Prediction of the interaction between Calloselasma rhodostoma venom-derived peptides and cancer-associated hub proteins: A computational study.

The use of peptide drugs to treat cancer is gaining popularity because of their efficacy, fewer side effects, and several advantages over other properties. Identifying the peptides that interact with cancer proteins is crucial in drug discovery. Several approaches related to predicting peptide-protein interactions have been conducted. However, problems arise due to the high costs of resources and time and the smaller number of studies. This study predicts peptide-protein interactions using Random Forest, XGBoost, and SAE-DNN. Feature extraction is also performed on proteins and peptides using intrinsic disorder, amino acid sequences, physicochemical properties, position-specific assessment matrices, amino acid composition, and dipeptide composition. Results show that all algorithms perform equally well in predicting interactions between peptides derived from venoms and target proteins associated with cancer. However, XGBoost produces the best results with accuracy, precision, and area under the receiver operating characteristic curve of 0.859, 0.663, and 0.697, respectively. The enrichment analysis revealed that peptides from the Calloselasma rhodostoma venom targeted several proteins (ESR1, GOPC, and BRD4) related to cancer.

Bibliometric Analysis of Literature in Snake Venom-Related Research Worldwide (1933-2022).

Snake envenomation is a severe economic and health concern affecting countries worldwide. Snake venom carries a wide variety of small peptides and proteins with various immunological and pharmacological properties. A few key research areas related to snake venom, including its applications in treating cancer and eradicating antibiotic-resistant bacteria, have been gaining significant attention in recent years. The goal of the current study was to analyze the global profile of literature in snake venom research. This study presents a bibliometric review of snake venom-related research documents indexed in the Scopus database between 1933 and 2022. The overall number of documents published on a global scale was 2999, with an average annual production of 34 documents. Brazil produced the highest number of documents (n = 729), followed by the United States (n = 548), Australia (n = 240), and Costa Rica (n = 235). Since 1963, the number of publications has been steadily increasing globally. At a worldwide level, antivenom, proteomics, and transcriptomics are growing hot issues for research in this field. The current research provides a unique overview of snake venom research at global level from 1933 through 2022, and it may be beneficial in guiding future research.

Anti-Breast Cancer Activity on MCF-7 Cells of Melittin from Indonesia's Apis cerana: An In Vitro Study.

OBJECTIVE: Breast cancer is the most common case of cancers. Apitheraphy has been traditionally used for abundance diseases. This study aims to evaluate and compare the anti-breast cancer activity of melittin from Indonesia's Apic cerana as a potential drug for treating breast cancer. METHODS: Apis cerana bee venom (BV) was collected from a bee farm in Cikurutung, Bandung using an electrical venom device. The BV was then purified using the ÄKTA Start system and HiTrap™ SP HP cation exchange chromatography column. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was used to identify melittin based on its molecular mass and lowry's protein assay to measure melittin concentration. Melittin cytotoxicity was measured with brine shrimp lethality test (BSLT), while MCF-7 breast cancer cells MTT assay was used to measure its anti-breast cancer activity, based on inhinition rate. RESULTS: 95.432 µg/mL melittin is purified from 62.8 mg/L BV, using  cation exchange chromatography. Melittin in vitro analysis with MCF-7 MTT assay is used to determine anti-breast cancer activity in dose dependent manner. Furthermore, melttin BSLT result showed a LC50 16.67675 µg/mL. Therefore, the MTT assay  was conducted in 5, 10 and 15 µg/mL with MCF-7 inhibition values of 0.768 ± 0.014, 3.303 ± 0.011, and 35.714 ± 0.009 %, respectively. CONCLUSION: Indonesia's Apis cerana has the potential to be used as a therapeutic peptide for breast cancer treatment.

Potential hepatoprotective effects of flavonoids contained in propolis from South Sulawesi against chemotherapy agents.

The use of doxorubicin and epirubicin as chemotherapy agent causes side effects such as liver damage due to oxidative stress by reactive oxygen species (ROS) that cause increased of ALT and AST level as liver parameter. One source of natural antioxidants as ROS neutralizer comes from flavonoid that contain in propolis. Most researchers claim that flavonoid can be used to protect the liver. The aim of this study was to test the hepatoprotective effect of flavonoid in propolis from South Sulawesi against doxorubicin and epirubicin. The experiment included male Sprague dawley rats divided into nine groups. The rats received the microcapsule propolis or the quercetin orally for 15 days. The hepatotoxicity was promoted by injection epirubicin and doxorubicin (i.v.) with a cumulative dose of 9 mg/kg. In this study, total polyphenol and flavonoid tests of propolis have been carried out, there were 1.1% polyphenols and 2.7% flavonoids, the antioxidant activity tests showed IC50 value of 9849 ppm and LCMS/MS tests supported the presence of phenolic compounds in propolis from South Sulawesi. Liver parameter was measured and the results showed that the propolis 200 mg/kg group produced the lowest ALT and had potential protective effect against doxorubicin and epirubicin-induced hepatotoxicity.

Evaluating the potency of Sulawesi propolis compounds as ACE-2 inhibitors through molecular docking for COVID-19 drug discovery preliminary study.

