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2. A trivalent protein-based pan-Betacoronavirus vaccine elicits cross-neutralizing antibodies against a panel of coronavirus pseudoviruses

Author

Thimmiraju, Syamala Rani, Adhikari, Rakesh, Redd, JeAnna R., Villar, Maria Jose, Lee, Jungsoon, Liu, Zhuyun, Chen, Yi-Lin, Sharma, Suman, Kaur, Amandeep, Uzcategui, Nestor L., Ronca, Shannon E., Chen, Wen-Hsiang, Kimata, Jason T., Zhan, Bin, Strych, Ulrich, Bottazzi, Maria Elena, Hotez, Peter J., and Pollet, Jeroen

Published
2024
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3. Immunogenicity phase II study evaluating booster capacity of nonadjuvanted AKS-452 SARS-Cov-2 RBD Fc vaccine

Author

Alleva, David G., Feitsma, Eline A., Janssen, Yester F., Boersma, Hendrikus H., Lancaster, Thomas M., Sathiyaseelan, Thillainaygam, Murikipudi, Sylaja, Delpero, Andrea R., Scully, Melanie M., Ragupathy, Ramya, Kotha, Sravya, Haworth, Jeffrey R., Shah, Nishit J., Rao, Vidhya, Nagre, Shashikant, Ronca, Shannon E., Green, Freedom M., Shaw, Stephen A., Aminetzah, Ari, Kruijff, Schelto, Brom, Maarten, van Dam, Gooitzen M., and Zion, Todd C.

Published
2024
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4. Novel species of Triatoma (Hemiptera: Reduviidae) identified in a case of vectorial transmission of Chagas disease in northern Belize

Author

Gunter, Sarah M., Nelson, Alisa, Kneubehl, Alexander R., Justi, Silvia A., Manzanero, Russell, Zielinski-Gutierrez, Emily, Herrera, Claudia, Thompson, Julie, Mandage, Rajendra, Desale, Hans, Maliga, Adrianna, Bautista, Kim, Ronca, Shannon E., Morey, Francis, Fuentes, Rafael Chacon, Lopez, Beatriz, Dumonteil, Eric, Morazan, Gerhaldine H., and Murray, Kristy O.

Published
2024
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5. DNA-encoded chemistry technology yields expedient access to SARS-CoV-2 Mpro inhibitors

Author

Chamakuri, Srinivas, Lu, Shuo, Ucisik, Melek Nihan, Bohren, Kurt M, Chen, Ying-Chu, Du, Huang-Chi, Faver, John C, Jimmidi, Ravikumar, Li, Feng, Li, Jian-Yuan, Nyshadham, Pranavanand, Palmer, Stephen S, Pollet, Jeroen, Qin, Xuan, Ronca, Shannon E, Sankaran, Banumathi, Sharma, Kiran L, Tan, Zhi, Versteeg, Leroy, Yu, Zhifeng, Matzuk, Martin M, Palzkill, Timothy, and Young, Damian W

Subjects
Medicinal and Biomolecular Chemistry, Chemical Sciences, Vaccine Related, Lung, Infectious Diseases, Biodefense, Prevention, Emerging Infectious Diseases, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Good Health and Well Being, Animals, COVID-19, Cells, Cultured, Coronavirus 3C Proteases, Dose-Response Relationship, Drug, Drug Discovery, Enzyme Activation, Genetic Engineering, Humans, Models, Molecular, Molecular Conformation, Molecular Structure, Protease Inhibitors, SARS-CoV-2, Structure-Activity Relationship, Virus Replication, COVID-19 Drug Treatment, antiviral, covalent inhibitors, drug discovery
Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has killed more than 4 million humans globally, but there is no bona fide Food and Drug Administration-approved drug-like molecule to impede the COVID-19 pandemic. The sluggish pace of traditional therapeutic discovery is poorly suited to producing targeted treatments against rapidly evolving viruses. Here, we used an affinity-based screen of 4 billion DNA-encoded molecules en masse to identify a potent class of virus-specific inhibitors of the SARS-CoV-2 main protease (Mpro) without extensive and time-consuming medicinal chemistry. CDD-1714, the initial three-building-block screening hit (molecular weight [MW] = 542.5 g/mol), was a potent inhibitor (inhibition constant [Ki] = 20 nM). CDD-1713, a smaller two-building-block analog (MW = 353.3 g/mol) of CDD-1714, is a reversible covalent inhibitor of Mpro (Ki = 45 nM) that binds in the protease pocket, has specificity over human proteases, and shows in vitro efficacy in a SARS-CoV-2 infectivity model. Subsequently, key regions of CDD-1713 that were necessary for inhibitory activity were identified and a potent (Ki = 37 nM), smaller (MW = 323.4 g/mol), and metabolically more stable analog (CDD-1976) was generated. Thus, screening of DNA-encoded chemical libraries can accelerate the discovery of efficacious drug-like inhibitors of emerging viral disease targets.

