NPJ vaccines
Authors: Kim IJ, Lanthier PA, Clark MJ, De La Barrera RA, Tighe MP, Szaba FM, Travis KL, Low-Beer TC, Cookenham TS, Lanzer KG, Bernacki DT, Johnson LL, Schneck AA, Ross CN, Tardif SD, Layne-Colon D, Mdaki SD, Dick EJ, Chuba C, Gonzalez O, Brasky KM, Dutton J, Rutherford JN, Coffey LL, Singapuri A, Martin CSS, Chiu CY, Thomas SJ, Modjarrad K, Patterson JL, Blackman MA
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Authors: Ganatra S, Dani SS, Ahmad J, Kumar A, Shah J, Abraham GM, McQuillen DP, Wachter RM, Sax PE
Journal of the American Geriatrics Society
Authors: Federman AD, Brody A, Ritchie CS, Egorova N, Arora A, Lubetsky S, Goswami R, Peralta M, Reckrey JM, Boockvar K, Shah S, Ornstein KA, Leff B, DeCherrie L, Siu AL
Critical care (London, England)
Authors: Vaara ST, Bhatraju PK, Stanski NL, McMahon BA, Liu K, Joannidis M, Bagshaw SM
Clinical genitourinary cancer
Authors: Talukder R, Makrakis D, Lin GI, Diamantopoulos LN, Dawsey S, Gupta S, Carril-Ajuria L, Castellano D, de Kouchkovsky I, Jindal T, Koshkin VS, Park JJ, Alva A, Bilen MA, Stewart TF, McKay RR, Tripathi N, Agarwal N, Vather-Wu N, Zakharia Y, Morales-Barrera R, Devitt ME, Cortellini A, Fulgenzi CAM, Pinato DJ, Nelson A, Hoimes CJ, Gupta K, Gartrell BA, Sankin A, Tripathi A, Zakopoulou R, Bamias A, Murgic J, Fr?be A, Rodriguez-Vida A, Drakaki A, Liu S, Lu E, Kumar V, Lorenzo GD, Joshi M, Isaacsson-Velho P, Buznego LA, Duran I, Moses M, Barata P, Sonpavde G, Wright JL, Yu EY, Montgomery RB, Hsieh AC, Grivas P, Khaki AR
MMWR. Morbidity and mortality weekly report
Authors: Heinzerling A, Vergara XP, Gebreegziabher E, Beckman J, Wong J, Nguyen A, Khan S, Frederick M, Bui D, Chan E, Gibb K, Rodriguez A, Jain S, Cummings KJ
Journal of clinical gastroenterology
Authors: Wang M, Wadhwani SI, Cullaro G, Lai JC, Rubin JB
Current problems in cardiology
Authors: Fudim M, Shahid I, Emani S, Klein L, Dupuy-McCauley KL, Zieroth S, Mentz RJ
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Authors: Marquez C, Chen Y, Atukunda M, Chamie G, Balzer LB, Kironde J, Ssemmondo E, Mwangwa F, Kabami J, Owaraganise A, Kakande E, Abbott R, Ssekyanzi B, Koss C, Kamya MR, Charlebois ED, Havlir DV, Petersen ML
Volume 28 of Issue 9 | Nature medicine
Authors: Hagey RJ, Elazar M, Pham EA, Tian S, Ben-Avi L, Bernardin-Souibgui C, Yee MF, Moreira FR, Rabinovitch MV, Meganck RM, Fram B, Beck A, Gibson SA, Lam G, Devera J, Kladwang W, Nguyen K, Xiong A, Schaffert S, Avisar T, Liu P, Rustagi A, Fichtenbaum CJ, Pang PS, Khatri P, Tseng CT, Taubenberger JK, Blish CA, Hurst BL, Sheahan TP, Das R, Glenn JS
Influenza A virus's (IAV's) frequent genetic changes challenge vaccine strategies and engender resistance to current drugs. We sought to identify conserved and essential RNA secondary structures within IAV's genome that are predicted to have greater constraints on mutation in response to therapeutic targeting. We identified and genetically validated an RNA structure (packaging stem-loop 2 (PSL2)) that mediates in vitro packaging and in vivo disease and is conserved across all known IAV isolates. A PSL2-targeting locked nucleic acid (LNA), administered 3 d after, or 14 d before, a lethal IAV inoculum provided 100% survival in mice, led to the development of strong immunity to rechallenge with a tenfold lethal inoculum, evaded attempts to select for resistance and retained full potency against neuraminidase inhibitor-resistant virus. Use of an analogous approach to target SARS-CoV-2, prophylactic administration of LNAs specific for highly conserved RNA structures in the viral genome, protected hamsters from efficient transmission of the SARS-CoV-2 USA_WA1/2020 variant. These findings highlight the potential applicability of this approach to any virus of interest via a process we term 'programmable antivirals', with implications for antiviral prophylaxis and post-exposure therapy.
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