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327 results on '"Lindenbach, Brett"'

1. SARS-CoV-2-related bat viruses evade human intrinsic immunity but lack efficient transmission capacity

Author

Peña-Hernández, Mario A., Alfajaro, Mia Madel, Filler, Renata B., Moriyama, Miyu, Keeler, Emma L., Ranglin, Zara E., Kong, Yong, Mao, Tianyang, Menasche, Bridget L., Mankowski, Madeleine C., Zhao, Zhe, Vogels, Chantal B. F., Hahn, Anne M., Kalinich, Chaney C., Zhang, Shuo, Huston, Nicholas, Wan, Han, Araujo-Tavares, Rafael, Lindenbach, Brett D., Homer, Robert, Pyle, Anna Marie, Martinez, David R., Grubaugh, Nathan D., Israelow, Benjamin, Iwasaki, Akiko, and Wilen, Craig B.

Published
2024
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2. Virology—the path forward

Author

Rasmussen, Angela L, Gronvall, Gigi K, Lowen, Anice C, Goodrum, Felicia, Alwine, James, Andersen, Kristian G, Anthony, Simon J, Baines, Joel, Banerjee, Arinjay, Broadbent, Andrew J, Brooke, Christopher B, Campos, Samuel K, Caposio, Patrizia, Casadevall, Arturo, Chan, Gary C, Cliffe, Anna R, Collins-McMillen, Donna, Connell, Nancy, Damania, Blossom, Daugherty, Matthew D, Debbink, Kari, Dermody, Terence S, DiMaio, Daniel, Duprex, W Paul, Emerman, Michael, Galloway, Denise A, Garry, Robert F, Goldstein, Stephen A, Greninger, Alexander L, Hartman, Amy L, Hogue, Brenda G, Horner, Stacy M, Hotez, Peter J, Jung, Jae U, Kamil, Jeremy P, Karst, Stephanie M, Laimins, Lou, Lakdawala, Seema S, Landais, Igor, Letko, Michael, Lindenbach, Brett, Liu, Shan-Lu, Luftig, Micah, McFadden, Grant, Mehle, Andrew, Morrison, Juliet, Moscona, Anne, Mühlberger, Elke, Munger, Joshua, Münger, Karl, Murphy, Eain, Neufeldt, Christopher J, Nikolich, Janko Z, O'Connor, Christine M, Pekosz, Andrew, Permar, Sallie R, Pfeiffer, Julie K, Popescu, Saskia V, Purdy, John G, Racaniello, Vincent R, Rice, Charles M, Runstadler, Jonathan A, Sapp, Martin J, Scott, Rona S, Smith, Gregory A, Sorrell, Erin M, Speranza, Emily, Streblow, Daniel, Tibbetts, Scott A, Toth, Zsolt, Van Doorslaer, Koenraad, Weiss, Susan R, White, Elizabeth A, White, Timothy M, Wobus, Christiane E, Worobey, Michael, Yamaoka, Satoko, and Yurochko, Andrew

Subjects
Agricultural, Veterinary and Food Sciences, Biological Sciences, Biomedical and Clinical Sciences, Emerging Infectious Diseases, Infectious Diseases, Prevention, Coronaviruses, Good Health and Well Being, Humans, Containment of Biohazards, COVID-19, United States, Viruses, Virology, Biomedical Research, virology, SARS-CoV-2, oversight, biosafety, emergence, Agricultural and Veterinary Sciences, Medical and Health Sciences, Agricultural, veterinary and food sciences, Biological sciences, Biomedical and clinical sciences
Abstract

In the United States (US), biosafety and biosecurity oversight of research on viruses is being reappraised. Safety in virology research is paramount and oversight frameworks should be reviewed periodically. Changes should be made with care, however, to avoid impeding science that is essential for rapidly reducing and responding to pandemic threats as well as addressing more common challenges caused by infectious diseases. Decades of research uniquely positioned the US to be able to respond to the COVID-19 crisis with astounding speed, delivering life-saving vaccines within a year of identifying the virus. We should embolden and empower this strength, which is a vital part of protecting the health, economy, and security of US citizens. Herein, we offer our perspectives on priorities for revised rules governing virology research in the US.

