Background: To overcome the several drawbacks of warfarin, non-vitamin K antagonist oral anticoagulants (NOACs) were developed. Even though randomized controlled trials (RCTs) provided high-quality evidence, the real-world evidence is still needed. This systematic review and meta-analysis proposed to measure the safety and efficacy profile between warfarin and NOACs in non-valvular atrial fibrillation (NVAF) patients in preventing stroke.Results: We collected articles about the real-world studies comparing warfarin and NOACs for NVAF patients recorded in electronic scientific databases such as Embase, ProQuest, PubMed, and Cochrane. The pooled hazard ratio (HR) and 95% confidence interval (CI) were estimated using the generic inverse variance method. A total of 34 real-world studies, including 2287288 NVAF patients, were involved in this study. NOACs effectively reduced the stroke risk than warfarin (HR 0.77; 95% CI 0.69 to 0.87;p< 0.01). Moreover, NOACs effectively lowered all-cause mortality risk (HR 0.71; 95% CI 0.63 to 0.81;p< 0.01). From the safety aspect, compared to warfarin, NOACs significantly reduced major bleeding risk (HR 0.68; 95% CI 0.54 to 0.86;p< 0.01) and intracranial bleeding risk (HR 0.54; 95% CI 0.42 to 0.70;p< 0.01). However, NOACs administration failed to decrease gastrointestinal bleeding risk (HR 0.78; 95% CI 0.58 to 1.06;p= 0.12).Conclusions: In NVAF patients, NOACs were found to be more effective than warfarin at reducing stroke risk. NOACSs also lowered the risk of all-cause mortality, cerebral hemorrhage, and severe bleeding in NVAF patients compared to warfarin.

Malaria is one of the life‐threatening diseases in the world. The spread of resistance to antimalarial drugs is a major challenge, and resistance to artemisinin has been reported in the Southeast Asian region. In the previous study, the active compound of Streptomyces hygroscopicus subsp. Hygroscopicus (S. hygroscopicus), eponemycin, has been shown to have antimalarial effects. To further analyze the effects of other active compounds on the Plasmodium parasite, identifying and analyzing the effectiveness of compounds contained in S. hygroscopicus through instrumentation of liquid chromatography/mass spectrometry (LC/MS) and in silico studies were very useful. This study aimed at identifying other derivative compounds from S. hygroscopicus and screening the antimalarial activity of the compound by assessing the binding affinity, pharmacokinetic profile, and bond interaction. The derivative compounds were identified using LC/MS. Protein targets for derivative compounds were found through literature studies, and the results of identification of compounds and protein targets were reconstructed into three‐dimensional models. Prediction of pharmacokinetic profiles was carried out using Swiss ADME. Screening of protein targets for the derivative compound was carried out using the reverse molecular docking method. Analyzing bond interaction was done by LigPlot. One compound from S. hygroscopicus, i.e., 6,7‐dinitro‐2‐[1, 2, 4]triazole‐4‐yl‐benzo[de]isoquinoline‐1,3‐dione, was successfully identified using LC/MS. This compound was an isoquinoline derivative compound. Through literature studies with inclusion criteria, thirteen protein targets were obtained for reverse molecular docking. This isoquinoline derivative had the potential to bind to each protein target. The pharmacokinetic profile showed that this compound had the drug‐likeness criteria. Conclusion. 6,7‐Dinitro‐2‐[1, 2, 4]triazole‐4‐yl‐benzo[de]isoquinoline‐1,3‐dione has antimalarial activity as shown by reverse molecular docking studies and pharmacokinetic profiles. The best inhibitory ability of compounds based on bond affinity is with adenylosuccinate synthetase.

Background: For many people, especially in developing countries, herbal medicine is the most traditional drug choice to treat all diseases including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 infection). Propolis is one of the popular herbal medicine which has various health benefits, particularly antiviral activity. In this molecular docking study, this investigation examined twenty-five kinds of propolis to bind SARS-CoV-2 protein with the main targets of ACE-2 and M-Pro receptors. Method: Propolis ligands were downloaded from PubChem, meanwhile ACE-2 and M-Pro receptors were downloaded from Protein Data Bank. Both ligands and targets were optimized by Pymol. The pharmacokinetic analysis was conducted using SwissADME. Molecular docking was done using PyRx 0.9 and its binding interaction was visualized by Discovery Studio. To predict the potential inhibition, this study compared the ligand-protein complex of propolis to ligands from the previous study. Result: Through the Lipinski rule, only five of twenty-five types of propolis were not qualified for the criterion. The ability to bind protein targets were various between ligands, the highest affinity to ACE-2 receptors were abietic acid, galangin, chrysin, kaempferol and acacetin, respectively. The binding affinity between ligand and M-Pro were seen weaker than ACE-2 receptor, while the strongest were kaempferol, abietic acid, acacetin, galangin and chrysin, respectively. Conclusion: Â Kaempferol is the most potent form of propolis to bind to ACE-2 and M-Pro receptors by assessing the binding affinity and the amount of amino acid residue formation when compared to control ligands. Keywords: ACE-2 receptor, COVID-19, Main protease, Molecular docking, Propolis, SARS-CoV-2

