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1. The harms of promoting the lab leak hypothesis for SARS-CoV-2 origins without evidence.

Author

Alwine, James, Goodrum, Felicia, Banfield, Bruce, Bloom, David, Britt, William J, Broadbent, Andrew J, Campos, Samuel K, Casadevall, Arturo, Chan, Gary C, Cliffe, Anna R, Dermody, Terence, Duprex, Paul, Enquist, Lynn W, Frueh, Klaus, Geballe, Adam P, Gaglia, Marta, Goldstein, Stephen, Greninger, Alexander L, Gronvall, Gigi Kwick, Jung, Jae U, Kamil, Jeremy P, Lakdawala, Seema, Liu, Shan-Lu, Luftig, Micah, Moore, John P, Moscona, Anne, Neuman, Benjamin W, Nikolich, Janko Ž, O'Connor, Christine, Pekosz, Andrew, Permar, Sallie, Pfeiffer, Julie, Purdy, John, Rasmussen, Angela, Semler, Bert, Smith, Gregory A, Stein, David A, Van Doorslaer, Koenraad, Weller, Sandra K, Whelan, Sean PJ, and Yurochko, Andrew

Subjects
Agricultural, Veterinary and Food Sciences, Biological Sciences, Biomedical and Clinical Sciences, Emerging Infectious Diseases, Coronaviruses, Infectious Diseases, Life on Land, COVID-19, SARS-CoV-2, anti-science, lab leak, origin, pandemic, science advocacy, science policy, spillover, zoonosis, Agricultural and Veterinary Sciences, Medical and Health Sciences, Virology, Agricultural, veterinary and food sciences, Biological sciences, Biomedical and clinical sciences
Abstract

Science is humanity's best insurance against threats from nature, but it is a fragile enterprise that must be nourished and protected. The preponderance of scientific evidence indicates a natural origin for SARS-CoV-2. Yet, the theory that SARS-CoV-2 was engineered in and escaped from a lab dominates media attention, even in the absence of strong evidence. We discuss how the resulting anti-science movement puts the research community, scientific research, and pandemic preparedness at risk.

Published
2024

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

4. Virology under the Microscope-a Call for Rational Discourse.

Author

Goodrum, Felicia, Lowen, Anice C, Lakdawala, Seema, Alwine, James, Casadevall, Arturo, Imperiale, Michael J, Atwood, Walter, Avgousti, Daphne, Baines, Joel, Banfield, Bruce, Banks, Lawrence, Bhaduri-McIntosh, Sumita, Bhattacharya, Deepta, Blanco-Melo, Daniel, Bloom, David, Boon, Adrianus, Boulant, Steeve, Brandt, Curtis, Broadbent, Andrew, Brooke, Christopher, Cameron, Craig, Campos, Samuel, Caposio, Patrizia, Chan, Gary, Cliffe, Anna, Coffin, John, Collins, Kathleen, Damania, Blossom, Daugherty, Matthew, Debbink, Kari, DeCaprio, James, Dermody, Terence, Dikeakos, Jimmy, DiMaio, Daniel, Dinglasan, Rhoel, Duprex, W Paul, Dutch, Rebecca, Elde, Nels, Emerman, Michael, Enquist, Lynn, Fane, Bentley, Fernandez-Sesma, Ana, Flenniken, Michelle, Frappier, Lori, Frieman, Matthew, Frueh, Klaus, Gack, Michaela, Gaglia, Marta, Gallagher, Tom, Galloway, Denise, García-Sastre, Adolfo, Geballe, Adam, Glaunsinger, Britt, Goff, Stephen, Greninger, Alexander, Hancock, Meaghan, Harris, Eva, Heaton, Nicholas, Heise, Mark, Heldwein, Ekaterina, Hogue, Brenda, Horner, Stacy, Hutchinson, Edward, Hyser, Joseph, Jackson, William, Kalejta, Robert, Kamil, Jeremy, Karst, Stephanie, Kirchhoff, Frank, Knipe, David, Kowalik, Timothy, Lagunoff, Michael, Laimins, Laimonis, Langlois, Ryan, Lauring, Adam, Lee, Benhur, Leib, David, Liu, Shan-Lu, Longnecker, Richard, Lopez, Carolina, Luftig, Micah, Lund, Jennifer, Manicassamy, Balaji, McFadden, Grant, McIntosh, Michael, Mehle, Andrew, Miller, W Allen, Mohr, Ian, Moody, Cary, Moorman, Nathaniel, Moscona, Anne, Mounce, Bryan, Munger, Joshua, Münger, Karl, Murphy, Eain, Naghavi, Mojgan, Nelson, Jay, Neufeldt, Christopher, Nikolich, Janko, and O'Connor, Christine

Subjects
COVID-19, Coronavirus, DURC, Gain of function, SARS-CoV-2, biosafety, influenza, pandemic, vaccines, zoonosis, Infectious Diseases, Prevention, Vaccine Related, Immunization, Infection, Good Health and Well Being, Biological Sciences, Medical and Health Sciences, Microbiology
Abstract

