periods, but we estimate that catch-up campaigns might not have reached all children missed. By contrast, provision of antiretrovirals for HIV was not affected. By the end of 2020, substantial disruptions remained in half of the countries. Preliminary data for 2021 indicate that disruptions likely persisted. Although a portion of the declines observed might result from decreased needs during lockdowns (from fewer infectious illnesses or injuries), a larger share likely reflects a shortfall of health system resilience. Countries must plan to compensate for missed healthcare during the current pandemic and invest in strategies for better health system resilience for future emergencies.

Direct evidence of edge-to-face CH/π interaction for PAR-1 thrombin receptor activation.

Heptapeptide SFLLRNP is a receptor-tethered ligand of protease-activated receptor 1 (PAR-1), and its Phe at position 2 is essential for the aggregation of human platelets. To validate the structural elements of the Phe-phenyl group in receptor activation, we have synthesized a complete set of S/Phe/LLRNP peptides comprising different series of fluorophenylalanine isomers (Fn)Phe, where n = 1, 2, 3, and 5. Phe-2-phenyl was strongly suggested to be involved in the edge-to-face CH/π interaction with the receptor aromatic group. In the present study, to prove this receptor interaction definitively, we synthesized another series of peptide analogs containing (F4)Phe-isomers, with the phenyl group of each isomer possessing only one hydrogen atom at the ortho, meta, or para position. When the peptides were assayed for their platelet aggregation activity, S/(2,3,4,6-F4)Phe/LLRNP and S/(2,3,4,5-F4)Phe/LLRNP exhibited noticeable activity (34% and 6% intensities of the native peptide, respectively), whereas S/(2,3,5,6-F4)Phe/LLRNP was completely inactive. The results indicated that, at the ortho and meta positions but not at the para position, benzene-hydrogen atoms are required for the CH/π interaction to activate the receptor. The results provided a decisive evidence of the molecular recognition property of Phe, the phenyl benzene-hydrogen atom of which participates directly in the interaction with the receptor aromatic π plane.

Lignosulfonate Rapidly Inactivates Human Immunodeficiency and Herpes Simplex Viruses.

Background: Very few studies of the antiviral potential of lignosulfonates have been published. With the aim of oral application, among various groups of natural products, the relative antiviral potency of lignosulfonate and its ability to rapidly inactivate viruses were investigated. Methods: As target cells, MT-4 cells in suspension and attached Vero cells were used for infections with human immunodeficiency virus (HIV) and human herpes simplex type-1 virus (HSV). Mock- or virus-infected cells were incubated for 3-5 days with various concentrations of test samples, and the viable cell number was determined with the MTT method. For the shorter exposure experiments, higher titers of HIV or HSV were exposed to test samples for 10 or 3 min, diluted to a normal multiplicity of infection (MOI), and applied to the cells. Antiviral activity was quantified by using the chemotherapy index. Results: In the long-exposure system, lignosulfonates showed comparable anti-HIV activity with those of AZT, ddC, and sulfated polysaccharides, and it exceeded those of hundreds of tannins and flavonoids. When the exposure time was shortened, the chemotherapeutic index of the lignosulfonates for HIV was increased 27-fold. At a physiological pH, lignosulfonate showed higher anti-HIV activity than commercial alkali-lignin, dealkali-lignin, and humic acid, possibly due to the higher solubility and purity. Conclusions: With their rapid virus-inactivation capabilities, lignosulfonates may be useful for the prevention or treatment of virally induced oral diseases.

Evaluation of a new point-of-care quantitative reverse transcription polymerase chain test for detecting severe acute respiratory syndrome coronavirus 2.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is rapidly spreading worldwide, and the resultant disease, coronavirus disease (COVID-19), has become a global pandemic. Although there are multiple methods for detecting SARS-CoV-2, there are some issues with such tests, including long processing time, expense, low sensitivity, complexity, risk of contamination, and user friendly. This study evaluated the reproducibility and usability of a new point-of-care test (POCT) using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) for detecting SARS-CoV-2. METHODS: Samples from 96 patients with suspected SARS-CoV-2 infection were assessed using the real-time qRT-PCR-based POCT and the conventional real-time qRT-PCR method based on the Japanese National Institute of Infectious Diseases guidelines (registration number: jRCT1032200025). RESULTS: The real-time qRT-PCR-based POCT had a positive agreement rate of 90.0% (18/20), a negative agreement rate of 100% (76/76), and a total agreement rate of 97.9% (94/96), and the significantly high score of questionnaire survey (total score p < 0.0001). In the two cases in which real-time qRT-PCR-based POCT results did not match conventional real-time qRT-PCR test results, the SARS-CoV-2 RNA copy numbers were 8.0 copies per test in one case and below the detection limit in the other case when quantified using conventional real-time qRT-PCR. All patients could be triaged within 1 day using the real-time qRT-PCR-based POCT without invalid reports. CONCLUSIONS: The real-time qRT-PCR-based POCT not only had high reproducibility and useability but also allowed rapid patient triage. Therefore, it may be helpful in clinical settings.