Published
2021

6. Early cellular and molecular signatures correlate with severity of West Nile virus infection

Author

Lee, Ho-Joon, Zhao, Yujiao, Fleming, Ira, Mehta, Sameet, Wang, Xiaomei, Wyk, Brent Vander, Ronca, Shannon E., Kang, Heather, Chou, Chih-Hung, Fatou, Benoit, Smolen, Kinga K., Levy, Ofer, Clish, Clary B., Xavier, Ramnik J., Steen, Hanno, Hafler, David A., Love, J. Christopher, Shalek, Alex K., Guan, Leying, Murray, Kristy O., Kleinstein, Steven H., and Montgomery, Ruth R.

Published
2023
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10. DNA-encoded chemistry technology yields expedient access to SARS-CoV-2 M pro inhibitors

Author

Chamakuri, Srinivas, Lu, Shuo, Ucisik, Melek Nihan, Bohren, Kurt M., Chen, Ying-Chu, Du, Huang-Chi, Faver, John C., Jimmidi, Ravikumar, Li, Feng, Li, Jian-Yuan, Nyshadham, Pranavanand, Palmer, Stephen S., Pollet, Jeroen, Qin, Xuan, Ronca, Shannon E., Sankaran, Banumathi, Sharma, Kiran L., Tan, Zhi, Versteeg, Leroy, Yu, Zhifeng, Matzuk, Martin M., Palzkill, Timothy, and Young, Damian W.

Published
2021

11. West Nile Virus

Author

Gulas-Wroblewski, Bonnie E., Saldaña, Miguel A., Murray, Kristy O., Ronca, Shannon E., Hotez, Peter J., Series Editor, and Weatherhead, Jill E., editor

Published
2021
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12. Contributors