Viruses have brought humanity many challenges: respiratory infection, cancer, neurological impairment and immunosuppression to name a few. Virology research over the last 60+ years has responded to reduce this disease burden with vaccines and antivirals. Despite this long history, the COVID-19 pandemic has brought unprecedented attention to the field of virology. Some of this attention is focused on concern about the safe conduct of research with human pathogens. A small but vocal group of individuals has seized upon these concerns - conflating legitimate questions about safely conducting virus-related research with uncertainties over the origins of SARS-CoV-2. The result has fueled public confusion and, in many instances, ill-informed condemnation of virology. With this article, we seek to promote a return to rational discourse. We explain the use of gain-of-function approaches in science, discuss the possible origins of SARS-CoV-2 and outline current regulatory structures that provide oversight for virological research in the United States. By offering our expertise, we - a broad group of working virologists - seek to aid policy makers in navigating these controversial issues. Balanced, evidence-based discourse is essential to addressing public concern while maintaining and expanding much-needed research in virology.

Published
2023

5. Nebulized fusion inhibitory peptide protects cynomolgus macaques from measles virus infection

Author

Reynard, Olivier, Gonzalez, Claudia, Dumont, Claire, Iampietro, Mathieu, Ferren, Marion, Le Guellec, Sandrine, Laurie, Lajoie, Mathieu, Cyrille, Carpentier, Gabrielle, Roseau, Georges, Bovier, Francesca T., Zhu, Yun, Le Pennec, Deborah, Montharu, Jérome, Addetia, Amin, Greninger, Alexander L., Alabi, Christopher A., Brisebard, Elise, Moscona, Anne, Vecellio, Laurent, Porotto, Matteo, and Horvat, Branka

Published
2022
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6. 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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9. Human parainfluenza virus evolution during lung infection of immunocompromised individuals promotes viral persistence

Author

Greninger, Alexander L., Rybkina, Ksenia, Lin, Michelle J., Drew-Bear, Jennifer, Marcink, Tara C., Shean, Ryan C., Makhsous, Negar, Boeckh, Michael, Harder, Olivia, Bovier, Francesca, Burstein, Shana R., Niewiesk, Stefan, Rima, Bert K., Porotto, Matteo, and Moscona, Anne

Subjects
Lung diseases -- Risk factors -- Diagnosis -- Care and treatment, Immunocompromised host -- Health aspects, Parainfluenza viruses -- Diagnosis -- Care and treatment -- Risk factors, Amino acids -- Analysis, Health care industry
Abstract

The capacity of respiratory viruses to undergo evolution within the respiratory tract raises the possibility of evolution under the selective pressure of the host environment or drug treatment. Long-term infections in immunocompromised hosts are potential drivers of viral evolution and development of infectious variants. We showed that intrahost evolution in chronic human parainfluenza virus 3 (HPIV3) infection in immunocompromised individuals elicited mutations that favored viral entry and persistence, suggesting that similar processes may operate across enveloped respiratory viruses. We profiled longitudinal HPIV3 infections from 2 immunocompromised individuals that persisted for 278 and 98 days. Mutations accrued in the HPIV3 attachment protein hemagglutinin-neuraminidase (HN), including the first in vivo mutation in HN's receptor binding site responsible for activating the viral fusion process. Fixation of this mutation was associated with exposure to a drug that cleaves host-cell sialic acid moieties. Longitudinal adaptation of HN was associated with features that promote viral entry and persistence in cells, including greater avidity for sialic acid and more active fusion activity in vitro, but not with antibody escape. Long-term infection thus led to mutations promoting viral persistence, suggesting that host-directed therapeutics may support the evolution of viruses that alter their biophysical characteristics to persist in the face of these agents in vivo., Introduction Human parainfluenza virus 3 (HPIV3) accounts for a large proportion of respiratory illness in humans, especially in children, the elderly, and immunocompromised individuals (1-9), yet there is currently no [...]

Published
2021
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11. SARS-CoV-2 infection and recovery in children: Distinct T cell responses in MIS-C compared to COVID-19

Author

Rybkina, Ksenia, primary, Bell, Joseph N., additional, Bradley, Marissa C., additional, Wohlbold, Teddy, additional, Scafuro, Marika, additional, Meng, Wenzhao, additional, Korenberg, Rebecca C., additional, Davis-Porada, Julia, additional, Anderson, Brett R., additional, Weller, Rachel J., additional, Milner, Joshua D., additional, Moscona, Anne, additional, Porotto, Matteo, additional, Luning Prak, Eline T., additional, Pethe, Kalpana, additional, Connors, Thomas J., additional, and Farber, Donna L., additional

Published
2023
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12. Chikungunya infection: de-linking replication from symptomatology reveals the central role of muscle

Author

Moscona, Anne

Subjects
Mosquitoes -- Health aspects, Tocilizumab -- Health aspects, Skeletal muscle -- Health aspects, Virus replication, Climate, Travelers, Arthralgia, Diseases, Health care industry
Abstract