Published
2024

3. Astrovirus replication is dependent on induction of double-membrane vesicles through a PI3K-dependent, LC3-independent pathway

Author

Bub, Theresa, Hargest, Virginia, Tan, Shaoyuan, Smith, Maria, Vazquez-Pagan, Ana, Flerlage, Tim, Brigleb, Pamela, Meliopoulos, Victoria, Lindenbach, Brett, Ramanathan, Harish N, Cortez, Valerie, Crawford, Jeremy Chase, and Schultz-Cherry, Stacey

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Biological Sciences, Infectious Diseases, Aetiology, 2.1 Biological and endogenous factors, Infection, Humans, Autophagy, Class III Phosphatidylinositol 3-Kinases, Intracellular Membranes, Organelles, Phosphatidylinositol 3-Kinase, RNA Viruses, Virus Replication, Mamastrovirus, Signal Transduction, astrovirus, autophagy, class III PI3K, double-membrane vesicle, replication organelle, Agricultural and Veterinary Sciences, Medical and Health Sciences, Virology, Agricultural, veterinary and food sciences, Biological sciences, Biomedical and clinical sciences
Abstract

Human astrovirus is a positive-sense, single-stranded RNA virus. Astrovirus infection causes gastrointestinal symptoms and can lead to encephalitis in immunocompromised patients. Positive-strand RNA viruses typically utilize host intracellular membranes to form replication organelles, which are potential antiviral targets. Many of these replication organelles are double-membrane vesicles (DMVs). Here, we show that astrovirus infection leads to an increase in DMV formation through a replication-dependent mechanism that requires some early components of the autophagy machinery. Results indicate that the upstream class III phosphatidylinositol 3-kinase (PI3K) complex, but not LC3 conjugation machinery, is utilized in DMV formation. Both chemical and genetic inhibition of the PI3K complex lead to significant reduction in DMVs, as well as viral replication. Elucidating the role of autophagy machinery in DMV formation during astrovirus infection reveals a potential target for therapeutic intervention for immunocompromised patients. IMPORTANCE These studies provide critical new evidence that astrovirus replication requires formation of double-membrane vesicles, which utilize class III phosphatidylinositol 3-kinase (PI3K), but not LC3 conjugation autophagy machinery, for biogenesis. These results are consistent with replication mechanisms for other positive-sense RNA viruses suggesting that targeting PI3K could be a promising therapeutic option for not only astrovirus, but other positive-sense RNA virus infections.

Published
2023

4. De novo emergence of a remdesivir resistance mutation during treatment of persistent SARS-CoV-2 infection in an immunocompromised patient: a case report

Author

Gandhi, Shiv, Klein, Jonathan, Robertson, Alexander J., Peña-Hernández, Mario A., Lin, Michelle J., Roychoudhury, Pavitra, Lu, Peiwen, Fournier, John, Ferguson, David, Mohamed Bakhash, Shah A. K., Catherine Muenker, M., Srivathsan, Ariktha, Wunder, Jr, Elsio A., Kerantzas, Nicholas, Wang, Wenshuai, Lindenbach, Brett, Pyle, Anna, Wilen, Craig B., Ogbuagu, Onyema, Greninger, Alexander L., Iwasaki, Akiko, Schulz, Wade L., and Ko, Albert I.

Published
2022
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6. Proof-of-concept studies with a computationally designed M pro inhibitor as a synergistic combination regimen alternative to Paxlovid

Author

Papini, Christina, primary, Ullah, Irfan, additional, Ranjan, Amalendu P., additional, Zhang, Shuo, additional, Wu, Qihao, additional, Spasov, Krasimir A., additional, Zhang, Chunhui, additional, Mothes, Walther, additional, Crawford, Jason M., additional, Lindenbach, Brett D., additional, Uchil, Pradeep D., additional, Kumar, Priti, additional, Jorgensen, William L., additional, and Anderson, Karen S., additional

Published
2024
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8. Correction for Rasmussen et al., “Virology—the path forward”