Coronavirus disease (COVID-19) is a global pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Up to date, there has been no specific cure to treat the disease. Indonesia is one of the countries that is still fighting to control virus transmission. Yet, at the same time, Indonesia has a rich biodiversity of natural medicinal products that potentially become an alternative cure. Thus, this study examined the potency of a natural medicinal product, Sulawesi propolis compounds produced by Tetragonula sapiens, inhibiting angiotensin-converting activity enzyme-2 (ACE-2), a receptor of SARS-CoV-2 in the human body. In this study, molecular docking was done to analyze the docking scores as the representation of binding affinity and the interaction profiles of propolis compounds toward ACE-2. The results illustrated that by considering the docking score and the presence of interaction with targeted sites, five compounds, namely glyasperin A, broussoflavonol F, sulabiroins A, (2S)-5,7-dihydroxy-4'-methoxy-8-prenylflavanone and isorhamnetin are potential to inhibit the binding of ACE-2 and SARS-CoV-2, with the docking score of -10.8, -9.9, -9.5, -9.3 and -9.2 kcal/mol respectively. The docking scores are considered to be more favorable compared to MLN-4760 as a potent inhibitor.

Molecular interaction analysis of Sulawesi propolis compounds with SARS-CoV-2 main protease as preliminary study for COVID-19 drug discovery.

Coronavirus disease 2019 (COVID-19), a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global health concern, as the World Health Organization declared this outbreak to be a global pandemic in March 2020. The need for an effective treatment is urgent because the development of an effective vaccine may take years given the complexity of the virus and its rapid mutation. One promising treatment target for COVID-19 is SARS-CoV-2 main protease. Thus, this study was aimed to examine whether Sulawesi propolis compounds produced by Tetragonula sapiens inhibit the enzymatic activity of SARS-CoV-2 main protease. In this study, molecular docking was performed to analyze the interaction profiles of propolis compounds with SARS-CoV-2 main protease. The results illustrated that two compounds, namely glyasperin A and broussoflavonol F, are potential drug candidates for COVID-19 based on their binding affinity of -7.8 kcal/mol and their ability to interact with His41 and Cys145 as catalytic sites. Both compounds also displayed favorable interaction profiles with SARS-CoV-2 main protease with binding similarities compared to inhibitor 13b as positive control 63% and 75% respectively.

Surface plasmon resonance analysis for detecting non-structural protein 1 of dengue virus in Indonesia.

Dengue is an acute febrile disease caused by dengue virus (DENV) that is transmitted by Aedes sp., which causes serious health conditions in many countries. Non-structural protein 1 (NS1) is a co-factor for the RNA replication of this virus, which represents a new strategy for the identification of dengue. Prompt and accurate laboratory diagnosis of this infection is required to assist in patient triage and management, as well as prevent the spread of this infection. In the present study, we tested the potential of surface plasmon resonance (SPR) as a diagnostic tool for dengue infections. NS1 antigen protein was used as an analyte that targets anti-NS1 antibodies, with their interaction resulting in a change in the refractive index. In comparison to currently available gold-standard detection methods [enzyme-linked immunosorbent assay (ELISA) and reverse transcription polymerase chain reaction (RT-PCR)], SPR showed a similar sensitivity but greater efficiency and simplicity in terms of infection detection. Out of 26 samples collected from patients with dengue in Indonesia, SPR was able to correctly identify all 16 positively infected individuals at a lower concentration and a shorter period of time compared to ELISA and RT-PCR. This study revealed that SPR is a promising tool for DENV detection and potentially other diseases as well.

Antiviral activity of Acanthaster planci phospholipase A2 against human immunodeficiency virus.

AIM: Investigation of antiviral activity of Acanthaster planci phospholipase A2 (AP-PLA2) from moluccas to human immunodeficiency virus (HIV). MATERIALS AND METHODS: Crude venom (CV) and F20 (PLA2 with 20% fractioned by ammonium sulfate) as a sample of PLA 2 obtained from A. planci's extract were used. Enzymatic activity of PLA2 was determined using the degradation of phosphatidylcholine (PC). Activity test was performed using in vitro method using coculture of phytohemagglutinin-stimulated peripheral blood mononuclear cell (PBMC) from a blood donor and PBMC from HIV patient. Toxicity test of AP-PLA2 was done using lethal concentration required to kill 50% of the population (LC50). RESULTS: AP-PLA2 F20 had activity and purity by 15.66 times bigger than CV. The test showed that the LC50 of AP-PLA2 is 1.638 mg/ml. Antiviral analysis of AP-PLA2 in vitro showed the inhibition of HIV infection to PBMC. HIV culture with AP-PLA2 and without AP-PLA2 has shown the number of infected PBMC (0.299±0.212% and 9.718±0.802%). Subsequently, RNA amplification of HIV using reverse transcriptase-polymerase chain reaction resulted in the decrease of band intensity in gag gene of HIV. CONCLUSION: This research suggests that AP-PLA2 has the potential to develop as an antiviral agent because in vitro experiment showed its ability to decrease HIV infection in PBMC and the number of HIV ribonucleic acid in culture.

Size-reduced embryos reveal a gradient scaling-based mechanism for zebrafish somite formation.

Little is known about how the sizes of animal tissues are controlled. A prominent example is somite size, which varies widely both within an individual and across species. Despite intense study of the segmentation clock governing the timing of somite generation, how it relates to somite size is poorly understood. Here, we examine somite scaling and find that somite size at specification scales with the length of the presomitic mesoderm (PSM) despite considerable variation in PSM length across developmental stages and in surgically size-reduced embryos. Measurement of clock period, axis elongation speed and clock gene expression patterns demonstrate that existing models fail to explain scaling. We posit a 'clock and scaled gradient' model, in which somite boundaries are set by a dynamically scaling signaling gradient across the PSM. Our model not only explains existing data, but also makes a unique prediction that we confirm experimentally - the formation of periodic 'echoes' in somite size following perturbation of the size of one somite. Our findings demonstrate that gradient scaling plays a central role in both progression and size control of somitogenesis.