Chikungunya virus (CHIKV) is an emerging arbovirus, endemic in many parts of the world, that is spread by travelers and adapts to new mosquito vectors that live in temperate climates. CHIKV replicates in many host tissues and initially causes a self-limiting febrile illness similar to dengue. However, in 30%-40% of cases, CHIKV also causes long-term painful and debilitating muscle and joint pain, the pathogenesis of which remains unknown. In this issue of the JCI, Lentscher et al. engineered a skeletal muscle-restricted CHIKV to show that while musculoskeletal disease requires viral replication in affected muscle, muscular pathology is mediated by host immunological factors. These findings de-link viral replication and disease symptoms, illuminate the virus-host interplay in CHIKV symptomatology, and raise the possibility that immune modulation is a therapeutic option. The results also highlight possible solutions to existing vaccine barriers and provide insights that may apply to other viral diseases., Chikungunya is a uniquely dangerous emerging virus Chikungunya virus (CHIKV) is a member of the Old World Alphavirus genus of the Togaviridae family. It is an arbovirus that causes widespread [...]

Published
2020
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13. Virology under the Microscope—a Call for Rational Discourse

Author

Goodrum, Felicia, primary, Lowen, Anice C., additional, Lakdawala, Seema, additional, Alwine, James, additional, Casadevall, Arturo, additional, Imperiale, Michael J., additional, Atwood, Walter, additional, Avgousti, Daphne, additional, Baines, Joel, additional, Banfield, Bruce, additional, Banks, Lawrence, additional, Bhaduri-McIntosh, Sumita, additional, Bhattacharya, Deepta, additional, Blanco-Melo, Daniel, additional, Bloom, David, additional, Boon, Adrianus, additional, Boulant, Steeve, additional, Brandt, Curtis, additional, Broadbent, Andrew, additional, Brooke, Christopher, additional, Cameron, Craig, additional, Campos, Samuel, additional, Caposio, Patrizia, additional, Chan, Gary, additional, Cliffe, Anna, additional, Coffin, John, additional, Collins, Kathleen, additional, Damania, Blossom, additional, Daugherty, Matthew, additional, Debbink, Kari, additional, DeCaprio, James, additional, Dermody, Terence, additional, Dikeakos, Jimmy, additional, DiMaio, Daniel, additional, Dinglasan, Rhoel, additional, Duprex, W. Paul, additional, Dutch, Rebecca, additional, Elde, Nels, additional, Emerman, Michael, additional, Enquist, Lynn, additional, Fane, Bentley, additional, Fernandez-Sesma, Ana, additional, Flenniken, Michelle, additional, Frappier, Lori, additional, Frieman, Matthew, additional, Frueh, Klaus, additional, Gack, Michaela, additional, Gaglia, Marta, additional, Gallagher, Tom, additional, Galloway, Denise, additional, García-Sastre, Adolfo, additional, Geballe, Adam, additional, Glaunsinger, Britt, additional, Goff, Stephen, additional, Greninger, Alexander, additional, Hancock, Meaghan, additional, Harris, Eva, additional, Heaton, Nicholas, additional, Heise, Mark, additional, Heldwein, Ekaterina, additional, Hogue, Brenda, additional, Horner, Stacy, additional, Hutchinson, Edward, additional, Hyser, Joseph, additional, Jackson, William, additional, Kalejta, Robert, additional, Kamil, Jeremy, additional, Karst, Stephanie, additional, Kirchhoff, Frank, additional, Knipe, David, additional, Kowalik, Timothy, additional, Lagunoff, Michael, additional, Laimins, Laimonis, additional, Langlois, Ryan, additional, Lauring, Adam, additional, Lee, Benhur, additional, Leib, David, additional, Liu, Shan-Lu, additional, Longnecker, Richard, additional, Lopez, Carolina, additional, Luftig, Micah, additional, Lund, Jennifer, additional, Manicassamy, Balaji, additional, McFadden, Grant, additional, McIntosh, Michael, additional, Mehle, Andrew, additional, Miller, W. Allen, additional, Mohr, Ian, additional, Moody, Cary, additional, Moorman, Nathaniel, additional, Moscona, Anne, additional, Mounce, Bryan, additional, Munger, Joshua, additional, Münger, Karl, additional, Murphy, Eain, additional, Naghavi, Mojgan, additional, Nelson, Jay, additional, Neufeldt, Christopher, additional, Nikolich, Janko, additional, O'Connor, Christine, additional, Ono, Akira, additional, Orenstein, Walter, additional, Ornelles, David, additional, Ou, Jing-hsiung, additional, Parker, John, additional, Parrish, Colin, additional, Pekosz, Andrew, additional, Pellett, Philip, additional, Pfeiffer, Julie, additional, Plemper, Richard, additional, Polyak, Stephen, additional, Purdy, John, additional, Pyeon, Dohun, additional, Quinones-Mateu, Miguel, additional, Renne, Rolf, additional, Rice, Charles, additional, Schoggins, John, additional, Roller, Richard, additional, Russell, Charles, additional, Sandri-Goldin, Rozanne, additional, Sapp, Martin, additional, Schang, Luis, additional, Schmid, Scott, additional, Schultz-Cherry, Stacey, additional, Semler, Bert, additional, Shenk, Thomas, additional, Silvestri, Guido, additional, Simon, Viviana, additional, Smith, Gregory, additional, Smith, Jason, additional, Spindler, Katherine, additional, Stanifer, Megan, additional, Subbarao, Kanta, additional, Sundquist, Wesley, additional, Suthar, Mehul, additional, Sutton, Troy, additional, Tai, Andrew, additional, Tarakanova, Vera, additional, tenOever, Benjamin, additional, Tibbetts, Scott, additional, Tompkins, Stephen, additional, Toth, Zsolt, additional, van Doorslaer, Koenraad, additional, Vignuzzi, Marco, additional, Wallace, Nicholas, additional, Walsh, Derek, additional, Weekes, Michael, additional, Weinberg, Jason, additional, Weitzman, Matthew, additional, Weller, Sandra, additional, Whelan, Sean, additional, White, Elizabeth, additional, Williams, Bryan, additional, Wobus, Christiane, additional, Wong, Scott, additional, and Yurochko, Andrew, additional