Author

Rasmussen, Angela L., primary, Gronvall, Gigi K., additional, Lowen, Anice C., additional, Goodrum, Felicia, additional, Alwine, James, additional, Andersen, Kristian G., additional, Anthony, Simon J., additional, Baines, Joel, additional, Banerjee, Arinjay, additional, Broadbent, Andrew J., additional, Brooke, Christopher B., additional, Campos, Samuel K., additional, Caposio, Patrizia, additional, Casadevall, Arturo, additional, Chan, Gary C., additional, Cliffe, Anna R., additional, Collins-McMillen, Donna, additional, Connell, Nancy, additional, Damania, Blossom, additional, Daugherty, Matthew D., additional, Debbink, Kari, additional, Dermody, Terence S., additional, DiMaio, Daniel, additional, Duprex, W. Paul, additional, Emerman, Michael, additional, Galloway, Denise A., additional, Garry, Robert F., additional, Goldstein, Stephen A., additional, Greninger, Alexander L., additional, Hartman, Amy L., additional, Hogue, Brenda G., additional, Horner, Stacy M., additional, Hotez, Peter J., additional, Jung, Jae U., additional, Kamil, Jeremy P., additional, Karst, Stephanie M., additional, Laimins, Lou, additional, Lakdawala, Seema S., additional, Landais, Igor, additional, Letko, Michael, additional, Lindenbach, Brett, additional, Liu, Shan-Lu, additional, Luftig, Micah, additional, McFadden, Grant, additional, Mehle, Andrew, additional, Morrison, Juliet, additional, Moscona, Anne, additional, Mühlberger, Elke, additional, Munger, Joshua, additional, Münger, Karl, additional, Murphy, Eain, additional, Neufeldt, Christopher J., additional, Nikolich, Janko Z., additional, O'Connor, Christine M., additional, Pekosz, Andrew, additional, Permar, Sallie R., additional, Pfeiffer, Julie K., additional, Popescu, Saskia V., additional, Purdy, John G., additional, Racaniello, Vincent R., additional, Rice, Charles M., additional, Runstadler, Jonathan A., additional, Sapp, Martin J., additional, Scott, Rona S., additional, Smith, Gregory A., additional, Sorrell, Erin M., additional, Speranza, Emily, additional, Streblow, Daniel, additional, Tibbetts, Scott A., additional, Toth, Zsolt, additional, Van Doorslaer, Koenraad, additional, Weiss, Susan R., additional, White, Elizabeth A., additional, White, Timothy M., additional, Wobus, Christiane E., additional, Worobey, Michael, additional, Yamaoka, Satoko, additional, and Yurochko, Andrew, additional

Published
2024
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12. Proof-of-concept studies with a computationally designed Mpro inhibitor as a synergistic combination regimen alternative to Paxlovid.

Author

Papini, Christina, Ullah, Irfan, Ranjan, Amalendu P., Shuo Zhang, Qihao Wu, Spasov, Krasimir A., Chunhui Zhang, Mothes, Walther, Crawford, Jason M., Lindenbach, Brett D., Uchil, Pradeep D., Kumar, Priti, Jorgensen, William L., and Anderson, Karen S.

Subjects
COVID-19 treatment, IMMUNOCOMPROMISED patients, PROOF of concept, LEAD compounds, ANTIVIRAL agents, DRUG interactions, FIREPROOFING agents
Abstract

As the SARS-CoV-2 virus continues to spread and mutate, it remains important to focus not only on preventing spread through vaccination but also on treating infection with direct-acting antivirals (DAA). The approval of Paxlovid, a SARS-CoV-2 main protease (Mpro) DAA, has been significant for treatment of patients. A limitation of this DAA, however, is that the antiviral component, nirmatrelvir, is rapidly metabolized and requires inclusion of a CYP450 3A4 metabolic inhibitor, ritonavir, to boost levels of the active drug. Serious drug-drug interactions can occur with Paxlovid for patients who are also taking other medications metabolized by CYP4503A4, particularly transplant or otherwise immunocompromised patients who are most at risk for SARS-CoV-2 infection and the development of severe symptoms. Developing an alternative antiviral with improved pharmacological properties is critical for treatment of these patients. By using a computational and structure-guided approach, we were able to optimize a 100 to 250 µM screening hit to a potent nanomolar inhibitor and lead compound, Mpro61. In this study, we further evaluate Mpro61 as a lead compound, starting with examination of its mode of binding to SARS-CoV-2 Mpro. In vitro pharmacological profiling established a lack of off-target effects, particularly CYP450 3A4 inhibition, as well as potential for synergy with the currently approved alternate antiviral, molnupiravir. Development and subsequent testing of a capsule formulation for oral dosing of Mpro61 in B6-K18-hACE2 mice demonstrated favorable pharmacological properties, efficacy, and synergy with molnupiravir, and complete recovery from subsequent challenge by SARS-CoV-2, establishing Mpro61 as a promising potential preclinical candidate. [ABSTRACT FROM AUTHOR]

