We use stochastic rotation dynamics (SRD) to examine the dynamics of the ejection of an initially strongly confined flexible polymer from a spherical capsid with and without hydrodynamics. The results obtained using stochastic rotation dynamics (SRD) are compared to similar Langevin simulations. Inclusion of hydrodynamic modes speeds up the ejection but also allows the part of the polymer outside the capsid to expand closer to equilibrium. This shows as higher values of radius of gyration when hydrodynamics are enabled. By examining the waiting times of individual polymer beads, we find that the waiting time t_{w} grows with the number of ejected monomers s as a sum of two exponents. When ≈63% of the polymer has ejected, the ejection enters the regime of slower dynamics. The functional form of t_{w} versus s is universal for all ejection processes starting from the same initial monomer densities. Inclusion of hydrodynamics only reduces its magnitude. Consequently, we define a universal scaling function h such that the cumulative waiting time t=N_{0}h(s/N_{0}) for large N_{0}. Our unprecedentedly precise measurements of force indicate that this form for t_{w}(s) originates from the corresponding force toward the pore decreasing superexponentially at the end of the ejection. Our measured t_{w}(s) explains the apparent superlinear scaling of the ejection time with the polymer length for short polymers. However, for asymptotically long polymers, t_{w}(s) predicts linear scaling.
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http://dx.doi.org/10.1103/PhysRevE.95.052418 | DOI Listing |
Heliyon
November 2024
Institute for the Protection of Cultural Heritage of Slovenia, Poljanska 40, 1000, Ljubljana, Slovenia.
This study investigates the effect of hydraulic shock waves on inactivation of MS-2 bacteriophage, a norovirus surrogate. A falling circular jet of water spiked with the MS-2 (∼1000 PFU/mL) was repeatedly impacted by a rotating blade, resulting in occurrence of hydraulic shock waves within the liquid region adjacent to the impact. The proof-of-concept rotational generator of hydraulic shock treating 9 L of water spiked with viruses was able to achieve 3 logs reduction of viral plaque count within 80-100 liquid passes at moderate blade impact velocities (namely, 70 and 88 m/s) despite the water temperature not exceeding 40 °C and no detectible cavitation.
View Article and Find Full Text PDFAntiviral Res
November 2024
Arbutus Biopharma Inc., Warminster, PA, USA.
HBV capsid assembly modulators (CAMs) target the core protein and inhibit pregenomic RNA encapsidation and viral replication. HBV CAMs also interfere with cccDNA formation during de novo infection, which in turn suppresses transcription and production of HBV antigens. In this report, we describe the antiviral activities of AB-836, a potent and highly selective HBV CAM.
View Article and Find Full Text PDFACS Med Chem Lett
September 2024
Arbutus Biopharma, Inc., 701 Veterans Circle, Warminster, Pennsylvania 18974, United States.
Isoquinolinone-based HBV capsid assembly modulators that bind at the dimer:dimer interface of HBV core protein have been shown to suppress viral replication in chronic hepatitis B patients. Analysis of their binding mode by protein X-ray crystallography has identified a region of the small molecule where the application of a constraint can lock the preferred binding conformation and has allowed for further optimization of this class of compounds. Key analogues demonstrated single digit nM EC values in reducing HBV DNA in a HepDE19 cellular assay in addition to favorable ADME and pharmacokinetic properties, leading to a high degree of oral efficacy in a relevant hydrodynamic injection mouse model of HBV infection, with effecting a 3 log decline in serum HBV DNA levels at a once daily dose of 1 mg/kg.
View Article and Find Full Text PDFEur J Med Chem
May 2024
Key Laboratory of Tropical Biological Resources of Ministry of Education and One Health Institute, School of Pharmaceutical Sciences, Hainan University, Haikou, 570228, China. Electronic address:
Hepatitis B virus (HBV) capsid assembly modulators (CAMs) represent a promising therapeutic approach for the treatment of HBV infection. In this study, the hit compound CDI (IC = 2.46 ± 0.
View Article and Find Full Text PDFNanotechnology
February 2024
Department of Biological Science and Technology, National Yang Ming Chiao Tung University, 30068 Hsinchu, Taiwan.
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