Published
2023
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14. Subnanometer structure of an enveloped virus fusion complex on viral surface reveals new entry mechanisms

Author

Marcink, Tara C., primary, Zipursky, Gillian, additional, Cheng, Wenjing, additional, Stearns, Kyle, additional, Stenglein, Shari, additional, Golub, Kate, additional, Cohen, Frances, additional, Bovier, Francesca, additional, Pfalmer, Daniel, additional, Greninger, Alexander L., additional, Porotto, Matteo, additional, des Georges, Amedee, additional, and Moscona, Anne, additional

Published
2023
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15. Intermediates in SARS-CoV-2 spike–mediated cell entry

Author

Marcink, Tara C., primary, Kicmal, Thomas, additional, Armbruster, Emily, additional, Zhang, Zhening, additional, Zipursky, Gillian, additional, Golub, Kate L., additional, Idris, Mohab, additional, Khao, Jonathan, additional, Drew-Bear, Jennifer, additional, McGill, Gael, additional, Gallagher, Tom, additional, Porotto, Matteo, additional, des Georges, Amédée, additional, and Moscona, Anne, additional

Published
2022
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18. Potency of Fusion-Inhibitory Lipopeptides against SARS-CoV-2 Variants of Concern

Author

Schmitz, Katharina S., Geers, Daryl, de Vries, Rory D., Bovier, T. Francesca, Mykytyn, Anna Z., Geurts van Kessel, Corine H., Haagmans, Bart L., Porotto, Matteo, de Swart, Rik L., Moscona, Anne, Schmitz, Katharina S., Geers, Daryl, de Vries, Rory D., Bovier, T. Francesca, Mykytyn, Anna Z., Geurts van Kessel, Corine H., Haagmans, Bart L., Porotto, Matteo, de Swart, Rik L., and Moscona, Anne

Abstract

The ability of SARS-CoV-2 to evolve in response to selective pressures poses a challenge to vaccine and antiviral efficacy. The S1 subunit of the spike (S) protein contains the receptor-binding domain and is therefore under selective pressure to evade neutralizing antibodies elicited by vaccination or infection. In contrast, the S2 subunit of S is only transiently exposed after receptor binding, which makes it a less efficient target for antibodies. As a result, S2 has a lower mutational frequency than S1. We recently described monomeric and dimeric SARS-CoV-2 fusion-inhibitory lipopeptides that block viral infection by interfering with S2 conformational rearrangements during viral entry. Importantly, a dimeric lipopeptide was shown to block SARS-CoV-2 transmission between ferrets in vivo. Because the S2 subunit is relatively conserved in newly emerging SARS-CoV-2 variants of concern (VOCs), we hypothesize that fusion-inhibitory lipopeptides are cross-protective against infection with VOCs. Here, we directly compared the in vitro efficacies of two fusion-inhibitory lipopeptides against VOC, in comparison with a set of seven postvaccination sera (two doses) and a commercial monoclonal antibody preparation. For the beta, delta, and omicron VOCs, it has been reported that convalescent and postvaccination sera are less potent in virus neutralization assays. Both fusion-inhibitory lipopeptides were equally effective against all five VOCs compared to ancestral virus, whereas postvaccination sera and therapeutic monoclonal antibody lost potency to newer VOCs, in particular to omicron BA.1 and BA.2. The neutralizing activity of the lipopeptides is consistent, and they can be expected to neutralize future VOCs based on their mechanism of action.

Published
2022

19. Repurposing an In Vitro Measles Virus Dissemination Assay for Screening of Antiviral Compounds

Author

Schmitz, Katharina S., Lange, Mona V., Gommers, Lennert, Handrejk, Kim, Porter, Danielle P., Alabi, Christopher A., Moscona, Anne, Porotto, Matteo, de Vries, Rory D., de Swart, Rik L., Schmitz, Katharina S., Lange, Mona V., Gommers, Lennert, Handrejk, Kim, Porter, Danielle P., Alabi, Christopher A., Moscona, Anne, Porotto, Matteo, de Vries, Rory D., and de Swart, Rik L.

