| 1. |
- Haid, Sibylle, et al.
(författare)
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Repurposing screen identifies novel candidates for broad-spectrum coronavirus antivirals and druggable host targets
- 2024
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Ingår i: Antimicrobial Agents and Chemotherapy. - : American Society for Microbiology. - 0066-4804 .- 1098-6596. ; 68:3
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Tidskriftsartikel (refereegranskat)abstract
- Libraries composed of licensed drugs represent a vast repertoire of molecules modulating physiological processes in humans, providing unique opportunities for the discovery of host-targeting antivirals. We screened the Repurposing, Focused Rescue, and Accelerated Medchem (ReFRAME) repurposing library with approximately 12,000 molecules for broad-spectrum coronavirus antivirals and discovered 134 compounds inhibiting an alphacoronavirus and mapping to 58 molecular target categories. Dominant targets included the 5-hydroxytryptamine receptor, the dopamine receptor, and cyclin-dependent kinases. Gene knock-out of the drugs’ host targets including cathepsin B and L (CTSB/L; VBY-825), the aryl hydrocarbon receptor (AHR; Phortress), the farnesyl-diphosphate farnesyltransferase 1 (FDFT1; P-3622), and the kelch-like ECH-associated protein 1 (KEAP1; Omaveloxolone), significantly modulated HCoV-229E infection, providing evidence that these compounds inhibited the virus through acting on their respective host targets. Counter-screening of all 134 primary compound candidates with SARS-CoV-2 and validation in primary cells identified Phortress, an AHR activating ligand, P-3622-targeting FDFT1, and Omaveloxolone, which activates the NFE2-like bZIP transcription factor 2 (NFE2L2) by liberating it from its endogenous inhibitor KEAP1, as antiviral candidates for both an Alpha- and a Betacoronavirus. This study provides an overview of HCoV-229E repurposing candidates and reveals novel potentially druggable viral host dependency factors hijacked by diverse coronaviruses.
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| 2. |
- Hoa Nguyen, Tien, et al.
(författare)
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Performance Analysis and Optimization of the Coverage Probability in Dual Hop LoRa Networks With Different Fading Channels
- 2020
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Ingår i: IEEE Access. - : IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. - 2169-3536. ; 8, s. 107087-107102
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Tidskriftsartikel (refereegranskat)abstract
- In this work, the performance evaluation and the optimization of dual-hop LoRa network are investigated. In particular, the coverage probability (Pcov) of edge end-devices (EDs) is computed in closed-form expressions under various fading channels, i.e., Nakagami-m and Rayleigh fading. The Pcov under Nakagami-m fading is computed in the approximated closed-form expressions; the Pcov under Rayleigh fading, on the other hand, is calculated in the exact closed-form expressions. In addition, we also investigate the impact of different kinds of interference on the performance of the Pcov, i.e., intra-SF interference, inter-SF interference (or capture effect) and both intra- and inter-SF interference. Our findings show that the impact of imperfect orthogonality is not non-negligible, along with the intra-SF interference. Moreover, based on the proposed mathematical framework, we formulate an optimization problem, which finds the optimal location of the relay to maximize the coverage probability. Since it is a mixed integer program with a non-convex objective function, we decompose the original problem with discrete optimization variables into sub-problems with a convex feasible set. After that, each sub-problem is effectively solved by utilizing the gradient descent approach. Monte Carlo simulations are supplied to verify the correctness of our mathematical framework. In addition, the results manifest that our proposed optimization algorithm converges rapidly, and the coverage probability is significantly improved when the location of relay is optimized.
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| 3. |
- Lam, Thanh Tu, et al.
(författare)
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Performance Evaluation of Incremental Relaying in Underlay Cognitive Radio Networks with Imperfect CSI
- 2021
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Ingår i: IEEE ICCE 2020: 2020 IEEE EIGHTH INTERNATIONAL CONFERENCE ON COMMUNICATIONS AND ELECTRONICS (ICCE). - : IEEE. - 9781728154718 ; , s. 472-477
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Konferensbidrag (refereegranskat)abstract
- The performance of both primary and secondary networks in underlay cognitive radio networks (CRNs) with the help of incremental amplify and forward (IAF) relaying under imperfect channel state information (CSI) are investigated. Particularly, the interference probability at primary networks denoted by IP as well as the outage probability at secondary networks denoted by OP, are computed in the closed-form expressions. Our findings show that the impact of the imperfect CSI on the performance of IP is non-negligible. To tackle the high value of IP, reducing the transmit power at the secondary transmitters is a proper solution, it, however, will also increase the OP at the secondary networks. Thus, a simple power control coefficient is proposed to compromise the performance between two networks. Finally, Monte-Carlo simulations are provided to verify the accuracy of the proposed mathematical frameworks.
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