Cluster-based text mining for extracting drug candidates for the prevention of COVID-19 from the biomedical literature.

Objective: The coronavirus disease 2019 (COVID-19) health crisis that began at the end of 2019 made researchers around the world quickly race to find effective solutions. Related literature exploded and it was inevitable that an automated approach was needed to find useful information, namely text mining, to overcome COVID-19, especially in terms of drug candidate discovery. While text mining methods for finding drug candidates mostly try to extract bioentity associations from PubMed, very few of them mine with a clustering approach. The purpose of this study was to demonstrate the effectiveness of our approach to identify drugs for the prevention of COVID-19 through literature review, cluster analysis, drug docking calculations, and clinical trial data. Methods: This research was conducted in four main stages. First, the text mining stage was carried out by involving Bidirectional Encoder Representations from Transformers for Biomedical to obtain vector representation of each word in the sentence from texts. The next stage generated the disease-drug associations, which were obtained from the correlation between disease and drug. Next, the clustering stage grouped the rules through the similarity of diseases by utilizing Term Frequency-Inverse Document Frequency as its feature. Finally, the drug candidate extraction stage was processed through leveraging PubChem and DrugBank databases. We further used the drug docking package AUTODOCK VINA in PyRx software to verify the results. Results: Comparative analyses showed that the percentage of findings using mining with clustering outperformed mining without clustering in all experimental settings. In addition, we suggest that the top three drugs/phytochemicals by drug docking analysis may be effective in preventing COVID-19. Conclusions: The proposed method for text mining utilizing the clustering method is quite promising in the discovery of drug candidates for the prevention of COVID-19 through the biomedical literature.

Do Kombucha Symbiotic Cultures of Bacteria and Yeast Affect Bacterial Cellulose Yield in Molasses?

Bacterial cellulose (BC) is a valuable biopolymer typically observed in Kombucha with many potential food applications. Many studies highlight yeast's roles in providing reducing sugars, used by the bacteria to grow and produce BC. However, whether yeast could enhance the BC yields remains unclear. This study investigates the effect of yeast Dekkera bruxellensis on bacteria Komagataeibacter intermedius growth and BC production in molasses medium. The results showed that the co-culture stimulated K. intermedius by ~2 log CFU/mL, which could be attributed to enhanced reducing sugar utilization. However, BC yields decreased by ~24%, suggesting a negative impact of D. bruxellensis on BC production. In contrast to other studies, regardless of D. bruxellensis, K. intermedius increased the pH to ~9.0, favoring the BC production. Furthermore, pH increase was slower in co-culture as compared to single culture cultivation, which could be the reason for lower BC yields. This study indicates that co-culture could promote synergistic growth but results in the BC yield reduction. This knowledge can help design a more controlled fermentation process for optimum bacterial growth and, ultimately, BC production.

Genetic Admixture in the Culturally Unique Peranakan Chinese Population in Southeast Asia.

The Peranakan Chinese are culturally unique descendants of immigrants from China who settled in the Malay Archipelago ∼300-500 years ago. Today, among large communities in Southeast Asia, the Peranakans have preserved Chinese traditions with strong influence from the local indigenous Malays. Yet, whether or to what extent genetic admixture co-occurred with the cultural mixture has been a topic of ongoing debate. We performed whole-genome sequencing (WGS) on 177 Singapore (SG) Peranakans and analyzed the data jointly with WGS data of Asian and European populations. We estimated that Peranakan Chinese inherited ∼5.62% (95% confidence interval [CI]: 4.76-6.49%) Malay ancestry, much higher than that in SG Chinese (1.08%, 0.65-1.51%), southern Chinese (0.86%, 0.50-1.23%), and northern Chinese (0.25%, 0.18-0.32%). A sex-biased admixture history, in which the Malay ancestry was contributed primarily by females, was supported by X chromosomal variants, and mitochondrial (MT) and Y haplogroups. Finally, we identified an ancient admixture event shared by Peranakan Chinese and SG Chinese ∼1,612 (95% CI: 1,345-1,923) years ago, coinciding with the settlement history of Han Chinese in southern China, apart from the recent admixture event with Malays unique to Peranakan Chinese ∼190 (159-213) years ago. These findings greatly advance our understanding of the dispersal history of Chinese and their interaction with indigenous populations in Southeast Asia.

Immunogenicity and structural efficacy of P41 of Plasmodium sp. as potential cross-species blood-stage malaria vaccine.