Abstract

Measles virus (MV) is a highly contagious respiratory virus responsible for outbreaks associated with significant morbidity and mortality among children and young adults. Although safe and effective measles vaccines are available, the COVID-19 pandemic has resulted in vaccination coverage gaps that may lead to the resurgence of measles when restrictions are lifted. This puts individuals who cannot be vaccinated, such as young infants and immunocompromised individuals, at risk. Therapeutic interventions are complicated by the long incubation time of measles, resulting in a narrow treatment window. At present, the only available WHO-advised option is treatment with intravenous immunoglobulins, although this is not approved as standard of care. Antivirals against measles may contribute to intervention strategies to limit the impact of future outbreaks. Here, we review previously described antivirals and antiviral assays, evaluate the antiviral efficacy of a number of compounds to inhibit MV dissemination in vitro, and discuss potential application in specific target populations. We conclude that broadly reactive antivirals could strengthen existing intervention strategies to limit the impact of measles outbreaks.

Published
2022

20. Modeling Infection and Tropism of Human Parainfluenza Virus Type 3 in Ferrets

Author

Rijsbergen, Laurine C., Schmitz, Katharina S., Begeman, Lineke, Drew-Bear, Jennifer, Gommers, Lennert, Lamers, Mart M., Greninger, Alexander L., Haagmans, Bart L., Porotto, Matteo, de Swart, Rik L., Moscona, Anne, de Vries, Rory D., Rijsbergen, Laurine C., Schmitz, Katharina S., Begeman, Lineke, Drew-Bear, Jennifer, Gommers, Lennert, Lamers, Mart M., Greninger, Alexander L., Haagmans, Bart L., Porotto, Matteo, de Swart, Rik L., Moscona, Anne, and de Vries, Rory D.

Abstract

Human parainfluenza virus type 3 (HPIV-3) is a significant cause of lower respiratory tract infections, with the most severe disease in young infants, immunocompromised individuals, and the elderly. HPIV-3 infections are currently untreatable with licensed therapeutics, and prophylactic and therapeutic options are needed for patients at risk. To complement existing human airway models of HPIV-3 infection and develop an animal model to assess novel intervention strategies, we evaluated infection and transmission of HPIV-3 in ferrets. A well-characterized human clinical isolate (CI) of HPIV-3 engineered to express enhanced green fluorescent protein (rHPIV-3 CI-1-EGFP) was passaged on primary human airway epithelial cells (HAE) or airway organoids (AO) to avoid tissue culture adaptations. rHPIV3 CI-1-EGFP infection was assessed in vitro in ferret AO and in ferrets in vivo. Undifferentiated and differentiated ferret AO cultures supported rHPIV-3 CI-1-EGFP replication, but the ferret primary airway cells from AO were less susceptible and permissive than HAE. In vivo rHPIV-3 CI-1-EGFP replicated in the upper and lower airways of ferrets and targeted respiratory epithelial cells, olfactory epithelial cells, type I pneumocytes, and type II pneumocytes. The infection efficiently induced specific antibody responses. Taken together, ferrets are naturally susceptible to HPIV-3 infection; however, limited replication was observed that led to neither overt clinical signs nor ferret-to-ferret transmission. However, in combination with ferret AO, the ferret model of HPIV-3 infection, tissue tropism, and neutralizing antibodies complements human ex vivo lung models and can be used as a platform for prevention and treatment studies for this important respiratory pathogen. IMPORTANCE HPIV-3 is an important cause of pediatric disease and significantly impacts the elderly. Increasing numbers of immunocompromised patients suffer from HPIV-3 infections, often related to problems with v

Published
2022

21. Absence of COVID-19-associated changes in plasma coagulation proteins and pulmonary thrombosis in the ferret model

Author

Kreft, Iris C., Winiarczyk, Roy R.A., Tanis, Fric J., van der Zwaan, Carmen, Schmitz, Katharina S., Hoogendijk, Arie J., de Swart, Rik L., Moscona, Anne, Porotto, Matteo, Salvatori, Daniela C.F., de Vries, Rory D., de Maat, Moniek P.M., van den Biggelaar, Maartje, van Vlijmen, Bart J.M., Kreft, Iris C., Winiarczyk, Roy R.A., Tanis, Fric J., van der Zwaan, Carmen, Schmitz, Katharina S., Hoogendijk, Arie J., de Swart, Rik L., Moscona, Anne, Porotto, Matteo, Salvatori, Daniela C.F., de Vries, Rory D., de Maat, Moniek P.M., van den Biggelaar, Maartje, and van Vlijmen, Bart J.M.

