The evolution of new SARS‐CoV‐2 variants around the globe has made the COVID‐19 pandemic more worrisome, further pressuring the health care system and immunity. Novel variations that are unique to the receptor‐binding motif (RBM) of the receptor‐binding domain (RBD) spike glycoprotein, i. e. L452R‐E484Q, may play a different role in the B.1.617 (also known as G/452R.V3) variant's pathogenicity and better survival compared to the wild type. Therefore, a thorough analysis is needed to understand the impact of these mutations on binding with host receptor (RBD) and to guide new therapeutics development. In this study, we used structural and biomolecular simulation techniques to explore the impact of specific mutations (L452R‐E484Q) in the B.1.617 variant on the binding of RBD to the host receptor ACE2. Our analysis revealed that the B.1.617 variant possesses different dynamic behaviours by altering dynamic‐stability, residual flexibility and structural compactness. Moreover, the new variant had altered the bonding network and structural‐dynamics properties significantly. MM/GBSA technique was used, which further established the binding differences between the wild type and B.1.617 variant. In conclusion, this study provides a strong impetus to develop novel drugs against the new SARS‐CoV‐2 variants.
This paper proposes a hybrid hyperthermia treatment system, utilizing two noninvasive modalities for treating brain tumors. The proposed system depends on focusing electromagnetic (EM) and ultrasound (US) energies. The EM hyperthermia subsystem enhances energy localization by incorporating a multichannel wideband setting and coherent-phased-array technique. A genetic algorithm based optimization tool is developed to enhance the specific absorption rate (SAR) distribution by reducing hotspots and maximizing energy deposition at tumor regions. The treatment performance is also enhanced by augmenting an ultrasonic subsystem to allow focused energy deposition into deep tumors. The therapeutic faculty of ultrasonic energy is assessed by examining the control of mechanical alignment of transducer array elements. A time reversal (TR) approach is then investigated to address challenges in energy focus in both subsystems. Simulation results of the synergetic effect of both modalities assuming a simplified model of human head phantom demonstrate the feasibility of the proposed hybrid technique as a noninvasive tool for thermal treatment of brain tumors.
The evolution of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants around the globe has made the coronavirus disease 2019 (COVID-19) pandemic more worrisome, pressuring the health care system and resulting in an increased mortality rate. Recent studies recognized neuropilin-1 (NRP1) as a key facilitator in the invasion of the new SARS-CoV-2 into the host cell. Therefore, it is considered an imperative drug target for the treatment of COVID-19. Hence, a thorough analysis was needed to understand the impact and to guide new therapeutics development. In this study, we used structural and biomolecular simulation techniques to identify novel marine natural products which could block this receptor and stop the virus entry. We discovered that the binding affinity of CMNPD10175, CMNPD10017, CMNPD10114, CMNPD10115, CMNPD10020. CMNPD10018, CMNPD10153, CMNPD10149 CMNPD10464 and CMNPD10019 were substantial during the virtual screening (VS). We further explored these compounds by analyzing their absorption, distribution, metabolism, and excretion and toxicity (ADMET) properties and structural-dynamics features. Free energy calculations further established that all the compounds exhibit strong binding energy for NRP1. Consequently, we hypothesized that these compounds might be the best lead candidates for therapeutic interventions hindering virus binding to the host cell. This study provides a strong impetus to develop novel drugs against the SARS-CoV-2 by targeting NRP1.
This article presents efficient energy localization approach for hybrid wideband system for hyperthermia treatment of cancer based on a transmission line (TL). A heterogeneous head phantom is built by incorporating frequency dependent tissue properties of head layers considering both electromagnetic and ultrasound treatment. Effective medium properties are derived and used to compensate signal phase and magnitude values based on TL model. The obtained field map results emphasize the feasibility of the developed approach to obtain system parameters that enhance energy localization and eradicate hotspots.
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