Repurposing existing drugs for monkeypox: applications of virtual screening methods

Li Vladimir,Lee Youngho,Lee Chul,Kim Heebal 한국유전학회 2023 Genes & Genomics Vol.45 No.11

Background Monkeypox is endemic to African region and has become of Global concern recently due to its outbreaks in non-endemic countries. Although, the disease was first recorded in 1970, no monkeypox specific drug or vaccine exists as of now. Methods We applied drug repositioning method, testing effectiveness of currently approved drugs against emerging disease, as one of the most affordable approaches for discovering novel treatment measures. Techniques such as virtual ligand-based and structure-based screening were applied to identify potential drug candidates against monkeypox. Results We narrowed down our results to 6 antiviral and 20 anti-tumor drugs that exhibit theoretically higher potency than tecovirimat, the currently approved drug for monkeypox disease. Conclusions Our results indicated that selected drug compounds displayed strong binding affinity for p37 receptor of monkeypox virus and therefore can potentially be used in future studies to confirm their effectiveness against the disease.

Prospects and Source Materials for Studies of the Korean Ethnic Minority in the Soviet Union

VLADIMIR F. LI The Academy of Korean Studies 1990 Korea Journal Vol.30 No.11

Korean Studies in the Soviet Union

VLADIMIR F. LI The Academy of Korean Studies 1990 Korea Journal Vol.30 No.1

Molecular dynamics simulation of pyruvate kinase to investigate improved thermostability of artificially selected strain in Enterococcus faecium

Li Vladimir,Lee Chul,Lee Youngho,Kim Heebal 한국유전학회 2023 Genes & Genomics Vol.45 No.6

Background Enterococcus faecium (E. faecium) is a member of symbiotic lactic acid bacteria in gastrointestinal tract and it was successfully used to treat diarrhea cases in humans. For a lactobacteria to survive during the pasteurization process, resistance of proteins to denaturation at high temperatures is crucial. Pyruvate kinase (PYK) is one of the proteins possessing such property. It plays a major role during glycolysis by producing pyruvate and adenosine triphosphate (ATP). Objective To assess the acquired thermostability of PYK of ALE strain using in silico methods. Methods First, we predicted and assessed tertiary structures of our proteins using SWISS-MODEL homology modelling server. Second, we then applied molecular dynamics (MD) simulation to simulate and assess multiple properties of molecules. Therefore, we implemented comparative MD to evaluate thermostability of PYK of recently developed high temperature resistant strain of E. faecium using Adaptive Laboratory Evolution (ALE) method. After 20ns of simulation at different temperatures, we observed that ALE enhanced strain demonstrated slightly better stability at 300, 340 and 350 K compared to that of the wild type (WT) strain. Results We collected the results of MD simulation at four temperature points: 300, 340, 350 and 400 K. Our results showed that the protein demonstrated increased stability at 340 and 350 K. Conclusion Results of these study suggest that PYK of ALE enhanced strain of E. faecium demonstrates overall better stability at elevated temperatures compared to that of WT strain.

In silico SARS-CoV-2 vaccine development for Omicron strain using reverse vaccinology

Li Vladimir,Lee Chul,Yoo DongAhn,Cho Seoae,Kim Heebal 한국유전학회 2022 Genes & Genomics Vol.44 No.8

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic began in 2019 but it remains as a serious threat today. To reduce and prevent spread of the virus, multiple vaccines have been developed. Despite the efforts in developing vaccines, Omicron strain of the virus has recently been designated as a variant of concern (VOC) by the World Health Organization (WHO). Objective: To develop a vaccine candidate against Omicron strain (B.1.1.529, BA.1) of the SARS-CoV-19. Methods: We applied reverse vaccinology methods for BA.1 and BA.2 as the vaccine target and a control, respectively. First, we predicted MHC I, MHC II and B cell epitopes based on their viral genome sequences. Second, after estimation of antigenicity, allergenicity and toxicity, a vaccine construct was assembled and tested for physicochemical properties and solubility. Third, AlphaFold2, RaptorX and RoseTTAfold servers were used to predict secondary structures and 3D structures of the vaccine construct. Fourth, molecular docking analysis was performed to test binding of our construct with angiotensin converting enzyme 2 (ACE2). Lastly, we compared mutation profiles on the epitopes between BA.1, BA.2, and wild type to estimate the efficacy of the vaccine. Results: We collected a total of 10 MHC I, 9 MHC II and 5 B cell epitopes for the final vaccine construct for Omicron strain. All epitopes were predicted to be antigenic, non-allergenic and non-toxic. The construct was estimated to have proper stability and solubility. The best modelled tertiary structures were selected for molecular docking analysis with ACE2 receptor. Conclusions: These results suggest the potential efficacy of our newly developed vaccine construct as a novel vaccine candidate against Omicron strain of the coronavirus.

