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INTRODUCTION: Indonesia has made progress in increasing vaccine coverage, but equitable access remains challenging, especially in remote areas. Despite including vaccines in the National Immunization Program (NIP), coverage has not met WHO and UNICEF targets, with childhood immunization decreasing during the COVID-19 pandemic. COVID-19 vaccination has also experienced hesitancy, slowing efforts to end the pandemic. SCOPE: This article addresses the issue of vaccine hesitancy and its impact on vaccination initiatives amidst the COVID-19 pandemic. This article utilizes the vaccine hesitancy framework to analyze previous outbreaks of vaccine-preventable diseases and their underlying causes, ultimately providing recommendations for addressing the current situation. The analysis considers the differences between the pre-pandemic circumstances and the present and considers the implementation of basic and advanced strategies. KEY FINDINGS AND CONCLUSION: Vaccine hesitancy is a significant challenge in the COVID-19 pandemic, and public health campaigns and community engagement efforts are needed to promote vaccine acceptance and uptake. Efforts to address vaccine hesitancy promote trust in healthcare systems and increase the likelihood of individuals seeking preventive health services. Vaccine hesitancy requires a comprehensive, culturally sensitive approach that considers local contexts and realities. Strategies should be tailored to specific cultural and societal contexts and monitored and evaluated.

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Marennine, a blue pigment produced by the blue diatom Haslea ostrearia, is known to have some biological activities. This pigment is responsible for the greening of oysters on the West Coast of France. Other new species of blue diatom, H. karadagensis, H. silbo sp. inedit., H. provincialis sp. inedit, and H. nusantara, also produce marennine-like pigments with similar biological activities. Aside from being a potential source of natural blue pigments, H. ostrearia-like diatoms present a commercial potential for the aquaculture, food, cosmetics, and health industries. Unfortunately, for a hundred years, the exact molecular structure of this bioactive compound has remained a mystery. A lot of hypotheses regarding the chemical structure of marennine have been proposed. The recent discovery of this structure revealed that it is a macromolecule, mainly carbohydrates, with a complex composition. In this study, some glycoside hydrolases were used to digest marennine, and the products were further analyzed using nuclear magnetic resonance (NMR) and mass spectroscopy (MS). The reducing sugar assay showed that marennine was hydrolyzed only by endo-1,3-ß-glucanase. Further insight into the structure of marennine was provided by the spectrum of 1H NMR, MS, a colorimetric assay, and a computational study, which suggest that the chemical structure of marennine contains 1,3-ß-glucan.

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The global pandemic of COVID-19 caused by SARS-CoV-2 has caused more than 400 million infections with more than 5.7 million deaths worldwide, and the number of validated therapies from natural products for treating coronavirus infections needs to be increased. Therefore, the virtual screening of bioactive compounds from natural products based on computational methods could be an interesting strategy. Among many sources of bioactive natural products, compounds from marine organisms, particularly microalgae and cyanobacteria, can be potential antiviral agents. The present study investigates bioactive antiviral compounds from microalgae and cyanobacteria as a potential inhibitor of SARS-CoV-2 by targeting Angiotensin-Converting Enzyme II (ACE2) using integrated in silico and in vitro approaches. Our in silico analysis demonstrates that C-Phycocyanin (CPC) can potentially inhibit the binding of ACE2 receptor and SARS-CoV-2 with the docking score of -9.7 kcal mol-1. This score is relatively more favorable than the native ligand on ACE2 receptor. Molecular dynamics simulation also reveals the stability interaction between both CPC and ACE2 receptor with a root mean square deviation (RMSD) value of 1.5 Å. Additionally, our in vitro analysis using the surface plasmon resonance (SPR) method shows that CPC has a high affinity for ACE2 with a binding affinity range from 5 to 125 µM, with KD 3.37 nM. This study could serve as a reference to design microalgae- or cyanobacteria-based antiviral drugs for prophylaxis in SARS-CoV-2 infections.

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Vaccination, despite being recognized as one of the most effective primary public health measures, is viewed as unsafe and unnecessary by an increasing number of individuals. Anxiety about vaccines and vaccination programs leading to vaccine hesitancy results from a complex mix of social and political influences, cultural and religious beliefs, the availability of and ability to interpret health and scientific information, and personal and population experiences of health systems and government policies. Vaccine hesitancy is becoming a serious threat to vaccination programs, and was identified as one of the World Health Organization's top ten global health threats in 2019. The negative impact of anti-vaccination movements is frequently cited as one of the major reasons for rising vaccine hesitancy amongst the general public world-wide. This review discusses the various issues surrounding vaccine hesitancy and the anti-vaccine movement, starting with the definitions of vaccine hesitancy and the anti-vaccine movement in their early history and in the modern era, before discussing the key drivers of vaccine hesitancy, particularly across different regions of the world, with a focus on various countries with low-, middle-, or high-income economies with different socio-economic populations. The review concludes with the impact of vaccine hesitancy on herd immunity and social, psychological, and public health measures to counter vaccine hesitancy.