Author

Aboellail, Tawfik, primary, Abrahão, Jônatas Santos, additional, Adelino, Talita, additional, Akkina, Ramesh, additional, Alboudi, Ayman, additional, Alcantara, Luiz Carlos Junior, additional, Andersen, Henning, additional, Andrade, Teresinha De Jesus Aguiar Dos Santos, additional, Arakawa, Masashi, additional, de Araújo, Josélio Maria Galvão, additional, Azevedo, Pamella Nunes, additional, Bagasra, Omar, additional, Bailey, Mark J., additional, Baraklı, Serdar, additional, Basile, Alison Jane, additional, Bátiz, Luis Federico, additional, Bayrakci, Benan, additional, Bentes, Aline Almeida, additional, Bernatchez, Jean A., additional, Blázquez, A.B., additional, Borchardt-Lohölter, Viola, additional, Borges, Ana Luiza Vilela, additional, Burali, Maria Sole, additional, Bustamante-Barrientos, Felipe A., additional, Cabral Filho, Paulo E., additional, Cañas, Steven Vargas, additional, Castro, Talita, additional, Chang, Gwong-Jen J., additional, Chao, Day-Yu, additional, Chaudhari, Ameya, additional, Chaverra-Rodriguez, Duverney, additional, Christoff, Raissa R., additional, Coelho, Luiz Felipe Leomil, additional, Corrêa, Diogo Goulart, additional, Coste, Michael, additional, Coutinho, Raquel Zanatta, additional, da Costa Júnior, Joaquim Soares, additional, da Cunha Pereira, Anna Carolina Toledo, additional, da Matta Guedes, Paulo Marcos, additional, da Silva, Guilherme Liberato, additional, DaCosta, Jaderson Costa, additional, Dandekar, Prajakta, additional, Danielli, Amos, additional, das Dores Alves de Oliveira, Maria, additional, Deniz, Orhan, additional, Desprès, Philippe, additional, Drumond, Betânia Paiva, additional, Duque, Jonny, additional, e Silva Alves, Patrícia, additional, El Kalamouni, Chaker, additional, Fernandes, José Veríssimo, additional, Ferreira, Gustavo Portela, additional, Foiadelli, T., additional, Fonseca, Vagner, additional, Fontes, Adriana, additional, Frenkel, Lawrence, additional, Gadea, Gilles, additional, Garcez, Patricia P., additional, Giovanetti, Marta, additional, Gomez, Fernando, additional, Gulas-Wroblewski, Bonnie E., additional, Gümüşyayla, Şadiye, additional, Gurung, Sunam, additional, Haddad, Juliano G., additional, Harbo, Thomas, additional, Hedin-Pereira, Cecília, additional, Henzi, Roberto, additional, Hughes, Holly R., additional, Hygino da Cruz Júnior, Luiz Celso, additional, Jameson, Andrew, additional, Jordan, Rachel, additional, Kairis, Rebecca B., additional, Kaura, Taruna, additional, Kesici, Selman, additional, Khazali, Ahmad Suhail, additional, Klemens, Julia Maria, additional, Kroon, Erna Geessien, additional, Lam, Walter Sze Tung, additional, Lattwein, Erik, additional, Lazarev, Vladimir V., additional, Leite, Túlio César Rodrigues, additional, Li, Cui, additional, Lima, Nerilson Marques, additional, Lopes Moreira, Maria Elizabeth, additional, Loza, Karina Carrillo, additional, Machado, Denise Cantarelli, additional, Majolo, Fernanda, additional, Malaquias, Luiz Cosme Cotta, additional, Manfroni, Giuseppe, additional, Marinowic, Daniel Rodrigo, additional, Marques Abramov, Dimitri, additional, Marseglia, G.L., additional, McLean, Ewen, additional, de Mello Silva, Breno, additional, Mendez-Sanchez, Stelia, additional, Mewara, Abhishek, additional, Morita, Eiji, additional, Murray, Kristy O., additional, Myers, Dean, additional, Nascimento, Manuela Sales Lima, additional, Nascimento, Osvaldo J.M., additional, Paes, Marciano Viana, additional, Papin, James, additional, Pereira, Giovannia A.L., additional, Pereira, Goreti, additional, Pereira, Maria I.A., additional, Pervaiz, Naveed, additional, Purse, Byron W., additional, Rabelo, Kíssila, additional, Ribeiro, Jéssika F.F., additional, Ronca, Shannon E., additional, Roth, Shira, additional, Saad Salles, Tania Regina, additional, Sacchetto, Lívia, additional, Saiz, J.C., additional, Salomão, Natália Gedeão, additional, Santos, Beate S., additional, Saschenbrecker, Sandra, additional, Savasta, S., additional, Schlumberger, Wolfgang, additional, Schmitt, Kimberly, additional, Siqueira-Neto, Jair L., additional, Soon, Derek Tuck Loong, additional, Soto-Hernández, José Luis, additional, de Souza, Gabriel Augusto Pires, additional, Steinhagen, Katja, additional, Stiba, Konstanze, additional, Tambyah, Paul Ananth, additional, Tan, Gene S., additional, Tosta, Stephane, additional, Trabatti, C., additional, Vural, Gönül, additional, Werner, Heron, additional, Xavier, Joilson, additional, Xu, Zhiheng, additional, Xuan, Tay Wei, additional, and Yusof, Rohana, additional

Published
2022
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13. Seroprevalence of Anti-SARS-CoV-2 IgG Antibodies in Healthcare Personnel in El Salvador Prior to Vaccination Campaigns.

