Vaccine hesitancy and equity: lessons learned from the past and how they affect the COVID-19 countermeasure in Indonesia.

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.

The nanomolar affinity of C-phycocyanin from virtual screening of microalgal bioactive as potential ACE2 inhibitor for COVID-19 therapy.

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.

Arylamide as Potential Selective Inhibitor for Matrix Metalloproteinase 9 (MMP9): Design, Synthesis, Biological Evaluation, and Molecular Modeling.

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.