Re-Evaluation of Chemotherapeutic Potential of Pyoktanin Blue.

Background: Pyoktanin blue (PB) is used for staining tissues and cells, and it is applied in photodynamic therapy due to its potent bactericidal activity. However, clinical application of PB as an antiviral and antitumor agent has been limited due to its potent toxicity. For clinical application, the antitumor and antiviral activity as well as the neurotoxicity of PB were re-evaluated with a chemotherapeutic index. Methods: Tumor-specificity (TS) was determined by the ratio of CC50 against normal oral cells/oral squamous cell carcinoma (OSCC); neurotoxicity by that of normal oral/neuronal cells; antiviral activity by that of mock-infected/virus-infected cells; and potency-selectivity expression (PSE) by dividing TS by CC50 (OSCC). Results: Antitumor activity of PB (assessed by TS and PSE) was comparable with that of DXR and much higher than that of 5-FU and melphalan. PB induced caspase-3 activation and subG1 cell accumulation in an OSCC cell line (Ca9-22). PB and anticancer drugs showed comparable cytotoxicity against both neuronal cells and OSCC cell lines. PB showed no detectable anti-HIV/HSV activity, in contrast to reverse transferase inhibitors, sulfated glucans, and alkaline extract of leaves of S.P. Conclusions: PB showed first-class anticancer activity and neurotoxicity, suggesting the importance of establishing the safe treatment schedule.

Quantification of the Ability of Natural Products to Prevent Herpes Virus Infection.

Background: Herpes simplex virus (HSV) is usually dormant and becomes apparent when body conditions decline. We investigated the anti-HSV activity of various natural and synthetic compounds for future clinical application. Methods: Mock- and HSV-infected Vero cells were treated for three days with various concentrations of samples. For short exposure, 100-fold concentrated virus were preincubated for 3 min with samples, diluted to normal multiplicity of infection (MOI), before the addition to the cells. Anti-HSV activity was evaluated by the chemotherapy index. Results: Alkaline extracts of the leaves of Sasa sp. (SE) and pine cone (PCE) showed higher anti-HSV activity than 20 Japanese traditional herb medicines (Kampo formulas), four popular polyphenols, and 119 chromone-related compounds. Exposure of HSV to SE or PCE for 3 min almost completely eliminated the infectivity of HSV, whereas much longer exposure time was required for Kakkonto, the most active Kampo formulae. Anti-HSV activity of PCE and Kakkonto could be detected only when they were dissolved by alkaline solution (pH 8.0), but not by neutral buffer (pH 7.4). Anti-HSV activity of SE and povidone iodine was stable if they were diluted with neutral buffer. Conclusions: The present study suggests the applicability of SE and PCE for treatment of oral HSV and possibly other viruses.

Elucidation of anti-HIV mechanism of sulfated cellobiose-polylysine dendrimers.

Three new spherical sulfated cellobiose-polylysine dendrimers of increasing generations bearing negatively charged sulfate groups were prepared by sulfating the corresponding cellobiose-polylysine dendrimers. The first, second, and third-generation derivatives exhibited potent anti-HIV activity with EC50 values of 3.7, 0.6, and 1.5 µg/mL, respectively, in constant to sulfated oligosaccharides with low anti-HIV activity, while the second-generation sulfated dendrimer was the most active. Surface plasmon resonance measurements with poly-l-lysine bearing positively charged amino acids as a model of the HIV surface glycoprotein gp120, indicated that the second-generation dendrimer had the lowest dissociation constant (KD = 1.86 × 10-12 M). Both the particle size and ζ potential increased in the presence of poly-l-lysine. It was proven that the moderate distance between the terminal sulfated cellobiose units in the second-generation dendrimer favored the high anti-HIV activity, owing to the electrostatic interactions developed due to the cluster effect.

Role of a long-chain alkyl group in sulfated alkyl oligosaccharides with high anti-HIV activity revealed by SPR and DLS.

Although a long-chain alkyl group in sulfated oligosaccharides can enhance the anti-HIV activity, the exact mechanism is unclear. To elucidate the role of the long-chain alkyl group, its interaction with a liposome (100 nm) as a HIV model was investigated by surface plasmon resonance and dynamic light scattering. The newly synthesized sulfated 1-(decadecyl-1, 2, 3-triazole)-1-deoxy- maltoheptaoside bearing the long-chain alkyl group was found to interact with the liposome. The particle size increased and the ζ potential was negative, indicating that the sulfated alkyl maltoheptaoside was attached to the liposome by the long-chain alkyl group and the fixed sulfated maltoheptaoside moiety was covered on the liposome. Thus, the long-chain alkyl group penetrates and is fixed into the lipid bilayer of HIV and the sulfated maltoheptaose moiety with negatively charged sulfate groups was electrostatically interacted with HIV gp120 molecule with positively charged amino acids to achieve the inhibition of HIV infection.