Volume 20 of Issue 3 | PLoS pathogens
Authors: Paredes MI, Perofsky AC, Frisbie L, Moncla LH, Roychoudhury P, Xie H, Bakhash SAM, Kong K, Arnould I, Nguyen TV, Wendm ST, Hajian P, Ellis S, Mathias PC, Greninger AL, Starita LM, Frazar CD, Ryke E, Zhong W, Gamboa L, Threlkeld M, Lee J, Stone J, McDermot E, Truong M, Shendure J, Oltean HN, Viboud C, Chu H, Müller NF, Bedford T
SARS-CoV-2 transmission is largely driven by heterogeneous dynamics at a local scale, leaving local health departments to design interventions with limited information. We analyzed SARS-CoV-2 genomes sampled between February 2020 and March 2022 jointly with epidemiological and cell phone mobility data to investigate fine scale spatiotemporal SARS-CoV-2 transmission dynamics in King County, Washington, a diverse, metropolitan US county. We applied an approximate structured coalescent approach to model transmission within and between North King County and South King County alongside the rate of outside introductions into the county. Our phylodynamic analyses reveal that following stay-at-home orders, the epidemic trajectories of North and South King County began to diverge. We find that South King County consistently had more reported and estimated cases, COVID-19 hospitalizations, and longer persistence of local viral transmission when compared to North King County, where viral importations from outside drove a larger proportion of new cases. Using mobility and demographic data, we also find that South King County experienced a more modest and less sustained reduction in mobility following stay-at-home orders than North King County, while also bearing more socioeconomic inequities that might contribute to a disproportionate burden of SARS-CoV-2 transmission. Overall, our findings suggest a role for local-scale phylodynamics in understanding the heterogeneous transmission landscape.
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Critical care (London, England)
Authors: Ceccato A, Forne C, Bos LD, Camprubí-Rimblas M, Areny-Balagueró A, Campaña-Duel E, Quero S, Diaz E, Roca O, De Gonzalo-Calvo D, Fernández-Barat L, Motos A, Ferrer R, Riera J, Lorente JA, Peñuelas O, Menendez R, Amaya-Villar R, Añón JM, Balan-Mariño A, Barberà C, Barberán J, Blandino-Ortiz A, Boado MV, Bustamante-Munguira E, Caballero J, Carbajales C, Carbonell N, Catalán-González M, Franco N, Galbán C, Gumucio-Sanguino VD, de la Torre MDC, Estella Á, Gallego E, García-Garmendia JL, Garnacho-Montero J, Gómez JM, Huerta A, Jorge-García RN, Loza-Vázquez A, Marin-Corral J, Martínez de la Gándara A, Martin-Delgado MC, Martínez-Varela I, Messa JL, Muñiz-Albaiceta G, Nieto MT, Novo MA, Peñasco Y, Pozo-Laderas JC, Pérez-García F, Ricart P, Roche-Campo F, Rodríguez A, Sagredo V, Sánchez-Miralles A, Sancho-Chinesta S, Socias L, Solé-Violan J, Suarez-Sipmann F, Tamayo-Lomas L, Trenado J, Úbeda A, Valdivia LJ, Vidal P, Bermejo J, Gonzalez J, Barbe F, Calfee CS, Artigas A, Torres A, CIBERESUCICOVID Project
Journal of thrombosis and haemostasis : JTH
Authors: Schulman S, Arnold DM, Bradbury CA, Broxmeyer L, Connors JM, Falanga A, Iba T, Kaatz S, Levy JH, Middeldorp S, Minichiello T, Nazy I, Ramacciotti E, Resnick HE, Samama CM, Sholzberg M, Thachil J, Zarychanski R, Spyropoulos AC, International Society on Thrombosis and Haemostasis
JMIR cardio
Authors: Park LG, Chi S, Pitsenbarger S, Johnson JK, Shah AJ, Elnaggar A, von Oppenfeld J, Cho E, Harzand A, Whooley MA
Volume 16 of Issue 738 | Science translational medicine
Authors: Westberg M, Su Y, Zou X, Huang P, Rustagi A, Garhyan J, Patel PB, Fernandez D, Wu Y, Hao C, Lo CW, Karim M, Ning L, Beck A, Saenkham-Huntsinger P, Tat V, Drelich A, Peng BH, Einav S, Tseng CK, Blish C, Lin MZ
Inhibitors of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (M) such as nirmatrelvir (NTV) and ensitrelvir (ETV) have proven effective in reducing the severity of COVID-19, but the presence of resistance-conferring mutations in sequenced viral genomes raises concerns about future drug resistance. Second-generation oral drugs that retain function against these mutants are thus urgently needed. We hypothesized that the covalent hepatitis C virus protease inhibitor boceprevir (BPV) could serve as the basis for orally bioavailable drugs that inhibit SARS-CoV-2 M more efficiently than existing drugs. Performing structure-guided modifications of BPV, we developed a picomolar-affinity inhibitor, ML2006a4, with antiviral activity, oral pharmacokinetics, and therapeutic efficacy similar or superior to those of NTV. A crucial feature of ML2006a4 is a derivatization of the ketoamide reactive group that improves cell permeability and oral bioavailability. Last, ML2006a4 was found to be less sensitive to several mutations that cause resistance to NTV or ETV and occur in the natural SARS-CoV-2 population. Thus, anticipatory design can preemptively address potential resistance mechanisms to expand future treatment options against coronavirus variants.
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Seminars in immunology
Authors: Peluso MJ, Abdel-Mohsen M, Henrich TJ, Roan NR
Nature communications
Authors: Park HJ, Gonsalves GS, Tan ST, Kelly JD, Rutherford GW, Wachter RM, Schechter R, Paltiel AD, Lo NC
Nature communications
Authors: Jaumdally S, Tomasicchio M, Pooran A, Esmail A, Kotze A, Meier S, Wilson L, Oelofse S, van der Merwe C, Roomaney A, Davids M, Suliman T, Joseph R, Perumal T, Scott A, Shaw M, Preiser W, Williamson C, Goga A, Mayne E, Gray G, Moore P, Sigal A, Limberis J, Metcalfe J, Dheda K
Annals of internal medicine
Authors: Paules CI, Wang J, Tomashek KM, Bonnett T, Singh K, Marconi VC, Davey RT, Lye DC, Dodd LE, Yang OO, Benson CA, Deye GA, Doernberg SB, Hynes NA, Grossberg R, Wolfe CR, Nayak SU, Short WR, Voell J, Potter GE, Rapaka RR
Critical care (London, England)
Authors: Alipanah-Lechner N, Hurst-Hopf J, Delucchi K, Swigart L, Willmore A, LaCombe B, Dewar R, Lane HC, Lallemand P, Liu KD, Esserman L, Matthay MA, Calfee CS, I-SPY COVID Consortium