Author

Ramírez, José Elías Aguilar, Maliga, Adrianna, Stewart, Allison, Lino, Allison, Oliva, José Eduardo, Sandoval, Xochitl, Zielinski-Gutierrez, Emily, Chacon-Fuentes, Rafael, Suchdev, Parminder S., Zelaya, Susana, Sánchez, Mario, Recinos, Delmy Lisseth, López, Beatriz, Hawes, Ella, Liu, Julie, Ronca, Shannon E., Gunter, Sarah M., Murray, Kristy O., and Domínguez, Rhina

Subjects
MEDICAL personnel, EMERGING infectious diseases, SEROPREVALENCE, SARS-CoV-2, IMMUNOGLOBULIN G
Abstract

COVID-19, caused by the SARS-CoV-2 virus, is a highly pathogenic emerging infectious disease. Healthcare personnel (HCP) are presumably at higher risk of acquiring emerging infections because of occupational exposure. The prevalence of COVID-19 in HCP is unknown, particularly in low- to middle-income countries like El Salvador. The goal of this study was to determine the seroprevalence of anti-SARS-CoV-2 antibodies among HCP in El Salvador just prior to vaccine rollout in March 2021. We evaluated 2176 participants from a nationally representative sample of national healthcare institutions. We found 40.4% (n = 880) of the study participants were seropositive for anti-spike protein antibodies. Significant factors associated with infection included younger age; living within the central, more populated zone of the country; living in a larger household (≥7 members); household members with COVID-19 or compatible symptoms; and those who worked in auxiliary services (i.e., housekeeping and food services). These findings provide insight into opportunities to mitigate SARS-CoV-2 risk and other emerging respiratory pathogens in HCP in El Salvador. [ABSTRACT FROM AUTHOR]

Published
2024
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18. A randomized phase I/II safety and immunogenicity study of the Montanide-adjuvanted SARS-CoV-2 spike protein-RBD-Fc vaccine, AKS-452

Author

Feitsma, Eline A., Janssen, Yester F., Boersma, Hendrikus H., van Sleen, Yannick, van Baarle, Debbie, Alleva, David G., Lancaster, Thomas M., Sathiyaseelan, Thillainaygam, Murikipudi, Sylaja, Delpero, Andrea R., Scully, Melanie M., Ragupathy, Ramya, Kotha, Sravya, Haworth, Jeffrey R., Shah, Nishit J., Rao, Vidhya, Nagre, Shashikant, Ronca, Shannon E., Green, Freedom M., Aminetzah, Ari, Sollie, Frans, Kruijff, Schelto, Brom, Maarten, van Dam, Gooitzen M., Zion, Todd C., Translational Immunology Groningen (TRIGR), Guided Treatment in Optimal Selected Cancer Patients (GUTS), ​Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE), and Microbes in Health and Disease (MHD)

Subjects
Fc-fusion, Infectious disease, General Veterinary, General Immunology and Microbiology, Pandemic, Prophylaxis, SARS-CoV-2, Public Health, Environmental and Occupational Health, COVID-19, AKS-452, Phase 2, Coronavirus, Infectious Diseases, Molecular Medicine, Vaccine
Abstract

Background: Previous interim data from a phase I study of AKS-452, a subunit vaccine comprising an Fc fusion of the respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein receptor binding domain (SP/RBD) emulsified in the water-in-oil adjuvant, Montanide™ ISA 720, suggested a good safety and immunogenicity profile in healthy adults. This phase I study was completed and two dosing regimens were further evaluated in this phase II study.Methods: This phase II randomized, open-labelled, parallel group study was conducted at a single site in The Netherlands with 52 healthy adults (18 – 72 years) receiving AKS-452 subcutaneously at one 90 µg dose (cohort 1, 26 subjects) or two 45 µg doses 28 days apart (cohort 2, 26 subjects). Serum samples were collected at the first dose (day 0) and at days 28, 56, 90, and 180. Safety and immunogenicity endpoints were assessed, along with induction of IgG isotypes, cross-reactive immunity against viral variants, and IFN-γ T cell responses.Results: All AEs were mild/moderate (grades 1 or 2), and no SAEs were attributable to AKS-452. Seroconversion rates reached 100% in both cohorts, although cohort 2 showed greater geometric mean IgG titers that were stable through day 180 and associated with enhanced potencies of SP/RBD-ACE2 binding inhibition and live virus neutralization. AKS-452-induced IgG titers strongly bound mutant SP/RBD from several SARS-CoV-2 variants (including Omicrons) that were predominantly of the favorable IgG1/3 isotype and IFN-γ-producing T cell phenotype.Conclusion: These favorable safety and immunogenicity profiles of the candidate vaccine as demonstrated in this phase II study are consistent with those of the phase I study (ClinicalTrials.gov: NCT04681092) and suggest that a total of 90 µg received in 2 doses may offer a greater duration of cross-reactive neutralizing titers than when given in a single dose.