Published
2024
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14. Positive‐strand RNA viruses—a Keystone Symposia report

Author

Cable, Jennifer, Denison, Mark R., Kielian, Margaret, Jackson, William T., Bartenschlager, Ralf, Ahola, Tero, Mukhopadhyay, Suchetana, Fremont, Daved H., Kuhn, Richard J., Shannon, Ashleigh, Frazier, Meredith N., Yuen, Kwok-Yung, Coyne, Carolyn B., Wolthers, Katja C., Ming, Guo-Li, Guenther, Camy S., Moshiri, Jasmine, Best, Sonja M., Schoggins, John W., Jurado, Kellie Ann, Ebel, Gregory D., Schäfer, Alexandra, Ng, Lisa F. P., Kikkert, Marjolein, Sette, Alessandro, Harris, Eva, Wing, Peter A. C., Eggenberger, Julie, Krishnamurthy, Siddharth R., Mah, Marcus G., Meganck, Rita M., Chung, Donghoon, Maurer-Stroh, Sebastian, Andino, Raul, Korber, Bette, Perlman, Stanley, Shi, Pei-Yong, Bárcena, Montserrat, Aicher, Sophie-Marie, Vu, Michelle N., Kenney, Devin J., Lindenbach, Brett D., Nishida, Yukiko, Rénia, Laurent, Williams, Evan P., Medical Microbiology and Infection Prevention, and AII - Infectious diseases

Subjects
RNA virus, flavivirus, History and Philosophy of Science, enterovirus, SARS-CoV-2, General Neuroscience, coronavirus, alphavirus, General Biochemistry, Genetics and Molecular Biology
Abstract

Positive-strand RNA viruses have been the cause of several recent outbreaks and epidemics, including the Zika virus epidemic in 2015, the SARS outbreak in 2003, and the ongoing SARS-CoV-2 pandemic. On June 18-22, 2022, researchers focusing on positive-strand RNA viruses met for the Keystone Symposium "Positive-Strand RNA Viruses" to share the latest research in molecular and cell biology, virology, immunology, vaccinology, and antiviral drug development. This report presents concise summaries of the scientific discussions at the symposium.

Published
2023
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15. Complete Replication of Hepatitis C Virus in Cell Culture

Author

Lindenbach, Brett D., Evans, Matthew J., Syder, Andrew J., Wölk, Benno, Tellinghuisen, Timothy L., Liu, Christopher C., Maruyama, Toshiaki, Hynes, Richard O., Burton, Dennis R., McKeating, Jane A., and Rice, Charles M.

Published
2005

19. Astrovirus replication is dependent on induction of double membrane vesicles through a PI3K-dependent, LC3-independent pathway

Author

Bub, Theresa, primary, Hargest, Virginia, additional, Tan, Shaoyuan, additional, Smith, Maria, additional, Vazquez-Pagan, Ana, additional, Flerlage, Tim, additional, Brigleb, Pamela H, additional, Meliopoulos, Victoria A., additional, Lindenbach, Brett D., additional, Cortez, Valerie, additional, Crawford, Jeremy Chase, additional, and Schultz-Cherry, Stacey, additional

Published
2023
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20. Virion Assembly and Release

Author

Lindenbach, Brett D., Aktories, Klaus, Series Editor, Compans, Richard W., Series Editor, Cooper, Max D., Series Editor, Galan, Jorge E., Series Editor, Gleba, Yuri Y., Series Editor, Honjo, Tasuku, Series Editor, Kawaoka, Yoshihiro, Series Editor, Koprowski, Hilary, Honorary Editor, Malissen, Bernard, Series Editor, Melchers, Fritz, Series Editor, Oldstone, Michael B. A., Series Editor, Rappuoli, Rino, Series Editor, Vogt, Peter K., Series Editor, and Bartenschlager, Ralf, editor

Published
2013
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28. Cellular Cofactors Affecting Hepatitis C Virus Infection and Replication

Author

Randall, Glenn, Panis, Maryline, Cooper, Jacob D., Tellinghuisen, Timothy L., Sukhodolets, Karen E., Pfeffer, Sebastien, Landthaler, Markus, Landgraf, Pablo, Kan, Sherry, Lindenbach, Brett D., Chien, Minchen, Weir, David B., Russo, James J., Ju, Jingyue, Brownstein, Michael J., Sheridan, Robert, Sander, Chris, Zavolan, Mihaela, Tuschl, Thomas, and Rice, Charles M.

