Lassa hemorrhagic fever,caused by Lassa mammarenavirus(LASV)infection,accumulates up to 5000 deaths every year.Currently,there is no vaccine available to combat this disease.In this study,a library of 200 bioactive co...Lassa hemorrhagic fever,caused by Lassa mammarenavirus(LASV)infection,accumulates up to 5000 deaths every year.Currently,there is no vaccine available to combat this disease.In this study,a library of 200 bioactive compounds was virtually screened to study their drug-likeness with the capacity to block theα-dystroglycan(α-DG)receptor and prevent LASV influx.Following rigorous absorption,distribution,metabolism,and excretion(ADME)and quantitative structure-activity relationship(QSAR)profiling,molecular docking was conducted with the top ligands against theα-DG receptor.The compounds chrysin,reticuline,and 3-caffeoylshikimic acid emerged as the top three ligands in terms of binding affinity.Post-docking analysis revealed that interactions with Arg76,Asn224,Ser259,and Lys302 amino acid residues of the receptor protein were important for the optimum binding affinity of ligands.Molecular dynamics simulation was performed comprehensively to study the stability of the protein-ligand complexes.In-depth assessment of root-mean-square deviation(RMSD),root mean square fluctuation(RMSF),polar surface area(PSA),B-Factor,radius of gyration(Rg),solvent accessible surface area(SASA),and molecular surface area(MolSA)values of the protein-ligand complexes affirmed that the candidates with the best binding affinity formed the most stable protein-ligand complexes.To authenticate the potentialities of the ligands as target-specific drugs,an in vivo study is underway in real time as the continuation of the research.展开更多
The authors consider a robust optimal reinsurance and investment problem in a risk model with two dependent classes of insurance business for an Ambiguity-Averse insurer(AAI).The insurer aims to minimize the goal-reac...The authors consider a robust optimal reinsurance and investment problem in a risk model with two dependent classes of insurance business for an Ambiguity-Averse insurer(AAI).The insurer aims to minimize the goal-reaching probability that the value of the wealth process reaches a low barrier before a high goal.Using the stochastic control approach based on the Hamilton-JacobiBellman(HJB)equation,the authors derive the robust optimal reinsurance and investment strategies,as well as the corresponding value function.The authors conclude that the robust optimal investmentreinsurance strategy coincides with the one without model ambiguity,but the value function differs.As a consequence,ignoring model uncertainty leads to significant value function loss for the AAI.Besides,it is worth noting that if the insurer has only one business,the sum of the degenerated value function and the one of(Luo,et al.,2019)is equal to 1 both for ambiguity and ambiguity-neutral.Finally,numerical examples are given to illustrate our results.展开更多
文摘Lassa hemorrhagic fever,caused by Lassa mammarenavirus(LASV)infection,accumulates up to 5000 deaths every year.Currently,there is no vaccine available to combat this disease.In this study,a library of 200 bioactive compounds was virtually screened to study their drug-likeness with the capacity to block theα-dystroglycan(α-DG)receptor and prevent LASV influx.Following rigorous absorption,distribution,metabolism,and excretion(ADME)and quantitative structure-activity relationship(QSAR)profiling,molecular docking was conducted with the top ligands against theα-DG receptor.The compounds chrysin,reticuline,and 3-caffeoylshikimic acid emerged as the top three ligands in terms of binding affinity.Post-docking analysis revealed that interactions with Arg76,Asn224,Ser259,and Lys302 amino acid residues of the receptor protein were important for the optimum binding affinity of ligands.Molecular dynamics simulation was performed comprehensively to study the stability of the protein-ligand complexes.In-depth assessment of root-mean-square deviation(RMSD),root mean square fluctuation(RMSF),polar surface area(PSA),B-Factor,radius of gyration(Rg),solvent accessible surface area(SASA),and molecular surface area(MolSA)values of the protein-ligand complexes affirmed that the candidates with the best binding affinity formed the most stable protein-ligand complexes.To authenticate the potentialities of the ligands as target-specific drugs,an in vivo study is underway in real time as the continuation of the research.
基金supported by the Natural Science Foundation of Hunan Province under Grant No.2023JJ30381the Changsha Municipal Natural Science Foundation under Grant No.kq2208159+2 种基金the Humanities and Social Science Fund of Ministry of Education of China under Grant No.23YJC910008the Graduate Research and Innovation Project of Hunan Province under Grant No.CX20230241the Graduate Research and Innovation Project of Central South University under Grant No.1053320222639。
文摘The authors consider a robust optimal reinsurance and investment problem in a risk model with two dependent classes of insurance business for an Ambiguity-Averse insurer(AAI).The insurer aims to minimize the goal-reaching probability that the value of the wealth process reaches a low barrier before a high goal.Using the stochastic control approach based on the Hamilton-JacobiBellman(HJB)equation,the authors derive the robust optimal reinsurance and investment strategies,as well as the corresponding value function.The authors conclude that the robust optimal investmentreinsurance strategy coincides with the one without model ambiguity,but the value function differs.As a consequence,ignoring model uncertainty leads to significant value function loss for the AAI.Besides,it is worth noting that if the insurer has only one business,the sum of the degenerated value function and the one of(Luo,et al.,2019)is equal to 1 both for ambiguity and ambiguity-neutral.Finally,numerical examples are given to illustrate our results.