Abstract

Background: Many patients who are diagnosed with coronavirus disease 2019 (COVID-19) suffer from venous thromboembolic complications despite the use of stringent anticoagulant prophylaxis. Studies on the exact mechanism(s) underlying thrombosis in COVID-19 are limited as animal models commonly used to study venous thrombosis pathophysiology (i.e. rats and mice) are naturally not susceptible to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Ferrets are susceptible to SARS-CoV-2 infection, successfully used to study virus transmission, and have been previously used to study activation of coagulation and thrombosis during influenza virus infection. Objectives: This study aimed to explore the use of (heat-inactivated) plasma and lung material from SARS-CoV-2-inoculated ferrets studying COVID-19-associated changes in coagulation and thrombosis. Material and methods: Histology and longitudinal plasma profiling using mass spectrometry-based proteomics approach was performed. Results: Lungs of ferrets inoculated intranasally with SARS-CoV-2 demonstrated alveolar septa that were mildly expanded by macrophages, and diffuse interstitial histiocytic pneumonia. However, no macroscopical or microscopical evidence of vascular thrombosis in the lungs of SARS-CoV-2-inoculated ferrets was found. Longitudinal plasma profiling revealed minor differences in plasma protein profiles in SARS-CoV-2-inoculated ferrets up to 2 weeks post-infection. The majority of plasma coagulation factors were stable and demonstrated a low coefficient of variation. Conclusions: We conclude that while ferrets are an essential and well-suited animal model to study SARS-CoV-2 transmission, their use to study SARS-CoV-2-related changes relevant to thrombotic disease is limited.

Published
2022

22. Modeling Infection and Tropism of Human Parainfluenza Virus Type 3 in Ferrets

Author

Rijsbergen, Laurine C., primary, Schmitz, Katharina S., additional, Begeman, Lineke, additional, Drew-Bear, Jennifer, additional, Gommers, Lennert, additional, Lamers, Mart M., additional, Greninger, Alexander L., additional, Haagmans, Bart L., additional, Porotto, Matteo, additional, de Swart, Rik L., additional, Moscona, Anne, additional, and de Vries, Rory D., additional

Published
2022
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24. A Broad-Spectrum Antiviral Targeting Entry of Enveloped Viruses

Author

Wolf, Mike C., Freiberg, Alexander N., Zhang, Tinghu, Akyol-Ataman, Zeynep, Grock, Andrew, Hong, Patrick W., Li, Jianrong, Watson, Natalya F., Fang, Angela Q., Aguilar, Hector C., Porotto, Matteo, Honko, Anna N., Damoiseaux, Robert, Miller, John P., Woodson, Sara E., Chantasirivisal, Steven, Fontanes, Vanessa, Negrete, Oscar A., Krogstad, Paul, Dasgupta, Asim, Moscona, Anne, Hensley, Lisa E., Whelan, Sean P., Faull, Kym F., Holbrook, Michael R., Jung, Michael E., Lee, Benhur, and Palese, Peter

Published
2010
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27. Rapid and Flexible Platform To Assess Anti-SARS-CoV-2 Antibody Neutralization and Spike Protein-Specific Antivirals

Author

Stelitano, Debora, primary, Weisberg, Stuart P., additional, Goldklang, Monica P., additional, Zhu, Yun, additional, Bovier, Francesca T., additional, Kalantarov, Gavreel F., additional, Greco, Giuseppe, additional, Decimo, Didier, additional, Franci, Gianluigi, additional, Cennamo, Michele, additional, Portella, Giuseppe, additional, Galdiero, Massimiliano, additional, Mathieu, Cyrille, additional, Horvat, Branka, additional, Trakht, Ilya N., additional, Moscona, Anne, additional, Whitt, Michael A., additional, and Porotto, Matteo, additional

Published
2021
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28. Molecular Features of the Measles Virus Viral Fusion Complex That Favor Infection and Spread in the Brain

Author

Mathieu, Cyrille, primary, Bovier, Francesca T., additional, Ferren, Marion, additional, Lieberman, Nicole A. P., additional, Predella, Camilla, additional, Lalande, Alexandre, additional, Peddu, Vikas, additional, Lin, Michelle J., additional, Addetia, Amin, additional, Patel, Achchhe, additional, Outlaw, Victor, additional, Corneo, Barbara, additional, Dorrello, N. Valerio, additional, Briese, Thomas, additional, Hardie, Diana, additional, Horvat, Branka, additional, Moscona, Anne, additional, Greninger, Alexander L., additional, and Porotto, Matteo, additional

Published
2021
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29. Inhibition of Coronavirus Entry In Vitro and Ex Vivo by a Lipid-Conjugated Peptide Derived from the SARS-CoV-2 Spike Glycoprotein HRC Domain

Author

Outlaw, Victor K., primary, Bovier, Francesca T., additional, Mears, Megan C., additional, Cajimat, Maria N., additional, Zhu, Yun, additional, Lin, Michelle J., additional, Addetia, Amin, additional, Lieberman, Nicole A. P., additional, Peddu, Vikas, additional, Xie, Xuping, additional, Shi, Pei-Yong, additional, Greninger, Alexander L., additional, Gellman, Samuel H., additional, Bente, Dennis A., additional, Moscona, Anne, additional, and Porotto, Matteo, additional

Published
2020
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31. In vivo antiviral host transcriptional response to SARS-CoV-2 by viral load, sex, and age

Author

Lieberman, Nicole A. P., primary, Peddu, Vikas, additional, Xie, Hong, additional, Shrestha, Lasata, additional, Huang, Meei-Li, additional, Mears, Megan C., additional, Cajimat, Maria N., additional, Bente, Dennis A., additional, Shi, Pei-Yong, additional, Bovier, Francesca, additional, Roychoudhury, Pavitra, additional, Jerome, Keith R., additional, Moscona, Anne, additional, Porotto, Matteo, additional, and Greninger, Alexander L., additional