Genetic individualization of sable (Martes zibellina L. 1758) using microsatellites

Bo Li,DanWu,Yingying Cai,Monakhov Vladimir G,Wei Zhang,Yanchun Xu 한국통합생물학회 2018 Animal cells and systems Vol.22 No.4

Genetic individualization based on non-invasive sampling is crucial for estimating the numbers of individuals in endangered mammalian populations. In sable (Martes zibellina)-poaching cases, identifying the number of animals involved is critical for determining the penalty. In addition, investigating animal numbers for wild sable populations requires genetic individualization when collecting several samples in neighboring regions. Microsatellites have been demonstrated to be reliable markers for individual identification. Thirty-three microsatellite loci derived from Mustelidae were selected to develop a genetic individualization method for sable. Three reference populations containing 54 unrelated sables were used to calculate allele number, allelic frequencies, and the polymorphic information content of each locus. The data were subsequently used to assess the validity of a combination of twelve loci for sable individualization. We defined twelve polymorphic loci that were easy to be amplified and genotyped. Four significant deviations from Hardy-Weinberg equilibrium were observed among the 12 loci in the three populations. The match probability of an individual from the reference populations with a random individual based on the 12 loci was 1.37 × 10−13. Using the combination of the twelve loci provides sufficient power to individualize sables considering the levels of microsatellite polymorphism observed. These loci were successfully applied to a case of sable poaching and provided valid evidence to determine the penalty. The genetic individualization of sable based on these loci might also be useful to investigate the numbers of animals in wild populations.

Improving Sub-seasonal Precipitation and Temperature Outlooks with Deep Learning

Yun Fan,Vladimir Krasnoplsky,Li Xu,Jon Gottschalck 한국기상학회 2022 한국기상학회 학술대회 논문집 Vol.2022 No.10

Changes in Cell Membrane Fatty Acid Composition of Streptococcus thermophilus in Response to Gradually Increasing Heat Temperature

민봉규,김꽃님,Vladimir Li,조서애,김희발 한국미생물·생명공학회 2020 Journal of microbiology and biotechnology Vol.30 No.5

In this study, a method of heat adaptation was implemented in an attempt to increase the upper thermal threshold of two Streptococcus thermophilus found in South Korea and identified the alterations in membrane fatty acid composition to adaptive response to heat. In order to develop heat tolerant lactic acid bacteria, heat treatment was continuously applied to bacteria by increasing temperature from 60°C until the point that no surviving cell was detected. Our results indicated significant increase in heat tolerance of heat-adapted strains compared to the wild type (WT) strains. In particular, the survival ratio of basically low heat-tolerant strain increased even more. In addition, the strains with improved heat tolerance acquired cross protection, which improved their survival ratio in acid, bile salts and osmotic conditions. A relation between heat tolerance and membrane fatty acid composition was identified. As a result of heat adaptation, the ratio of unsaturated to saturated fatty acids (UFA/SFA) and C18:1 relative concentration were decreased. C6:0 in only heatadapted strains and C22:0 in only the naturally high heat tolerant strain were detected. These results support the hypothesis, that the consequent increase of SFA ratio is a cellular response to environmental stresses such as high temperatures, and it is able to protect the cells from acid, bile salts and osmotic conditions via cross protection. This study demonstrated that the increase in heat tolerance can be utilized as a mean to improve bacterial tolerance against various environmental stresses.

Six unrecorded macrofungi from the Royal Tombs (Donggureung and Seooreung) of the Joseon Dynasty and Jongmyo Shrine, Korea

조해진,임영운,Vladimir Li,Suldbold Jargalmaa,김남규,김민지,이현 국립생물자원관 2018 Journal of species research Vol.7 No.1

Macrofungi are visible to the naked eye and play important ecological roles in nutrient cycles as decomposers and symbionts in forest ecosystems. Collectively, macrofungi have great potential as valuable resources for food, cosmetics, and medicinal uses. We surveyed the Royal Tombs (Donggureung and Seooreung) of the Joseon Dynasty and Jongmyo Shrine, where the surrounding vegetation is well-preserved, to investigate indigenous macrofungi. During surveys in 2015-2016, we discovered six macrofungi that were previously not recorded to Korea. They were identified to the species level using morphological features and phylogenetic analysis based on the internal transcribed spacer region: Cruentomycena kedrovaya, Dacrymyces aureosporus, Laetiporus versisporus, Parasola setulosa, Piptoporellus soloniensis, and Pluteus longistriatus. The detailed morphological descriptions and molecular analysis are provided in this study.

Experimental studies of damage to aircraft skin under the influence of raindrops

Minggong Sha,Ying Sun,Li Yulong,Vladimir I. Goncharenko,Vladimir S. Oleshko,Anatoly V. Ryapukhin,Victor M. Yurov Techno-Press 2023 Advances in aircraft and spacecraft science Vol.10 No.6

Airplanes in flight collide with raindrops, and the leading edges of the airframe can be damaged when colliding with raindrops. A single waterjet testing platform was created to study rain erosion damage. Carbon fiber samples with three types of skins were studied and the mechanical properties were measured using a nanoindentation instrument. The research results show that the impact force on the sample increases with the continuous increase in the impact speed of raindrops, which leads to an increase in the damage area. Sheathing with low surface roughness is more damaged than other sheathings due to its rougher surface, and the result proves that surface roughness has a more significant effect on rain erosion damage to sheathings compared to their hardness.