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Neuraminidase (NA) is an enzyme that prevents virions from aggregating within the host cell and promotes cell-to-cell spread by cleaving glycosidic linkages to sialic acid. The best-known neuraminidase is the viral neuraminidase, which present in the influenza virus. Thus, the development of anti-influenza drugs that inhibit NA has emerged as an important and intriguing approach in the treatment of influenza. Garcinia atroviridis L. (GA) dried fruits (GAF) are used commercially as seasoning and in beverages. The main objective of this study was to identify a new potential neuraminidase inhibitor from GA. A bioassay-guided fractionation method was applied to obtain the bioactive compounds leading to the identification of garcinia acid and naringenin. In an enzyme inhibition study, garcinia acid demonstrated the highest activity when compared to naringenin. Garcinia acid had the highest activity, with an IC50 of 17.34-17.53 µg/mL or 91.22-92.21 µM against Clostridium perfringens-NA, and 56.71-57.85 µg/mL or 298.32-304.31 µM against H1N1-NA. Based on molecular docking results, garcinia acid interacted with the triad arginine residues (Arg118, Arg292, and Arg371) of the viral neuraminidase, implying that this compound has the potential to act as a NA enzyme inhibitor.

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Influenza remains one of the major public health concerns because it causes annual epidemics and can potentially instigate a global pandemic. Numerous countermeasures, including vaccines and antiviral treatments, are in use against seasonal influenza infection; however, their effectiveness has always been discussed due to the ongoing resistance to antivirals and relatively low and unpredictable efficiency of influenza vaccines compared to other vaccines. The growing interest in vaccines as a promising approach to prevent and control influenza may provide alternative vaccine development options with potentially increased efficiency. In addition to currently available inactivated, live-attenuated, and recombinant influenza vaccines on the market, novel platforms such as virus-like particles (VLPs) and nanoparticles, and new vaccine formulations are presently being explored. These platforms provide the opportunity to design influenza vaccines with improved properties to maximize quality, efficacy, and safety. The influenza vaccine manufacturing process is also moving forward with advancements relating to egg- and cell-based production, purification processes, and studies into the physicochemical attributes and vaccine degradation pathways. These will contribute to the design of more stable, optimized vaccine formulations guided by contemporary analytical testing methods and via the implementation of the latest advances in the field.

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<b>Background and Objective:</b> Inflammation occurs <i>via</i> several mechanisms, one of which includes the production of Nitric Oxide (NO) catalyzed by inducible nitric oxide synthase (iNOS), which is inhibited selectively by isothioureas. <i>Ageratum conyzoides</i> L. has shown activity in reducing pain and inflammation, although the molecular mechanism had not been undertaken. The objectives of this work were (1) to study the mechanism of anti-inflammatory activity of <i>A. conyzoides</i> through inhibition of iNOS, (2) to correlate the iNOS inhibitory activity of the plant with the total flavonoid content of the plants and (3) to identify the flavonol synthase (FLS), an enzyme that catalyzes the production of quercetin. <b>Materials and Methods:</b> The inhibitory activity against iNOS was assayed by <i>in vitro</i> method. The total flavonoids (calculated as quercetin) of <i>A. conyzoides</i> were determined by fluorometry. The protein extraction of the leaves was carried out by employing Laing and Christeller's (2004) method, followed with SDS-PAGE. <b>Results:</b> The inhibitory activity (IC₅₀) of ethanol extract and ethyl acetate fraction of <i>A. conyzoides</i> against iNOS was 92.05 and 4.78 µg mL¹, respectively. Pearson correlation analysis resulted in 0.548 (ethanol extract) and 0.696 (ethyl acetate fraction). The total flavonoids (calculated as quercetin) contained in the ethanol extract and ethyl acetate fraction of <i>A. conyzoides</i> were 0.71 and 7.65%, respectively. The FLS in <i>A. conyzoides</i> leaves was identified at 31 kDa. <b>Conclusion:</b> <i>A. </i>c<i>onyzoides</i> L. is potential in inhibiting iNOS due to quercetin contained in the leaves. This report will add a scientific insight of <i>A. conyzoides</i> for biological sciences.