Published
2020
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33. Identification of a novel deltavirus in Boa Constrictors

Author

Moscona, Anne, Moscona, A ( Anne ), Hetzel, Udo; https://orcid.org/0000-0001-9142-560X, Szirovicza, Leonóra; https://orcid.org/0000-0003-1528-044X, Smura, Teemu; https://orcid.org/0000-0002-9187-3151, Prähauser, Barbara, Vapalahti, Olli; https://orcid.org/0000-0003-2270-6824, Kipar, Anja; https://orcid.org/0000-0001-7289-3459, Hepojoki, Jussi; https://orcid.org/0000-0001-5699-214X, Moscona, Anne, Moscona, A ( Anne ), Hetzel, Udo; https://orcid.org/0000-0001-9142-560X, Szirovicza, Leonóra; https://orcid.org/0000-0003-1528-044X, Smura, Teemu; https://orcid.org/0000-0002-9187-3151, Prähauser, Barbara, Vapalahti, Olli; https://orcid.org/0000-0003-2270-6824, Kipar, Anja; https://orcid.org/0000-0001-7289-3459, and Hepojoki, Jussi; https://orcid.org/0000-0001-5699-214X

Abstract

Hepatitis D virus (HDV) forms the genus Deltavirus unassigned to any virus family. HDV is a satellite virus and needs hepatitis B virus (HBV) to make infectious particles. Deltaviruses are thought to have evolved in humans, since for a long time, they had not been identified elsewhere. Herein we report, prompted by the recent discovery of an HDV-like agent in birds, the identification of a deltavirus in snakes (Boa constrictor) designated snake HDV (sHDV). The circular 1,711-nt RNA genome of sHDV resembles human HDV (hHDV) in its coding strategy and size. We discovered sHDV during a metatranscriptomic study of brain samples of a Boa constrictor breeding pair with central nervous system signs. Applying next-generation sequencing (NGS) to brain, blood, and liver samples from both snakes, we did not find reads matching hepadnaviruses. Sequence comparison showed the snake delta antigen (sHDAg) to be 55% and 37% identical to its human and avian counterparts. Antiserum raised against recombinant sHDAg was used in immunohistology and demonstrated a broad viral target cell spectrum, including neurons, epithelial cells, and leukocytes. Using RT-PCR, we also detected sHDV RNA in two juvenile offspring and in a water python (Liasis mackloti savuensis) in the same snake colony, potentially indicating vertical and horizontal transmission. Screening of 20 randomly selected boas from another breeder by RT-PCR revealed sHDV infection in three additional snakes. The observed broad tissue tropism and the failure to detect accompanying hepadnavirus suggest that sHDV could be a satellite virus of a currently unknown enveloped virus. IMPORTANCE So far, the only known example of deltaviruses is the hepatitis delta virus (HDV). HDV is speculated to

Published
2019

34. Measles Virus Bearing Measles Inclusion Body Encephalitis-Derived Fusion Protein Is Pathogenic after Infection via the Respiratory Route

Author

Mathieu, Cyrille, primary, Ferren, Marion, additional, Jurgens, Eric, additional, Dumont, Claire, additional, Rybkina, Ksenia, additional, Harder, Olivia, additional, Stelitano, Debora, additional, Madeddu, Silvia, additional, Sanna, Giuseppina, additional, Schwartz, Dayna, additional, Biswas, Sudipta, additional, Hardie, Diana, additional, Hashiguchi, Takao, additional, Moscona, Anne, additional, Horvat, Branka, additional, Niewiesk, Stefan, additional, and Porotto, Matteo, additional

Published
2019
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35. Analysis of a Subacute Sclerosing Panencephalitis Genotype B3 Virus from the 2009-2010 South African Measles Epidemic Shows That Hyperfusogenic F Proteins Contribute to Measles Virus Infection in the Brain

Author

Angius, Fabrizio, primary, Smuts, Heidi, additional, Rybkina, Ksenia, additional, Stelitano, Debora, additional, Eley, Brian, additional, Wilmshurst, Jo, additional, Ferren, Marion, additional, Lalande, Alexandre, additional, Mathieu, Cyrille, additional, Moscona, Anne, additional, Horvat, Branka, additional, Hashiguchi, Takao, additional, Porotto, Matteo, additional, and Hardie, Diana, additional

Published
2019
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36. Antiviral activity of gliotoxin, gentian violet and brilliant green against Nipah and Hendra virus in vitro

Author

Meyer Adam G, Porotto Matteo, Rootes Christina L, Lo Michael K, Sganga Michael L, Aljofan Mohamad, Saubern Simon, Moscona Anne, and Mungall Bruce A