Published
2007
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31. De novo emergence of a remdesivir resistance mutation during treatment of persistent SARS-CoV-2 infection in an immunocompromised patient: A case report

Author

Gandhi, Shiv, primary, Klein, Jonathan, additional, Robertson, Alexander, additional, Peña-Hernández, Mario A., additional, Lin, Michelle J, additional, Roychoudhury, Pavitra, additional, Lu, Peiwen, additional, Fournier, John, additional, Ferguson, David, additional, Mohamed Bakhash, Shah A., additional, Catherine Muenker, M., additional, Srivathsan, Ariktha, additional, Wunder, Elsio A., additional, Kerantzas, Nicholas, additional, Wang, Wenshuai, additional, Lindenbach, Brett, additional, Pyle, Anna, additional, Wilen, Craig B., additional, Ogbuagu, Onyema, additional, Greninger, Alexander L., additional, Iwasaki, Akiko, additional, Schulz, Wade L., additional, and Ko, Albert I., additional

Published
2021
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32. Optimization of Triarylpyridinone Inhibitors of the Main Protease of SARS-CoV-2 to Low-Nanomolar Antiviral Potency

Author

Zhang, Chun-Hui, primary, Spasov, Krasimir A., additional, Reilly, Raquel A., additional, Hollander, Klarissa, additional, Stone, Elizabeth A., additional, Ippolito, Joseph A., additional, Liosi, Maria-Elena, additional, Deshmukh, Maya G., additional, Tirado-Rives, Julian, additional, Zhang, Shuo, additional, Liang, Zhuobin, additional, Miller, Scott J., additional, Isaacs, Farren, additional, Lindenbach, Brett D., additional, Anderson, Karen S., additional, and Jorgensen, William L., additional

Published
2021
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33. Restriction of SARS-CoV-2 replication by targeting programmed −1 ribosomal frameshifting

Author

Sun, Yu, primary, Abriola, Laura, additional, Niederer, Rachel O., additional, Pedersen, Savannah F., additional, Alfajaro, Mia M., additional, Silva Monteiro, Valter, additional, Wilen, Craig B., additional, Ho, Ya-Chi, additional, Gilbert, Wendy V., additional, Surovtseva, Yulia V., additional, Lindenbach, Brett D., additional, and Guo, Junjie U., additional

Published
2021
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34. Identification of microRNAs of the herpesvirus family

Author

Pfeffer, Sébastien, Sewer, Alain, Lagos-Quintana, Mariana, Sheridan, Robert, Sander, Chris, Grässer, Friedrich A, van Dyk, Linda F, Ho, C Kiong, Shuman, Stewart, Chien, Minchen, Russo, James J, Ju, Jingyue, Randall, Glenn, Lindenbach, Brett D, Rice, Charles M, Simon, Viviana, Ho, David D, Zavolan, Mihaela, and Tuschl, Thomas

Published
2005
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35. Potent Noncovalent Inhibitors of the Main Protease of SARS-CoV-2 from Molecular Sculpting of the Drug Perampanel Guided by Free Energy Perturbation Calculations

Author

Zhang, Chun-Hui, primary, Stone, Elizabeth A., additional, Deshmukh, Maya, additional, Ippolito, Joseph A., additional, Ghahremanpour, Mohammad M., additional, Tirado-Rives, Julian, additional, Spasov, Krasimir A., additional, Zhang, Shuo, additional, Takeo, Yuka, additional, Kudalkar, Shalley N., additional, Liang, Zhuobin, additional, Isaacs, Farren, additional, Lindenbach, Brett, additional, Miller, Scott J., additional, Anderson, Karen S., additional, and Jorgensen, William L., additional

Published
2021
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37. Genome-wide CRISPR Screens Reveal Host Factors Critical for SARS-CoV-2 Infection