Published
2023

20. Early cellular and molecular signatures correlate with severity of West Nile Virus infection

Author

Lee, Ho-Joon, primary, Zhao, Yujiao, additional, Fleming, Ira, additional, Mehta, Sameet, additional, Wang, Xiaomei, additional, Wyk, Brent Vander, additional, Ronca, Shannon E., additional, Kang, Heather, additional, Chou, Chih-Hung, additional, Fatou, Benoit, additional, Smolen, Kinga K., additional, Levy, Ofer, additional, Clish, Clary B., additional, Xavier, Ramnik J., additional, Steen, Hanno, additional, Hafler, David A., additional, Love, J. Christopher, additional, Shalek, Alex K., additional, Guan, Leying, additional, Murray, Kristy O., additional, Kleinstein, Steven H., additional, and Montgomery, Ruth R., additional

Published
2023
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22. Cumulative Incidence of West Nile Virus Infection, Continental United States, 1999-2016

Author

Ronca, Shannon E., Murray, Kristy O., and Nolan, Melissa S.

Subjects
West Nile fever -- Health aspects, Infection -- Health aspects, Disease transmission -- Health aspects, Mosquitoes, Cognitive disorders, Encephalitis, Meningitis, Public health, Health, Paralysis, Medical schools, Health
Abstract

West Nile virus (WNV) is a mosquito-transmitted flavivirus with human health implications. Since its emergence in 1999, WNV has become endemic across the continental United States (1). Seasonal outbreaks occur [...]

Published
2019
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23. Longitudinal serum proteomics analyses identify unique and overlapping host response pathways in Lyme disease and West Nile virus infection

Author

Boada, Patrick, primary, Fatou, Benoit, additional, Belperron, Alexia A., additional, Sigdel, Tara K., additional, Smolen, Kinga K., additional, Wurie, Zainab, additional, Levy, Ofer, additional, Ronca, Shannon E., additional, Murray, Kristy O., additional, Liberto, Juliane M., additional, Rashmi, Priyanka, additional, Kerwin, Maggie, additional, Montgomery, Ruth R., additional, Bockenstedt, Linda K., additional, Steen, Hanno, additional, and Sarwal, Minnie M., additional

Published
2022
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24. Diagnosis of Acute Chagas Disease in a Belizean Child with Evidence of a Multiclonal Trypanosoma cruzi Infection

Author

Murray, Kristy O., primary, Saldaña, Miguel A., additional, Gunter, Sarah M., additional, Manzanero, Russell, additional, Zielinski-Gutierrez, Emily, additional, Herrera, Claudia, additional, Thompson, Julie M., additional, Maliga, Adrianna, additional, Bautista, Kim, additional, Lino, Allison, additional, Hawes, Ella, additional, Ronca, Shannon E., additional, Morey, Francis, additional, Fuentes, Rafael Chacon, additional, Lopez, Beatriz, additional, Dumonteil, Eric, additional, and Morazan, Gerhaldine H., additional

Published
2022
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27. Vector-borne diseases of public health importance for personnel on military installations in the United States

Author

Garcia, Melissa N., Cropper, Thomas L., Gunter, Sarah M., Kramm, Mathew M., Pawlak, Mary T., Roachell, Walter, Ronca, Shannon E., Stidham, Ralph A., Webber, Bryant J., and Yun, Heather C.

Subjects
United States. Department of Defense -- Standards, United States. Centers for Disease Control and Prevention -- Standards, Military personnel -- Care and treatment, Disease transmission -- Prevention, Medical research, Military bases -- Usage, Health
Abstract

Vector-borne diseases (VBDs) are among the leading causes of morbidity and mortality worldwide. The history of US military medicine dates from the formation of the Continental Army in the 1770s. [...]