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The COVID-19 pandemic has shaken the world since early 2020 and its health, social, economic, and societal negative impacts at the global scale have been catastrophic. Since the early days of the pandemic, development of safe and effective vaccines was judged to be the best possible tool to minimize the effects of this pandemic. Drastic public health measures were put into place to stop the spread of the virus, with the hope that vaccines would be available soon. Thanks to the extraordinary commitments of many organizations and individuals from around the globe and the collaborative effort of many international scientists, vaccines against COVID-19 received regulatory approval for emergency human use in many jurisdictions in less than a year after the identification of the viral sequence. Several of these vaccines have been in use for some time; however, the pandemic is still ongoing and likely to persist for the foreseeable future. This is due to many reasons including reduced compliance with public health restrictions, limited vaccine manufacturing/distribution capacity, high rates of vaccine hesitancy, and the emergence of new variants with the capacity to spread more easily and to evade current vaccines. Here we discuss the discovery and availability of COVID-19 vaccines and evolving issues around mass vaccination programs.

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Matrix metalloproteinase9 (MMP9) is known to be highly expressed during metastatic cancer where most known potential inhibitors failed in the clinical trials. This study aims to select local plants in our state, as anti-breast cancer agent with hemopexin-like domain of MMP9 (PEX9) as the selective protein target. In silico screening for PEX9 inhibitors was performed from our in house-natural compound database to identify the plants. The selected plants were extracted using methanol and then a step-by-step in vitro screening against MMP9 was performed from its crude extract, partitions until fractions using FRET-based assay. The partitions were obtained by performing liquid-liquid extraction on the methanol extract using n-hexane, ethylacetate, n-butanol, and water representing nonpolar to polar solvents. The fractions were made from the selected partition, which demonstrated the best inhibition percentage toward MMP9, using column chromatography. Of the 200 compounds screened, 20 compounds that scored the binding affinity -11.2 to -8.1 kcal/mol toward PEX9 were selected as top hits. The binding of these hits were thoroughly investigated and linked to the plants which they were reported to be isolated from. Six of the eight crude extracts demonstrated inhibition toward MMP9 with the IC50 24 to 823 µg/mL. The partitions (1 mg/mL) of Ageratum conyzoides aerial parts and Ixora coccinea leaves showed inhibition 94% and 96%, whereas their fractions showed IC50 43 and 116 µg/mL, respectively toward MMP9. Using MTT assay, the crude extract of Ageratum exhibited IC50 22 and 229 µg/mL against 4T1 and T47D cell proliferations, respectively with a high safety index concluding its potential anti-breast cancer from herbal.

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Previous studies have reported that compounds bearing an arylamide linked to a heterocyclic planar ring have successfully inhibited the hemopexin-like domain (PEX9) of matrix metalloproteinase 9 (MMP9). PEX9 has been suggested to be more selectively targeted than MMP9's catalytic domain in a degrading extracellular matrix under some pathologic conditions, especially in cancer. In this study, we aim to synthesize and evaluate 10 arylamide compounds as MMP9 inhibitors through an enzymatic assay as well as a cellular assay. The mechanism of inhibition for the most active compounds was investigated via molecular dynamics simulation (MD). Molecular docking was performed using AutoDock4.0 with PEX9 as the protein model to predict the binding of the designed compounds. The synthesis was carried out by reacting aniline derivatives with 3-bromopropanoyl chloride using pyridine as the catalyst at room temperature. The MMP9 assay was conducted using the FRET-based MMP9 kits protocol and gelatin zymography assay. The cytotoxicity assay was done using the MTT method, and the MD simulation was performed using AMBER16. Assay on MMP9 demonstrated activities of three compounds (2, 7, and 9) with more than 50% inhibition. Further inhibition on MMP9 expressed by 4T1 showed that two compounds (7 and 9) inhibited its gelatinolytic activity more than 50%. The cytotoxicity assay against 4T1 cells results in the inhibition of the cell growth with an EC50 of 125 µM and 132 µM for 7 and 9, respectively. The MD simulation explained a stable interaction of 7 and 9 in PEX9 at 100 ns with a free energy of binding of -8.03 kcal/mol and -6.41 kcal/mol, respectively. Arylamides have potential effects as selective MMP9 inhibitors in inhibiting breast cancer cell progression.

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Traditional herbal medicine in Indonesia is still in great demand and popular in society. The Indonesian government regulations state that herbal medicine should not contain chemical drug due to the toxic effect of uncontrolled consumption. Allopurinol is one of the drugs commonly added to herbal medicine for the treatment of chronic gout. Paper-based analytical device is one of the latest forms of analysis that has been widely used for the identification of chemical elements, environmental contamination, bacteria, and many more. In this study, experiments were conducted using Whatman filter paper No. 1, No. 2, and No. 4 and Whatman chromatography as a paper, and 9 colorimetric reagents were tested for allopurinol detection in herbal medicine. There were 5 specific reagents that reacted positively with allopurinol and only 3 reagents that can be applied to the paper, that is, Folin-Ciocalteu, Tollens, and p-DAB reagent. The results of the optimization show that the most optimal immersion time was 60 minutes with a drying time of 30 minutes at 50°C. Each filter paper has different characteristic; however, there was no significant difference when all of the papers were used as PAD for allopurinol detection.