Author

Wei, Jin, primary, Alfajaro, Mia Madel, additional, DeWeirdt, Peter C., additional, Hanna, Ruth E., additional, Lu-Culligan, William J., additional, Cai, Wesley L., additional, Strine, Madison S., additional, Zhang, Shang-Min, additional, Graziano, Vincent R., additional, Schmitz, Cameron O., additional, Chen, Jennifer S., additional, Mankowski, Madeleine C., additional, Filler, Renata B., additional, Ravindra, Neal G., additional, Gasque, Victor, additional, de Miguel, Fernando J., additional, Patil, Ajinkya, additional, Chen, Huacui, additional, Oguntuyo, Kasopefoluwa Y., additional, Abriola, Laura, additional, Surovtseva, Yulia V., additional, Orchard, Robert C., additional, Lee, Benhur, additional, Lindenbach, Brett D., additional, Politi, Katerina, additional, van Dijk, David, additional, Kadoch, Cigall, additional, Simon, Matthew D., additional, Yan, Qin, additional, Doench, John G., additional, and Wilen, Craig B., additional

Published
2021
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38. Unravelling hepatitis C virus replication from genome to function

Author

Lindenbach, Brett D. and Rice, Charles M.

Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): Brett D. Lindenbach [1]; Charles M. Rice (corresponding author) [1] In the mid-1970s, it was noticed that the world's supply of blood was contaminated with an unidentified agent causing [...]

Published
2005
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43. Genome-wide CRISPR screen reveals host genes that regulate SARS-CoV-2 infection

Author

Wei, Jin, primary, Alfajaro, Mia Madel, additional, Hanna, Ruth E., additional, DeWeirdt, Peter C., additional, Strine, Madison S., additional, Lu-Culligan, William J., additional, Zhang, Shang-Min, additional, Graziano, Vincent R., additional, Schmitz, Cameron O., additional, Chen, Jennifer S., additional, Mankowski, Madeleine C., additional, Filler, Renata B., additional, Gasque, Victor, additional, de Miguel, Fernando, additional, Chen, Huacui, additional, Oguntuyo, Kasopefoluwa, additional, Abriola, Laura, additional, Surovtseva, Yulia V., additional, Orchard, Robert C., additional, Lee, Benhur, additional, Lindenbach, Brett, additional, Politi, Katerina, additional, van Dijk, David, additional, Simon, Matthew D., additional, Yan, Qin, additional, Doench, John G., additional, and Wilen, Craig B., additional

Published
2020
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47. Component A2 of methylcoenzyme M reductase system from Methanobacterium thermoautotrophicum deltaH: nucleotide sequence and functional expression by Escherichia coli

Author

Kuhner, Carla H., Lindenbach, Brett D., and Wolfe, Ralph S.

Subjects
Mercaptoethanol -- Genetic aspects, Methanobacteriaceae -- Genetic aspects, Escherichia coli -- Genetic aspects, Biological sciences
Abstract

The gene for component A2 of the methylcoenzyme M reductase system from Methanobacterium thermoautotrophicum deltaH was cloned and sequenced. The gene for A2, designated atwA, encodes an acidic protein of 59 kDa. It was demonstrated that functional A2 can be purified from Escherichia coli and that A2 has extensive homology to the ATP-binding domains of the ATP-binding cassette family of transport systems.

Published
1993

50. Restriction of SARS-CoV-2 replication by targeting programmed -1 ribosomal frameshifting.

Author

Yu Sun, Abriola, Laura, Niederer, Rachel O., Pedersen, Savannah F., Alfajaro, Mia M., Monteiro, Valter Silva, Wilen, Craig B., Ya-Chi Ho, Gilbert, Wendy V., Surovtseva, Yulia V., Lindenbach, Brett D., and Junjie U. Guo

Subjects
SARS-CoV-2, HIGH throughput screening (Drug development), COVID-19, VIRAL genes
Abstract

Translation of open reading frame 1b (ORF1b) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires a programmed -1 ribosomal frameshift (-1 PRF) promoted by an RNA pseudoknot. The extent to which SARS-CoV-2 replication may be sensitive to changes in -1 PRF efficiency is currently unknown. Through an unbiased, reporter-based high-throughput compound screen, we identified merafloxacin, a fluoroquinolone antibacterial, as a -1 PRF inhibitor for SARS-CoV-2. Frameshift inhibition by merafloxacin is robust to mutations within the pseudoknot region and is similarly effective on -1 PRF of other betacoronaviruses. Consistent with the essential role of -1 PRF in viral gene expression, merafloxacin impedes SARS-CoV-2 replication in Vero E6 cells, thereby providing proof-of-principle for targeting -1 PRF as a plausible and effective antiviral strategy for SARS-CoV-2 and other coronaviruses. [ABSTRACT FROM AUTHOR]

Published
2021
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