Infection of dengue virus (DENV) was number of globally significant emerging pathogen. Antiviral dengue therapies are importantly needed to control emerging dengue. Dengue virus (DENV) is mosquito-borne arboviruses responsible for causing acute systemic diseases and grievous health conditions in humans. To date, there is no clinically approved dengue vaccine or antiviral for humans, even though there have been great efforts towards this end. Copper and copper compounds have more effective in inactivation viruses, likes an influenza virus and human immunodeficiency virus (HIV). Purpose in this project was investigated of
Infeksi virus dengue (DENV) adalah patogen yang muncul secara global. Terapi antivirus dengue penting diperlukan untuk mengontrol muncul dengue. Dengue virus (DENV) disebabkan oleh mosquito-borne arboviruses yang menyebabkan penyakit sistemik akut dan kondisi kesehatan pada manusia. Sampai saat ini, tidak ada vaksin dengue klinis disetujui atau antivirus bagi manusia, meskipun telah ada upaya besar menjelang akhir ini. Tembaga dan senyawa tembaga memiliki efektivitas dalam inaktivasi virus, seperti virus influenza dan human immunodeficiency virus (HIV). Tujuan dalam proyek ini adalah menyelidiki senyawa antiviral
Background: Dengue is a kind of infectious disease that was distributed in the tropical and subtropical areas. To date, there is no clinically approved dengue vaccine or antiviral for humans, even though there have been great efforts towards this end. Therefore, finding the effective compound against dengue virus (DENV) replication is very important. Among the complex compounds, copper(II)-imidazole derivatives are of interest because of their biological and medicinal benefits. Materials and Methods: In the present study, antiviral activity of [Cu(2,4,5-triphenylimidazole) 2 ] n , was evaluated against different stages of dengue virus type 2 (DENV-2) replication in Vero cell using focus forming unit reduction assay and quantitative ELISA. Results: [Cu(2,4,5-triphenylimidazole) 2 ] n inhibited DENV-2 replication in Vero cells with IC 50 = 2.3 μg/ml and SI= 19.42 when cells were treated 2 days after virus infection, whereas its CC 50 for cytotoxicity to Vero cells was 44.174 μg/ml. Conclusion: The compound has high anti-DENV2 activity, less toxicity, and a high possibility to be considered a drug candidate.
Dengue virus (DENV), from the genus flavivirus of the family flaviviridae, causes serious health problems globally. Human monoclonal antibodies (HuMAb) can be used to elucidate the mechanisms of neutralization and antibody-dependent enhancement (ADE) of DENV infections, leading to the development of a vaccine or therapeutic antibodies. Here, we generated eight HuMAb clones from an Indonesian patient infected with DENV. These HuMAbs exhibited the typical characteristics of weak neutralizing antibodies including high cross-reactivity with other flaviviruses and targeting of the fusion loop epitope (FLE). However, one of the HuMAbs, 3G9, exhibited strong neutralization (NT50 < 0.1 μg/ml) and possessed a high somatic hyper-mutation rate of the variable region, indicating affinity-maturation. Administration of this antibody significantly prolonged the survival of interferon-α/β/γ receptor knockout C57BL/6 mice after a lethal DENV challenge. Additionally, Fc-modified 3G9 that had lost their in vitro ADE activity showed enhanced therapeutic potency in vivo and competed strongly with an ADE-prone antibody in vitro. Taken together, the affinity-matured FLE-targeting antibody 3G9 exhibits promising features for therapeutic application including a low NT50 value, potential for treatment of various kinds of mosquito-borne flavivirus infection, and suppression of ADE. This study demonstrates the therapeutic potency of affinity-matured FLE-targeting antibodies.
Coronavirus disease (COVID-19), which was due to novel coronavirus was detected in December 2019 in Wuhan, China for the first time and spread rapidly became a global pandemic. This study aimed to predict the potential of macroalgae compounds as SARS-CoV-2 antiviral by inhibiting of ACE2 receptor through in silico approach. Twenty-seven macroalgae compounds were obtained from PubChem (NCBI, USA), while target protein ACE2 receptor was collected from Protein Data Bank (PDB). Then the initial screening study drug-likeness conducted by Lipinski rule of five web server and prediction of bioactive probability carried out by PASS (Prediction of activity spectra for biologically active substances) Online web server. After those compounds were approved by Lipinski’s rule of five and PASS online prediction web server, the blind docking simulation was performed using PyRx 0.8 software to show binding energy value. Molecular interaction analysis was done using BIOVIA Discovery Studio 2016 v16.1.0 and PyMOL v2.4.1 software. There are six macroalgae compounds approved by Lipinski’s rule of five and PASS Online Analysis. The result is that macroalgae compound siphonaxanthin among 27 macroalgae compound showed strong binding energy to bind ACE2 receptor with -8.8 kcal/mol. This study also used the SARS-CoV-2 drugs as positive control: remdesivir, molnupiravir, baricitinib, lopinavir, oseltamivir, and favipiravir. The result shows that siphonaxanthin has lowest binding energy than the common SARS-CoV-2 drug. Macroalgae compounds are predicted to have potential as SARS-CoV-2 antiviral. Thus, extension studies need to investigate by in vitro and in vivo analysis for confirmation the siphonaxanthin’s inhibitory activity in combat SARS-CoV-2.
During the coronavirus disease 2019 (COVID-19) pandemic, some countries, including Indonesia, have faced a double burden with regards to disease control. As Indonesia is a tropical country, it serves as a suitable host for disease vectors and multiple microorganisms of causative agents of disease. In total, five of the neglected tropical diseases (NTDs) should be a consideration in Indonesia during the COVID-19 pandemic, including leprosy, yaws, filariasis, soil-transmitted helminths and schistosomiasis. The present review summarises the preparedness of Indonesia in facing NTDs during the COVID-19 pandemic. Strengthening government leadership will be a valuable factor for combating NTDs in Indonesia. For instance, strong leadership can lead to precise management, by increasing the number of health facilities, engaging in active case identification, conducting health campaigns and instituting new regulations to prevent the stigmatization faced by patients. Preventive medicine in the first level of health facilities can be prioritized and presented to the community via health campaigns, health advocacy and improvement in follow-up after active case surveillance. Government-supported integrated management is also a key component in eliminating NTD. Moreover, healthy lifestyle campaigns that include social distancing, wearing a mask and regularly washing hands should be promoted continuously to reduce the transmission of COVID-19, which is potentially associated with a poor outcome in individuals with NTDs. This review concluded that the Indonesian government should strengthen their efforts toward NTD control using alternative methods, such as involving key citizens in the collaboration of the detection of new cases and introducing mobile health as a means of detecting health problems or following up on patient progress. To reduce the transmission of COVID-19, testing, tracing and treatment must be improved, so that the gap between suspected cases and confirmed cases of COVID-19 can be closed. If the transmission of COVID-19 can be decreased, case detection and efforts toward NTD control can be conducted effectively.
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