Subjects
Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background Using a recently described monolayer assay amenable to high throughput screening format for the identification of potential Nipah virus and Hendra virus antivirals, we have partially screened a low molecular weight compound library (>8,000 compounds) directly against live virus infection and identified twenty eight promising lead molecules. Initial single blind screens were conducted with 10 μM compound in triplicate with a minimum efficacy of 90% required for lead selection. Lead compounds were then further characterised to determine the median efficacy (IC50), cytotoxicity (CC50) and the in vitro therapeutic index in live virus and pseudotype assay formats. Results While a number of leads were identified, the current work describes three commercially available compounds: brilliant green, gentian violet and gliotoxin, identified as having potent antiviral activity against Nipah and Hendra virus. Similar efficacy was observed against pseudotyped Nipah and Hendra virus, vesicular stomatitis virus and human parainfluenza virus type 3 while only gliotoxin inhibited an influenza A virus suggesting a non-specific, broad spectrum activity for this compound. Conclusion All three of these compounds have been used previously for various aspects of anti-bacterial and anti-fungal therapy and the current results suggest that while unsuitable for internal administration, they may be amenable to topical antiviral applications, or as disinfectants and provide excellent positive controls for future studies.

Published
2009
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38. Unity in diversity: Shared mechanism of entry among paramyxoviruses

Author

Palgen, Jean-Louis, Jurgens, Eric M, Moscona, Anne, Porotto, Matteo, Palermo, Laura M., Palgen, Jean-Loui, Jurgens, Eric M, Moscona, Anne, Porotto, Matteo, and Palermo, Laura M.

Subjects
Animal, viruses, Viral entry, Receptors, Cell Surface, Virus Internalization, Article, Fusion machinery, Viral Proteins, Paramyxoviridae, Receptor-binding protein, Viral Protein, Animals, Humans, Glycoprotein, Fusion protein, Human, Glycoproteins, Protein Binding
Abstract

The Paramyxoviridae family includes many viruses that are pathogenic in humans, including parainfluenza viruses, measles virus, respiratory syncytial virus, and the emerging zoonotic Henipaviruses. No effective treatments are currently available for these viruses, and there is a need for efficient antiviral therapies. Paramyxoviruses enter the target cell by binding to a cell surface receptor and then fusing the viral envelope with the target cell membrane, allowing the release of the viral genome into the cytoplasm. Blockage of these crucial steps prevents infection and disease. Binding and fusion are driven by two virus-encoded glycoproteins, the receptor-binding protein and the fusion protein, that together form the viral "fusion machinery." The development of efficient antiviral drugs requires a deeper understanding of the mechanism of action of the Paramyxoviridae fusion machinery, which is still controversial. Here, we review recent structural and functional data on these proteins and the current understanding of the mechanism of the paramyxovirus cell entry process.

Published
2014

45. Influenza advice

Author

Moscona, Anne

Subjects
Influenza -- Care and treatment, Influenza vaccines -- Usage, Business, Business, regional, FluMist (Vaccine) -- Usage
Abstract

Everyone should definitely get a flu shot, and the Centers for Disease Control say sufficient vaccine should be available. But if you can't get one at work and your doctor [...]

Published
2005

49. Study of the Impact of Oseltamivir on the Risk for Pneumonia and Other Outcomes of Influenza, 2000–2005

Author

Peters, Patrick H., Moscona, Anne, Schulman, Kathy L., and Barr, Charles E.

Subjects
Adult, Male, Departments, Adolescent, Infant, Pneumonia, Middle Aged, Antiviral Agents, Cohort Studies, Young Adult, Oseltamivir, Treatment Outcome, Risk Factors, Child, Preschool, Influenza, Human, Humans, Female, Child, Aged, Retrospective Studies
Abstract

Influenza results in large numbers of secondary complications and hospitalizations.To assess the impact of oseltamivir on influenza-related complications and hospitalizations by analyzing health insurance claims data for 6 influenza seasons.A retrospective cohort study utilizing claims data from the 2000-2005 influenza seasons.Claims data were obtained from Thomson Healthcare MarketScan Research Databases.Patients prescribed oseltamivir within 1 day of influenza diagnosis were compared to those prescribed no antiviral therapy (controls).Frequencies of pneumonia, other respiratory illnesses, and otitis media, and rates of hospitalization, were compared for the oseltamivir and no antiviral groups. Expenditure was also analyzed. Relative risk (RR) for each outcome was assessed using Cox proportional hazards regression.Overall, 31,674 patients received oseltamivir and were propensity matched to patients with no antiviral prescription. Oseltamivir reduced the risk of diagnosis of pneumonia by 15% (RR 0.85, 95% confidence interval [CI] 0.73, 0.98), other respiratory illnesses by 20% (RR 0.80, 95% CI: 0.76, 0.83), and otitis media and its complications by 31% (RR 0.69, 95% CI: 0.61, 0.79). The greatest reductions in pneumonia risk, of 57% and 52%, were observed for children aged 6-12 years (RR 0.43, 95% CI: 0.26, 0.71) and 1-2 years (RR 0.48, 95% CI: 0.24, 0.99), respectively. Overall, hospitalization rates were reduced by 38% (RR 0.62, 95% CI: 0.52, 0.74) in the oseltamivir group compared with the no antiviral group. Total adjusted expenditures in the oseltamivir and no antiviral groups were not significantly different.Oseltamivir reduced the relative risk of influenza-related complications and hospitalization when prescribed immediately upon presentation of influenza.

Published
2008

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