Background: Malaria remains a major public health concern around the world. Microscopic blood smear examination continues to be the gold standard for diagnosis; however, it requires high technical skills and expertise, limiting diagnostic accuracy in resource-poor settings. Artificial intelligence (AI) has emerged as a promising tool to support malaria detection. This systematic review provides an overview of the diagnostic performance of AI-based systems for malaria diagnosis in a clinical setting. Methods: This study followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and involved articles within the last 10 years that were collected from PubMed, ScienceDirect, Cochrane, EBSCO, and Wiley Online Library. Original articles that reported AI diagnostic accuracy with external validation were involved. The quality of each study was evaluated using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). Results: Ten studies with 6754 patients were analyzed. Pooled results of sensitivity [87.7% (95% CI: 78.2–93.4)] and specificity [91.4% (95% CI: 77.3–97.1)] revealed how much the AI agrees with each method when that method is used as a gold standard. Additionally, AI achieved a sensitivity of 87.7% and a specificity of 91.4% compared to microscopy examination and a sensitivity of 90.7% and a specificity of 88.3% compared to polymerase chain reaction (PCR). Conclusions: AI-based systems improve malaria diagnosis by providing high accuracy, automation, and lower costs. Showing performance comparable to reference methods such as microscopy and PCR, AI is a promising complementary tool for malaria control.

Indonesia's diversity of natural resources presents an intriguing opportunity for the exploration of potential herbal medicines. Numerous compounds, both purified and crude, have been reported to exhibit antiviral activity. The ACE-2 receptor may be a therapeutic target for SARS-CoV-2 infection. We used a search engine to search for herbal medicines with ACE-2 inhibitory activity to predict the potential inhibition of natural compounds (i.e., theaflavin, deoxypodophyllotoxin, gallocatechin, allicin, quercetin, annonamine, Curcumin, 6-gingerol, and cucurbitacin B) to SARS-CoV2 – ACE-2 complex. We performed molecular docking analysis using the ACE-2 protein target from Protein Data Bank. Protein stabilization was carried out to adjust to the body's physiology, carried out using Pymol by removing water atoms and adding hydrogen atoms. Ligands of active compounds from natural resources were selected and downloaded from the PubChem database, then optimized by Pymol software. The complexes of the tested ligand compounds and ACE-2 receptors, which have a bond strength smaller than the control were selected for analysis. Theaflavin, Deoxypodophyllotoxin, Gallocatechin, Curcumin, and Cucurbitacin B had a strong bond affinity than the control ligands. Based on our data, deoxypodophylotoxin and Curcumin had the same interaction amino acid residus compare to the control ligand. This study concludes that deoxypodophyllotoxin and Curcumin have the greatest potential to inhibit the formation of the SARS-Cov2-ACE-2 complex; additionally, these compounds exhibit favorable pharmacological and pharmacodynamic properties. It is suggested that additional research be conducted to determine the biological effects of deoxypodopyllotoxin and Curcumin on ACE-2 receptors.

Context: Malaria is still a serious global health problem due to the development of drug resistance. It is necessary to find new drugs with renewable mechanisms that are effective in killing parasites. Our previous research has analyzed more than one compound of polyether ionophore group in ethyl acetate Streptomyces hygroscopicus subsp. hygroscopicus extract. Polyether ionophore is known to have a similar mechanism of action to chloroquine which is potent in inhibiting Plasmodium falciparum glutathione S-transferase (PfGST). Aims: To evaluate the potential effect of polyether ionophore toward PfGST as a target protein through molecular docking. Methods: PfGST was obtained from Protein Data Bank. Test ligands (polyether ionophore) and control ligands (chloroquine) were obtained from PubChem. Pharmacokinetic analysis was done using SwissADME, molecular docking using PyRx 0.9, visualization using LigPlot and PyMOL, and molecular dynamics using YASARA for the best ligand activity. Results: Lenoremycin had the highest binding affinity to PfGST (-8.53 kcal/mol) among other polyether ionophores, and nigericin had the best residue bonding with hydrophobic and hydrogen with a binding affinity of-8.25 kcal/mol compared to chloroquine complex in molecular docking and molecular dynamic simulation. Conclusions: Polyether ionophore could serve as an antimalarial agent better than chloroquine, with nigericin as the best compound candidate in inhibiting PfGST compared to other polyether ionophores.