Vaccine based strategies offer a promising future in malaria control by generating protective immunity against natural infection. However, vaccine development is hindered by the Plasmodium sp. genetic diversity. Previously, we have shown P41 protein from 6-Cysteine shared by Plasmodium sp. and could be used for cross-species anti-malaria vaccines. Two different approaches, ancestral, and consensus sequence, could produce a single target for all human-infecting Plasmodium. In this study, we investigated the efficacy of ancestral and consensus of P41 protein. Phylogenetic and time tree reconstruction was conducted by RAXML and BEAST2 package to determine the relationship of known P41 sequences. Ancestral and consensus sequences were reconstructed by the GRASP server and Unipro Ugene software, respectively. The structural prediction was made using the Psipred and Rosetta program. The protein characteristic was analyzed by assessing hydrophobicity and Post-Translational Modification sites. Meanwhile, the immunogenicity score for B-cell, T-cell, and MHC was determined using an immunoinformatic approach. The result suggests that ancestral and consensus have a distinct protein characteristic with high immunogenicity scores for all immune cells. We found one shared conserved epitope with phosphorylation modification from the ancestral sequence to target the cross-species vaccine. Thus, this study provides detailed insight into P41 efficacy for the cross-species anti-malaria blood-stage vaccine.

Structural and immunogenicity analysis of reconstructed ancestral and consensus P48/45 for cross-species anti malaria transmission-blocking vaccine.

The development of the anti-malaria vaccine holds a promising future in malaria control. One of the anti-malaria vaccine strategies known as the transmission-blocking vaccine (TBV) is to inhibit the parasite transmission between humans and mosquitoes by targeting the parasite gametocyte. Previously, we found that P48/45 included in the 6-Cysteine protein family shared by Plasmodium sp. We also detected vaccine properties possessed by all human-infecting Plasmodium and could be used as a cross-species anti-malaria vaccine. In this study, we investigated the efficacy of P48/45 through the ancestral and consensus reconstruction approach. P48/45 phylogenetic and time tree analysis was done by RAXML and BEAST2. GRASP server and Ugene software were used to reconstruct ancestral and consensus sequences, respectively. The protein structural prediction was made by using a psipred and Rosetta program. Each protein characteristic of P48/45 was analyzed by assessing hydrophobicity and Post-Translational Modification sites. Meanwhile, the Epitope sequence for B-cell, T-cell, and HLA was determined using an immunoinformatics approach. Lastly, molecular docking simulation was done to determine native binding interactions of P48/45-P230. The result showed a distinct protein characteristic of ancestral and consensus sequences. The immunogenicity analysis revealed the number of epitopes in the ancestral sequence is greater than the consensus sequence. The study also found a conserved epitope located in the binding site and consists of specific Post-Translational Modification sites. Hence, our research provides detailed insight into ancestral and consensus P48/45 efficacy for the cross-species anti-malaria vaccine.

In silico investigation of potential inhibitors to main protease and spike protein of SARS-CoV-2 in propolis.

Docking analysis of propolis's natural compound was successfully performed against SARS-CoV-2 main protease (Mpro) and spike protein subunit 2 (S2). Initially, the propolis's protein was screened using chromatography analysis and successfully identified 22 compounds in the propolis. Four compounds were further investigated, i.e., neoblavaisoflavone, methylophiopogonone A, 3'-Methoxydaidzin, and genistin. The binding affinity of 3'-Methoxydaidzin was -7.7 kcal/mol, which is similar to nelfinavir (control), while the others were -7.6 kcal/mol. However, we found the key residue of Glu A:166 in the methylophiopogonone A and genistin, even though the predicted binding energy slightly higher than nelfinavir. In contrast, the predicted binding affinity of neoblavaisoflavone, methylophiopogonone A, 3'-Methoxydaidzin, and genistin against S2 were -8.1, -8.2, -8.3, and -8.3 kcal/mol, respectively, which is far below of the control (pravastatin, -7.3 kcal/mol). Instead of conventional hydrogen bonding, the π bonding influenced the binding affinity against S2. The results reveal that this is the first report about methylophiopogonone A, 3'-Methoxydaidzin, and genistin as candidates for anti-viral agents. Those compounds can then be further explored and used as a parent backbone molecule to develop a new supplementation for preventing SARS-CoV-2 infections during COVID-19 outbreaks.