Published
2017

32. Epidemiological and Clinical Characteristics of Acute Dengue Virus Infections Detected through Acute Febrile Illness Surveillance, Belize 2020

Author

Ly, Anh N., primary, Manzanero, Russell, additional, Maliga, Adrianna, additional, Gunter, Sarah M., additional, Ronca, Shannon E., additional, Zielinski-Gutierrez, Emily, additional, Morey, Francis, additional, Bautista, Kim, additional, Espinosa-Bode, Andres, additional, López, Beatriz, additional, Cadena, Loren, additional, Fuentes, Rafael C., additional, Erickson, Timothy A., additional, Munoz, Flor M., additional, Mackey, Joy, additional, Morazán, Gerhaldine, additional, and Murray, Kristy O., additional

Published
2022
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33. From concept to delivery: a yeast-expressed recombinant protein-based COVID-19 vaccine technology suitable for global access.

Author

Hotez, Peter J., Adhikari, Rakesh, Chen, Wen-Hsiang, Chen, Yi-Lin, Gillespie, Portia, Islam, Nelufa Y., Keegan, Brian, Tyagi Kundu, Rakhi, Lee, Jungsoon, Liu, Zhuyun, Kimata, Jason T., Oezguen, Numan, Pollet, Jeroen, Poveda, Cristina, Razavi, Kay, Ronca, Shannon E., Strych, Ulrich, Thimmiraju, Syamala R., Versteeg, Leroy, and Villar-Mondragon, Maria Jose

Subjects
COVID-19 vaccines, VACCINATION, EMERGING infectious diseases, RECOMBINANT proteins, GENE expression
Abstract

The development of a yeast-expressed recombinant protein-based vaccine technology co-developed with LMIC vaccine producers and suitable as a COVID-19 vaccine for global access is described. The proof-of-concept for developing a SARS-CoV-2 spike protein receptor-binding domain (RBD) antigen as a yeast-derived recombinant protein vaccine technology is described. Genetic Engineering: The strategy is presented for the design and genetic modification used during cloning and expression in the yeast system. Process and Assay Development: A summary is presented of how a scalable, reproducible, and robust production process for the recombinant protein COVID-19 vaccine antigen was developed. Formulation and Pre-clinical Strategy: We report on the pre-clinical and formulation strategy used for the proof-of-concept evaluation of the SARS-CoV-2 RBD vaccine antigen. Technology Transfer and Partnerships: The process used for the technology transfer and co-development with LMIC vaccine producers is described. Clinical Development and Delivery: The approach used by LMIC developers to establish the industrial process, clinical development, and deployment is described. Highlighted is an alternative model for developing new vaccines for emerging infectious diseases of pandemic importance starting with an academic institution directly transferring their technology to LMIC vaccine producers without the involvement of multinational pharma companies. [ABSTRACT FROM AUTHOR]

Published
2023
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34. Phase I interim results of a phase I/II study of the IgG-Fc fusion COVID-19 subunit vaccine, AKS-452

Author

Janssen, Yester F., primary, Feitsma, Eline A., additional, Boersma, Hendrikus H., additional, Alleva, David G., additional, Lancaster, Thomas M., additional, Sathiyaseelan, Thillainaygam, additional, Murikipudi, Sylaja, additional, Delpero, Andrea R., additional, Scully, Melanie M., additional, Ragupathy, Ramya, additional, Kotha, Sravya, additional, Haworth, Jeffrey R., additional, Shah, Nishit J., additional, Rao, Vidhya, additional, Nagre, Shashikant, additional, Ronca, Shannon E., additional, Green, Freedom M., additional, Aminetzah, Ari, additional, Sollie, Frans, additional, Kruijff, Schelto, additional, Brom, Maarten, additional, van Dam, Gooitzen M., additional, and Zion, Todd C., additional

Published
2022
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35. Incorporating COVID-19 into Acute Febrile Illness Surveillance Systems, Belize, Kenya, Ethiopia, Peru, and Liberia, 2020–2021

Author

Shih, David C., primary, Silver, Rachel, additional, Henao, Olga L., additional, Alemu, Aynalem, additional, Audi, Allan, additional, Bigogo, Godfrey, additional, Colston, Josh M., additional, Edu-Quansah, Elijah P., additional, Erickson, Timothy A., additional, Gashu, Andargachew, additional, Gbelee, G. Burgess, additional, Gunter, Sarah M., additional, Kosek, Margaret N., additional, Logan, Gorbee G., additional, Mackey, Joy M., additional, Maliga, Adrianna, additional, Manzanero, Russell, additional, Morazan, Gerhaldine, additional, Morey, Francis, additional, Munoz, Flor M., additional, Murray, Kristy O., additional, Nelson, Thelma V., additional, Olortegui, Maribel Paredes, additional, Yori, Pablo Penataro, additional, Ronca, Shannon E., additional, Schiaffino, Francesca, additional, Tayachew, Adamu, additional, Tedasse, Musse, additional, Wossen, Mesfin, additional, Allen, Denise R., additional, Angra, Pawan, additional, Balish, Amanda, additional, Farron, Madeline, additional, Guerra, Marta, additional, Herman-Roloff, Amy, additional, Hicks, Victoria J., additional, Hunsperger, Elizabeth, additional, Kazazian, Lilit, additional, Mikoleit, Matt, additional, Munyua, Peninah, additional, Munywoki, Patrick K., additional, Namwase, Angella Sandra, additional, Onyango, Clayton O., additional, Park, Michael, additional, Peruski, Leonard F., additional, Sugerman, David E., additional, Gutierrez, Emily Zielinski, additional, and Cohen, Adam L., additional

Published
2022
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37. Development of an IgG-Fc fusion COVID-19 subunit vaccine, AKS-452

Author

Alleva, David G., primary, Delpero, Andrea R., additional, Scully, Melanie M., additional, Murikipudi, Sylaja, additional, Ragupathy, Ramya, additional, Greaves, Emma K., additional, Sathiyaseelan, Thillainaygam, additional, Haworth, Jeffrey R., additional, Shah, Nishit J., additional, Rao, Vidhya, additional, Nagre, Shashikant, additional, Lancaster, Thomas M., additional, Webb, Sarah S., additional, Jasa, Allison I., additional, Ronca, Shannon E., additional, Green, Freedom M., additional, Elyard, Hanne Andersen, additional, Yee, JoAnn, additional, Klein, Jeffrey, additional, Karnes, Larry, additional, Sollie, Frans, additional, and Zion, Todd C., additional

Published
2021
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42. DNA-encoded chemistry technology yields expedient access to SARS-CoV-2 Mpro inhibitors.

Author

Chamakuri, Srinivas, Shuo Lu, Ucisik, Melek Nihan, Bohren, Kurt M., Ying-Chu Chen, Huang-Chi Du, Faver, John C., Jimmidi, Ravikumar, Feng Li, Jian-Yuan Li, Nyshadham, Pranavanand, Palmer, Stephen S., Pollet, Jeroen, Xuan Qin, Ronca, Shannon E., Sankaran, Banumathi, Sharma, Kiran L., Zhi Tan, Versteeg, Leroy, and Zhifeng Yu

Subjects
SARS-CoV-2, CHEMICAL yield, COVID-19 pandemic, VIRUS diseases, CHEMICAL libraries
Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has killed more than 4 million humans globally, but there is no bona fide Food and Drug Administration-approved drug-like molecule to impede the COVID-19 pandemic. The sluggish pace of traditional therapeutic discovery is poorly suited to producing targeted treatments against rapidly evolving viruses. Here, we used an affinity-based screen of 4 billion DNA-encoded molecules en masse to identify a potent class of virus-specific inhibitors of the SARS-CoV-2 main protease (Mpro) without extensive and time-consuming medicinal chemistry. CDD-1714, the initial three-building-block screening hit (molecular weight [MW] = 542.5 g/mol), was a potent inhibitor (inhibition constant [Ki] = 20 nM). CDD-1713, a smaller two-building-block analog (MW = 353.3 g/mol) of CDD-1714, is a reversible covalent inhibitor of Mpro (Ki = 45 nM) that binds in the protease pocket, has specificity over human proteases, and shows in vitro efficacy in a SARS-CoV-2 infectivity model. Subsequently, key regions of CDD-1713 that were necessary for inhibitory activity were identified and a potent (Ki = 37 nM), smaller (MW = 323.4 g/mol), and metabolically more stable analog (CDD-1976) was generated. Thus, screening of DNA-encoded chemical libraries can accelerate the discovery of efficacious drug-like inhibitors of emerging viral disease targets. [ABSTRACT FROM AUTHOR]

Published
2021
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